CHAPTER 25

Neurocognitive Disorders André Strydom Mark H. Fleisher Shoumitro Deb Howard Ring Lucille Esralew Karen Dodd Tamara al Janab Jullian Trollor Sarah L. Whitwham

SM-5 replaced the terminology of the demen- panied by a change in cognition. The disturbance tias with a characterization of these neurode- develops over a short period of time, tends to fluc- Dgenerative disorders as neurocognitive disor- tuate during the course of the day, and is usually a ders. Throughout this chapter, the term “dementia” consequence of a medical condition, substance in- is avoided and the presentation and diagnosis of the toxication or withdrawal, or a medication at toxic neurocognitive disorders are discussed. In this chap- or even therapeutic doses. ter, we review the diagnosis of the disorders and con- The essential feature of a major neurocognitive sider how they are applied. We then go on to examine disorder is the development of multiple cognitive the etiology and pathology and to suggest changes deficits that are severe enough to cause impairment necessary to the diagnostic criteria for the disorders in daily functioning and represent a decline from a in people with intellectual disabilities. previous level of functioning. Neurocognitive Disorders Summary of DSM-5 Criteria The neurocognitive disorders (known as Dementia, Review of Diagnostic Criteria Delirium, Amnestic, and Other Cognitive Disorders in The disorders in this section concern a clinically DSM-IV-TR) comprise delirium, and major and mild significant acquired deficit in cognition that results neurocognitive disorder (NCD), divided into etiolog- in a significant decline from a previous level of func- ical subtypes. DSM-5 introduces the terms “major” tioning. They include delirium, major neurocognitive and “mild neurocognitive disorder” to indicate sever- disorder (dementia), and mild neurocognitive disor- ity of the impairment. The term “dementia” is avoided der. The underlying etiology varies among individu- in the DSM-5 criteria but may still be used where phy- als, but in the case of major neurocognitive disorder sicians and patients are accustomed to this term. The (dementia), several subtypes have been recognised. term “neurocognitive disorder” is often preferred, Delirium is commonly seen in general medical especially for conditions affecting younger adults. hospitals (American Psychiatric Association, 2006). Neurocognitive disorder is also seen as broader and The essential feature of delirium is an acquired and encompasses disorders included under “Amnestic usually acute disturbance of consciousness accom- Disorders” in DSM-IV-TR. 574 DM-ID-2 Textbook

Delirium medication taken as prescribed. Specific medi- cation category should be coded for. Review of Diagnostic Criteria ■ Delirium due to Another Medical A disturbance in attention, awareness, and Condition cognition/perception that develops over a short There is evidence that the disturbance may be period of time (less than a few days) and is like- attributable to another medical condition. The ly a direct physiological consequence of anoth- name of the other medical condition should be er medical condition or substance or is due to included in the name of the delirium (e.g. 293.0 multiple etiologies and not better explained by [F05]: delirium due to hepatic encephalopathy). a developing or established neurocognitive dis- The other medical condition should also be cod- order. The clinician should specify if the deliri- ed and listed separately immediately before the um is acute or persistent and if the individual is delirium. hyper-/hypoactive or has a mixed level of activ- ity. In hospital settings, delirium usually lasts ■ Delirium due to Multiple Etiologies about a week, but it may have a more prolonged There is evidence that the disturbance may be course in some individuals. The hyperactive attributable to multiple etiologies. Multiple sep- state may be more common (or more frequent- arate codes should be used in the same style as ly recognized) and is typically associated with delirium due to another medical condition. substance- or medication-related delirium. The There are also categories for other specified hypoactive state is more commonly recognized delirium and unspecified delirium. Other speci- in older adults. Delirium is frequently accom- fied delirium should be used when it is clinically panied by disturbances in the sleep-wake cy- significant but doesn’t otherwise meet the full cle and emotional/behavioral disturbances. criteria for delirium (e.g., attenuated delirium There is additionally often generalized slowing syndrome). The clinician should specify the on electroencephalography (EEG) recordings reason that the presentation does not meet the (or, occasionally, abnormally fast activity) al- criteria for the general diagnosis of delirium. though EEG is insufficiently sensitive or specif- Unspecified delirium can be used when the cli- ic enough for diagnostic use for delirium. nician is unable to specify the reason the pre- Delirium should be specified according to its sentation does not meet the criteria for the gen- etiological sub-type: eral diagnosis of delirium, such as when there is insufficient information available about the ■ Substance-Intoxication Delirium patient or the patient is previously unknown. This diagnosis should be made instead of substance intoxication when a disturbance in Major and Mild Neurocognitive Disorders attention and awareness that has developed over a short period of time predominates in Review of Diagnostic Criteria the clinical presentation and the disturbance is Major Neurocognitive disorder can be distin- sufficiently severe to warrant clinical attention. guished from mild Neurocognitive disorder by Coding is done for specific substance intoxica- the severity of the cognitive decline and the im- tion-related delirium. pact the symptoms have on the individual’s abil- ■ Substance-Withdrawal Delirium ity to carry out his or her daily living activities. Symptoms as above, but etiology of the con- To meet the diagnostic criteria for an Neu- dition is related to substance withdrawal rather rocognitive disorder, individuals must present than substance use. Coding is done for specific with significant (major Neurocognitive disor- substance withdrawal-related delirium. der) or modest (mild Neurocognitive disorder) cognitive decline in one or more domains (in- ■ Medication-Induced Delirium cluding complex attention, executive function, A disturbance in attention, awareness and learning and memory, language, perceptual-mo- cognition that develops as a consequence of a tor, or social cognition). There should be prior Chapter 25 Neurocognitive Disorders 575 concern that there has been a significant (ma- there is evidence of the presence of a known jor) or mild (mild) decline in cognitive function, pathogenic mutation from genetic testing or which is evidenced by substantial (major) or family history. If no such evidence is available, modest (mild) impairment in cognitive perfor- possible Alzheimer’s disease may be diagnosed mance (preferably evidenced by a standardized if there is a clear evidence of decline in learning cognitive test). The deficits should not occur ex- and memory, the cognitive decline is steadily clusively in the context of delirium and should progressive and gradual, and there is no evi- not be better explained by another mental dis- dence of mixed etiology order. For a diagnosis of mild neurocognitive Psychological and behavioral manifestations disorder, the cognitive decline should not in- of Alzheimer’s disease are very commonly ob- terfere with everyday life. For major neurocog- served in patients upon presentation and, even nitive disorder, the symptoms must interfere at the mild stage, depression and/or apathy are with independence in everyday activities. The often seen, and coding includes the presence of clinician must specify the severity of the symp- behavioral disturbance. Common behavioral/ toms for major neurocognitive disorder and psychological features in major Neurocognitive whether there are any behavioral disturbances disorder due to Alzheimer’s disease are psycho- with both mild and major neurocognitive disor- sis, irritability, agitation, combativeness, and der. In addition to cognitive decline, psychosis, wandering in the moderately severe stage with mood disturbances, agitation, apathy, and other gait disturbance, dysphagia, incontinence, my- behavioral symptoms are frequently observed. oclonus, and seizures frequently being observed The neurocognitive disorders are sub-clas- in the later stages. Cortical atrophy, amyloid-pre- sified according to etiology/pathology as fol- dominant neuritic plaques, and tau-predominant lows, and several include the option to specify neurofibrillary tangles are characteristic of Alz- whether or not they occur with behavioral dis- heimer’s disease and may be observed through turbance: neuroimaging or through post mortem histopa- thology. Coding is done for the certainty of the ■ Alzheimer’s Disease presence of Alzheimer’s disease. Mild or major neurocognitive disorder due to Alzheimer’s disease is diagnosed where there is ■ Frontotemporal Lobar Degeneration gradual progression of cognitive deficits in one Major or mild frontotemporal neurocognitive or more domains (for major Neurocognitive dis- disorder is diagnosed when there is either a pro- order, two or more domains must be impaired) gressive behavioral problem (including three or and the symptoms are not better explained more symptoms including behavioral disinhibi- by cerebrovascular disease, another neurode- tion, apathy or inertia, loss of sympathy or em- generative disorder, the use of a substance, or pathy, perseverative, stereotyped or ritualistic another mental, neurological, or systemic dis- behavior, and hyperorality or dietary changes) order. Criteria needs to be met also for either or a progressive language problem (a prominent probable or possible Alzheimer’s disease as decline in language ability, speech production, follows: Major Neurocognitive disorder due word-finding, grammar, or word-comprehen- to probable Alzheimer’s disease may be diag- sion). nosed where there is evidence of the presence The language variant of frontotemporal lobar of a known pathogenic mutation, or there is degeneration comprises three types: seman- clear evidence of a steadily progressive decline tic, agrammatic/nonfluent, and logopenic. The in learning and memory and at least one other cognitive deficit is relatively sparing of learning cognitive domain and no evidence of mixed eti- and memory and perceptual-motor function and ology; otherwise possible Alzheimer’s disease should not be better explained by cerebrovas- should be diagnosed. cular disease, another neurodegenerative disor- Mild Neurocognitive disorder due to Alzhei- der, the use of a substance, or another mental, mer’s disease may be diagnosed as probable if neurological, or systemic disorder. 576 DM-ID-2 Textbook

If there is evidence of known pathogenic sis may also be observed. Coding is done for the mutation from either family history or genetic certainty of the presence of major or mild neu- testing or there is evidence of disproportion- rocognitive disorder with Lewy bodies and the ate involvement of the frontal and/or temporal presence/absence of behavioral disturbances. lobes from neuroimaging, a diagnosis of prob- ■ Vascular Disease able frontotemporal lobar degeneration can be made. Possible frontotemporal lobar degener- Major or mild vascular neurocognitive disor- ation should be diagnosed otherwise. Patients der should be diagnosed in individuals whose may present with both the behavioral and the clinical features are consistent with a vascular language variant of frontotemporal lobar de- etiology (suggested by cognitive deficits with an generation concurrently, and coding includes a onset following a cerebrovascular event or de- system for indicating the presence of behavioral cline in complex attention (including process- disturbance. Extrapyramidal features, features ing speed) and frontal-executive functioning, of motor neurone disease, or visual hallucina- and where there is evidence of cerebrovascular tions may be apparent in some cases. disease from physical examination, history, and/or neuroimaging. ■ Lewy Body Disease Probable vascular neurocognitive disorder Major or mild neurocognitive disorder with should be diagnosed if one of the following is Lewy bodies should be diagnosed in individuals present (otherwise possible vascular neuro- presenting with the following core diagnostic cognitive disorder should be diagnosed): Cere- features: Fluctuating cognition with pronounced brovascular disease is supported by neuroim- variations in attention and alertness; recurrent aging, the symptoms are temporally related to vivid visual hallucinations; spontaneous fea- a cerebrovascular event, or both clinical and tures of Parkinsonism (with onset after the de- genetic evidence of cerebrovascular disease is velopment of cognitive decline). Suggestive diag- present. Personality and mood changes, lack of nostic features are fulfilling the criteria for REM initiative, depression, and emotional lability are sleep behavior disorder and severe neuroleptic often present. In older adults with progressive sensitivity. small vessel ischemic disease, depression, psy- For probable major or mild neurocognitive chomotor slowing and executive dysfunction disorder with Lewy bodies, the individual must are common. Coding is done for the certainty present with two core features, or one sugges- of the presence of vascular neurocognitive dis- tive feature and with one or more core features. order and the presence/absence of behavioral For possible major or mild neurocognitive dis- disturbances. order with Lewy bodies, the individual has only ■ one core feature, or one or more suggestive Traumatic Brain Injury features. The symptoms should not be better Major or mild neurocogntive disorder due to explained by cerebrovascular disease, anoth- traumatic brain injury should be diagnosed in er neurodegenerative disease, the effects of a individuals where there is evidence of a trau- substance, or another mental, neurological, or matic brain injury and loss of consciousness, systemic disorder. post-traumatic amnesia, disorientation and A diagnosis of mild neurocognitive disorder confusion, or other neurological signs. The dis- with Lewy bodies should be made when the order must present immediately after the brain cognitive and functional symptoms presenting injury or immediately after regaining conscious- are not sufficiently severe to warrant a diagno- ness and must persist beyond the acute post-in- sis of a major disorder. People with neurocog- jury period. Individuals frequently present with nitive disorder with Lewy bodies frequently re- emotional and behavioral disturbances. Coding port repeated falls and syncope and transient is done for behavioral disturbances, skull frac- loss of consciousness. Dysfunction of the auto- ture and loss of consciousness, and the severity nomic nervous system and features of psycho- of the neurocognitive disorder should be rated, Chapter 25 Neurocognitive Disorders 577 but not the severity of the underlying traumatic commonly observed in individuals with neuro- brain injury. cognitive disorder due to Parkinson’s disease include apathy, mood disturbances, psychotic ■ Substance/Medication Use symptoms, personality changes and sleep prob- Substance- or medication-induced major or lems. Coding is done for the presence/absence minor neurocognitive disorder should be di- of behavioral disturbances. agnosed in individuals presenting with neuro- cognitive impairments that do not occur exclu- ■ Huntington’s Disease sively during the course of delirium and persist Major or mild neurocognitive disorder due to beyond the ordinary course of intoxication and Huntington’s disease should be diagnosed in in- (acute) withdrawal. The substance and/or med- dividuals presenting with progressive cognitive ication must be capable of producing the defi- deficits with established Huntington’s disease cits and the temporal course of the symptoms (or at risk from family history) and where the should be consistent with substance and/or symptoms are not better explained by another medication use. Coding is done for substance, diagnosis. Other features commonly observed abstinence or intoxication state, and severity in individuals with Neurocognitive disorder and persistence can be specified. due to Huntington’s disease include mood dis- ■ HIV Infection turbances, obsessive-compulsive symptoms, apathy, and, occasionally, psychotic symptoms. Major or mild neurocognitive disorder due to Coding is done for the presence/absence of be- HIV infection should be diagnosed in individuals havioral disturbances. presenting with cognitive impairments and docu- mented infection with HIV. The symptoms should ■ Another Medical Condition not be attributable to any other medical condition A number of medical conditions can cause and should not be explained by another mental neurocognitive impairments. Individuals diag- disorder. Major or mild Neurocognitive disorder nosed with major or mild neurocognitive dis- is more common in individuals testing HIV posi- order due to another medical condition should tive who had had prior episodes of severe immu- present with evidence (through history, physical nosuppression, high viral loads in the cerebro- examination, etc.) that the deficits are a patho- spinal fluid, and anemia and hypoalbuminemia. physiological consequence of another medical Coding is done for behavioral disturbances. condition (excluding those already covered in ■ Prion Disease the section in the DSM-5). Major or mild neurocognitive disorder due to ■ Multiple Etiologies prion disease should be diagnosed in individ- The diagnosis is as above although the etiol- uals with progressive neurocognitive deficits ogy is presumed to arise from multiple condi- with motor features of prion disease (such as tions and/or events, excluding substance use. myoclonus or ataxia) or biomarker evidence There is also an unspecified neurocognitive and where the symptoms cannot be explained disorder category, to classify neurocognitive by another medical or mental disorder. Coding disorders where there is insufficient informa- is done for the presence/absence of behavioral tion and/or the precise etiology of the deficits disturbances. cannot be determined and the criteria for other ■ Parkinson’s Disease neurocognitive disorders in the DSM-5 cannot Major or mild neurocognitive disorder due be fulfilled. to Parkinson’s disease should be diagnosed in Issues Related to Diagnosis individuals presenting with progressive cogni- in Persons with ID tive deficits with established Parkinson’s dis- Most of what we know about the course of ease and where the symptoms are not better neurocognitive disorders in individuals with explained by another diagnosis. Other features intellectual disability comes from the study of 578 DM-ID-2 Textbook individuals with Down syndrome and probable Krinsky-McHale, Sersen, & Silverman, 2000); Alzheimer’s-type dementia. Individuals with personality and behavior changes and erosion Down syndrome often present with an early on- of social skills are early non-cognitive changes set form of Alzheimer’s-type disease, with clini- (Adams & Oliver, 2010; Ball et al., 2006; Ball, Hol- cal manifestation of dementia in this population land, Treppner, Watson, & Huppert, 2008; Ball, often preceding by more than two decades its Holland, Watson, & Huppert, 2010; Holland, appearance among individuals with non-Down Hon, Huppert, & Stevens, 2000; Oliver, Kalsy, syndrome intellectual disability or the general McQuillan, & Hall, 2011). Physical changes and population (Strydom, Hassiotis, King, & Living- functional skills loss can also appear early in ston, 2009). the course of the condition. Early compromise Development and Course of complex activities of daily living may include Neurocognitive disorders generally have a decline in ability to maintain personal hygiene, progressive and unremitting course (although housekeeping, and work skills; later progres- there are exceptions such as vascular demen- sion involves dyspraxia and decline of basic tia and dementia as a result of head injury) as self-help skills such as toileting, dressing, and opposed to other conditions that may affect eating (Dalton & Fedor, 1998; Evenhuis, 1997). cognition and function such as depression and An increase in maladaptive behaviors may be delirium but which may resolve with timely and evident representing increased impulsivity and targeted treatment. Given that cognitive and personality changes (Kannabiran & Deb, 2010). functional decline occurs as an overlay upon Early personality and behavioral changes and pre-existing deficits associated with develop- cognitive decline associated with frontal lobe mental disability, it is important to consider all degeneration may precede full clinical mani- factors that may complicate both the presen- festation of dementia in individuals with Down tation and the course of the disorder including syndrome (Holland et al., 2000). This initial pre- depression, sensory loss, and other co-morbid sentation is considered to be an important dif- psychiatric or medical illness (McCarron, Gill, ference compared with the general population McCallion, & Begley, 2005, p. 200). (Deb, 2003; (Deb, Hare, & Prior, 2007). Individ- There are few stage-based comparisons of uals are reported to display uncharacteristic the disorder across developmental subtypes. apathy, lack of motivation, and stubbornness. The disorder is often assumed to be more rap- Frontal presentation may also include psychiat- idly progressive among individuals with Down ric symptoms among individuals with no known syndrome than the advancement of dementia previous history of mental illness. The prepon- among those with non-Down syndrome intellec- derance of frontal lobe symptoms reported for tual disability or within the general population, the Down syndrome population, which includes though data on progression is limited (Dodd, neuropsychological findings such as deficits in Bhaumik, & Benbow, 2009). executive function, has led some researchers Early Stage and Late Stage Symptoms to refer to a “frontal-temporal like dementia” of Neurocognitive Disorder in Down (Kannabiran & Deb, 2010). Two types of be- Syndrome havioral problems are manifest in dementia in An IASSID dementia and aging work group Down syndrome: Behavioral excesses such as reviewed the literature published between 1997 irritability, aggression or self-injury, and then and 2008 (Strydom et al., 2009) and described a behavioral deficits that would include slowness, range of early symptoms of Alzheimer’s disease apathy, loss of interest, and lessened social en- in Down syndrome including memory changes, gagement (Oliver et al., 2011) maladaptive behaviors, decreased social en- Late stage symptoms of neurocognitive dis- gagement, and neurological signs. orders in Down syndrome are characterised by Memory and language skills have been not- the individual’s lack of response to the environ- ed to be early cognitive changes (e.g. Devenny, ment, loss of mobility, loss of communication Chapter 25 Neurocognitive Disorders 579 skills, incontinence, seizures and may include neurocognitive disorder. Additional physiologi- Parkinsonian features (Strydom et al., 2009; cal signs may include rigidity, postural abnor- Visser et al., 1997). malities, and pathological grasping and sucking Cognitive Changes reflexes. Memory and other cognitive deficits do some- Neurocognitive Disorder Among times occur in Down syndrome in advance of Individuals with Non-Down Syndrome ID formal clinical diagnosis of neurocognitive We do not know the extent to which descrip- disorder and may be present before the person tions of the development and course of neuro- meets the clinical criteria for dementia (Deven- cognitive disorder based upon Down syndrome ny et al., 2000; Devenny, Zimmerli, Kittler, & are generalizable to adults with intellectual dis- Krinsky-McHale, 2002; Krinsky-McHale, Deven- ability who do not have Down syndrome who ny, & Silverman, 2002). Cognitive decline during manifest cognitive and adaptive skills changes. early and middle stage dementia involves pro- According to the IASSID workgroup, individu- gressively more areas of cognitive functioning, als with non-Down syndrome intellectual disabil- starting with complex cognitive functions, fol- ity and dementia display a general deterioration lowed by visual organization as well as verbal of function and behavioral or emotional changes memory before affecting semantic and short- (Strydom et al., 2009). Further study is required term memory (Devenny et al., 2000). Dyspraxia regarding subtypes of developmental disorder tends to occur at a later stage (Crayton, Oliver, and subtypes of neurocognitive disorder. Holland, Bradbury, & Hall, 1998; Patti, 1999). Generally, the course for those with non-Down Executive functions, visual organization and syndrome intellectual disability of moderate or verbal memory appear to usually decline before more severe disability is similar to those with semantic memory and short-term memory (Kit- Down syndrome, but it has been suggested that tler, Krinsky-McHale, & Devenny, 2006). the course of neurocognitive disorder for indi- Physical Changes viduals with mild intellectual disability is simi- Reduced speech and deterioration in gait lar to the general population (Dodd et al., 2009). may be early symptoms of dementia in Down Memory problems and other changes may be syndrome (V. P. Prasher, 1995). First time adult observed in early stages, and symptoms of de- onset of seizures among individuals with Down pression, lack of energy, low mood, disturbed syndrome with no previous history of epilepsy sleep, persecutory delusions, and auditory hal- may be a marker for neurocognitive disorder lucinations or delusions may also be apparent. (Kannabiran & Deb, 2010). Neurological chang- Observed changes in physical status include uri- es noted among early presenting symptoms nary and fecal incontinence and gait disturbance include late onset myoclonic epilepsy in Down (Cooper, 1997; Cooper & Prasher, 1998). syndrome (LOMEDS); this is characterized by Course of Neurocognitive Disorder myoclonic jerks upon awakening and gener- Although it is known that anatomical brain alized tonic-clonic seizures and generalized changes precede clinical presentation, it is on spikes in waves on EKGs (Möller, Hamer, Oer- the basis of observed behavioral change that tel, & Rosenow, 2001). Incontinence may be neurocognitive disorder is diagnosed. Report- among early physiological signs of neurocogni- ed observed changes that bring individuals to tive change. the attention of practitioners include changes McCarron et al. (2005) have proposed that in daily living skills, work habits, and memory. there is an increased risk of health comorbid- Description of the progression of neurocogni- ities among individuals with Down syndrome tive disorder is complicated by several factors and dementia. Observed medical problems including when during the course of the dis- include respiratory problems, gastrointesti- order individuals receive a formal diagnosis. nal problems, vision, hearing, and weight loss Given the difficulties with early recognition, which may further complicate the course of a an individual may progress to advanced stages 580 DM-ID-2 Textbook of dementia before receiving formal diagnosis. level of intellectual disability, type of develop- Changes in behavior may not be considered as mental disorder, or caregiving factors may in- possible signs of dementia in a population with fluence the course of dementia. pre-existing neurobehavioral problems. Determination of the trajectory of decline Prevalence and Incidence depends upon the point at which significant Major Neurocognitive Disorder change is identified and whether or not change in People With Down Syndrome is effectively tracked over time. Perception of Several of studies have confirmed that de- decline and how decline is manifest depends mentia is frequent in older adults with Down upon such factors as premorbid level of intel- syndrome. Prevalence appears to increase lectual disability and patterns of cognitive abil- sharply in this group between ages 40 and 60. ities, sensory and mood problems as well as en- Prevalence estimates have ranged from 1.4% in vironmental demands placed upon the person those with Down syndrome under 40 (Tyrrell (Aylward, Burt, Thorpe, Lai, & Dalton, 1997; et al., 2001) to 40% in the 50-59 age group (Hol- Strydom et al., 2009). land, Hon, Huppert, Stevens, & Watson, 1998). A variety of factors impede establishing a reli- Coppus and colleagues (2006) found that up able pre-morbid baseline which is needed in order to the age of 60 the prevalence of dementia to track the progression of symptoms. Careful doubled with each 5-year interval (from >49 assessment of baseline functioning would help to 60 years). Studies have varied in their find- in differentiating among delirium, dementia, and ings beyond the age of 60. Some studies have depression and therefore aid in the description of found that prevalence continues to increase, the course of change in cognitive and adaptive with most individuals eventually diagnosed skills. We currently lack the tools to reliably and with dementia (major neurocognitive disor- directly assess individuals on the lower end of der) (Tyrrell et al., 2001; Visser et al., 1997); the range of intellectual functioning. whilst others (Coppus et al., 2006) described a There are insufficient data on the extent to decrease in prevalence to 25.6% at ages 60 and which patient characteristics such as pre-mor- over due to the increased mortality associated bid severity of intellectual ability, pre-morbid with neurocognitive disorder. cognitive and adaptive skills, or co-morbid psy- Incidence increased steadily with increasing chiatric illness may influence trajectory of neu- age, from 2.5 per 100 person years in those aged rocognitive decline (Dodd et al., 2009). Howev- <50 to 13.31 per 100 person years in those aged er, the presence of neurocognitive disorder and 60 and older (Coppus et al., 2006). the severity of intellectual disability are signif- Major Neurocognitive Disorder in People icant predictors of decline in adaptive skills With ID Without Down Syndrome (Deb, Prior, & Bhaumik, 2007). It has also been Estimates of the prevalence and incidence of suggested that the residential setting in which dementia in people with intellectual disabilities care is delivered and other environmental fac- (without Down syndrome) are lower than in the tors may also influence outcomes (Courtenay, Down syndrome population but may be higher Jokinen, & Strydom, 2010). than the general population average. More research is needed with regards to Cooper (1997) found a prevalence rate of the natural history of cognition and adaptive 20% in people aged 65 years and over. Later skills in aging adults with intellectual disabil- Strydom and colleagues (2007) found a similar ity across levels of intellectual impairment prevalence rate of 18.3% among those aged 65 and types of developmental disorder to allow and older. Alzheimer’s disease was found to be for clearer distinction between normative and the most common type of dementia and had non-normative changes in function as individ- a prevalence of 12%, three times greater than uals age. Further research is required to deter- comparable general older adult population mine the extent to which subtype of dementia, rates. One study has, however, found demen- Chapter 25 Neurocognitive Disorders 581 tia rates comparable to the general population Application of Diagnostic Criteria in the over 65 age group (Zigman et al., 2004) to People with ID though this group later reanalyzed their data General Considerations due to diagnostic issues and adjusted their es- Due to generally better access to medical and timate to a slightly higher rate (Zigman, 2013). social care and healthier lifestyles, people with This group also found an incidence rate for intellectual disability are living longer and there- Alzheimer’s disease to be 8 cases over 3 years fore increasingly at risk of age-related disorders in a cohort of approximately 100 participants such as neurocognitive disorders. Although neu- over the age of 65. Strydom, Chan, King, Has- rocognitive disorders are more common in this siotis, & Livingston (2013) found an overall population, a number of factors make diagnosis incidence rate for those aged 60 of 54.6/1000 of neurocognitive disorders in adults with intel- person years with the highest incidence rate lectual disability difficult (for reviews see (Evans in the age group 70–74 years. et al., 2013; Moran, Rafii, Keller, Singh, & Janicki, Differential Diagnosis and Comorbidity 2013; Strydom et al., 2010). Any condition that affects cognitive func- The main difficulties include that 1) baseline tioning should be considered in the differential functioning varies widely between individuals, diagnosis of a neurocognitive disorder – the making it difficult to interpret change and to possibilities to consider has been reviewed else- apply screening approaches across the popu- where (Knopman et al., 2001). It is particularly lation; 2) individuals with intellectual disabil- important to exclude common comorbidities ity may be unable to answer questions about in intellectual disability such as hearing or vi- their memory or higher cognitive functioning; sion loss, thyroid function disorders (particular 3) there are many other treatable conditions in individuals with Down syndrome; (Määttä, that could explain an apparent decline in cog- Kaski, Taanila, Keinänen-Kiukaanniemi, & Iiva- nitive and functional abilities, including med- nainen, 2006; Määttä et al., 2011), and mental ical co-morbidities, mental health problems, health concerns such as depression – see the and behavioral responses to stress or change in section below on general considerations for environment, and 4) in many geographic areas, more detail. there is a relative paucity of qualified health- care providers for this population relative to Functional Consequences the general population (Moran et al., 2013). The Overall, the natural history of the disorder diagnosis of dementia in people with intellectu- involves a progressive loss of skills, increased al disability is further hampered by the lack of loss of independence and increased dependence reliable and standardized diagnostic tools and upon others for personal assistance and main- procedures, especially in the early stages of tenance of daily routine. Later stages of demen- decline. Furthermore, the use of investigations tia among individuals with Down syndrome are such as neuroimaging and lumbar puncture is associated with dyspraxia and extensive loss limited by its acceptability in this population, as of self-help skills (Prasher, 1995), as well as the well as the complexities of interpreting results. development of neurological symptoms such as As previously discussed, the presentation of problems with swallowing, myoclonic jerks and major neurocognitive disorders may differ in seizures. people with intellectual disability compared Neurocognitive decline and its functional im- to the general population. Memory loss may plications impact upon caregiving and health not be prominent in the early stages. Cognitive care practices including the level of supervi- changes are frequently present, but they may be sion at which an individual needs to stay safe, difficult to evaluate because of limitations in staffing to provide personal assistance, and the individual’s language, communication, and planning including allocation of resources and functional abilities. In contrast to the general environmental modifications. population, people with intellectual disability 582 DM-ID-2 Textbook may experience a predominance of changes in ABDQ ; (Prasher, Farooq, & Holder, 2004) ), functioning (i.e. activities of daily living and several cognitive functioning test batteries work habits) early in the course (Aylward et al., completed with the person (e.g. Burt-Aylward 1997; Strydom et al., 2010). Functional abilities battery [Burt & Aylward, 2000]; NAID [Crayton can be influenced by many different factors and et al., 1998]), and proxy ratings of adaptive abil- are more dependent on disability level and co- ity or everyday functioning (e.g. Vineland Adap- morbidity than dementia (Lin et al., 2014). Be- tive behavior scale, (Sparrow, 2011) or dementia havioral problems, such as behavioral excesses symptoms (e.g. CAMDEX-DS informant inter- (e.g. restlessness, aggression) or deficits (e.g. view, ( Ball et al., 2004). Although proxy report withdrawal, inactivity), may also be an early has limitations, this remains the most feasible sign associated with neurocognitive disorders option to track change over time from all indi- (Adams et al., 2008, p. 200; Oliver et al., 2011). viduals with intellectual disabilities regardless Neurological symptoms associated with de- of their ability. mentia such as epileptic seizures and depth per- Ultimately diagnosis of a neurocognitive dis- ception difficulties may occur more often than order requires the exclusion of other conditions in the general population, particularly in those that may be implicated in either apparent or ac- with Down syndrome ( Lott & Dierssen, 2010; tual cognitive or functional decline. A compre- McCarron, McCallion, Reilly, & Mulryan, 2014). hensive medical history (Moran et al., 2013) and Sensory deficits (particularly hearing loss) are a physical work-up should therefore be conduct- also associated with cognitive decline or de- ed as part of any assessment (Dodd et al., 2009). mentia in Down syndrome (Lott & Dierssen, The impact of sensory losses such as impaired 2010; McCarron et al., 2014). Therefore, the as- sight and hearing should be considered (Have- sessment and identification of dementia should man et al., 2010; Haveman et al., 2011). People take into account a nuanced consideration of with Down syndrome often experience the ef- functional abilities, cognitive status, behavioral fects of premature aging including cataracts indicators, and clinical factors. (Evenhuis, 1997; Evenhuis, Theunissen, Denk- There is no universal test for dementia that ers, Verschuure, & Kemme, 2001) and presbya- can be used for older people with intellectu- cusis (Haveman et al., 2010), which can impact al disability who are showing deterioration in on function. function, though an assessment of cognitive A recent Finnish population-based study of function is recommended (Moran et al., 2013). case records of older people with Down syn- Furthermore, the standard tests used on the drome also found that thyroid disease was com- general population are inappropriate for people mon (Määttä et al., 2006; Määttä et al., 2011), with intellectual disability and different types which should be excluded as the cause of cog- of assessment tools are required for those with nitive decline. Seizures may also be common in mild intellectual disability compared to those this population, but it needs to be established with more severe intellectual disability. The op- whether this preceded the onset of decline, as tions for formal assessment in this population seizures often develop with Alzheimer’s-type have been reviewed elsewhere (Zeilinger, Stie- dementia in individuals with Down syndrome hl, & Weber, 2013) and include proxy-rated (i.e. and affect the progression of the disorder (Lott caregiver-rated) dementia screening question- et al., 2012). naires (e.g. Dementia Questionnaire for people Other physical causes of cognitive decline with Mental Retardation or Learning disabili- including vitamin deficiencies, electrolyte im- ties - also referred to as DMR or DLD; (Even- balances, chronic diseases including central huis, 1997); Dementia Screening Questionnaire nervous system manifestations of untreated for Individuals with Intellectual disabilities, coeliac disease, occult malignancies, and cen- DSQIID ( Deb, Hare, Prior, & Bhaumik, 2007, tral nervous system conditions such as tumors, p. 200); The Adaptive Behavior Questionnare, inflammatory conditions, hydrocephalus, and Chapter 25 Neurocognitive Disorders 583 infections such as neuro-syphilis should be ex- declines in excess of “normal aging,” which cluded. Mental health conditions such as depres- may be viewed as a prodromal stage of de- sion are common in older individuals with intel- mentia, particularly in older adults with Down lectual disability regardless of etiology of the syndrome. Using this type of approach, sev- intellectual disability (Cooper, Smiley, Morrison, eral groups found that the prodromal signs of Williamson, & Allan, 2007) and affect functional Alzheimer’s disease in older adults with Down and cognitive abilities in people with intellectual syndrome often included signs of frontal lobe disability (Hermans & Evenhuis, 2013). A psy- dysfunction such as emotional changes, behav- chiatric and life events examination is therefore ioral problems and frontal release signs (Ball et also recommended as part of a comprehensive al., 2006; NelsonOrme, Osann, & Lott, 2001; Urv, work-up for neurocognitive disorders. Zigman, & Silverman, 2010; Urv, Zigman, Silver- Methodology man, & MacLean, 2008). We undertook a comprehensive literature In adults with intellectual disability without search across several databases (EMBASE, Down syndrome, informants tended to report Medline, Cinahl) using all equivalent terms general deterioration of functioning more than for intellectual disability (e.g. mental retarda- memory or other cognitive changes (Strydom et tion and learning disabilities) and combining al., 2007). However, in individuals who can com- these with terms for neurocognitive disorders plete cognitive testing, change in cognitive func- (dementia, Alzheimer’s disease). Additionally, tioning (particularly episodic memory) has been we completed searches using terms for other observed in adults with Down syndrome sever- types of neurocognitive disorders, including al years before clinical diagnosis of dementia fronto-temporal dementia, Lewy body demen- (Crayton et al., 1998; Devenny et al., 2002; Krin- tia, and vascular dementia. We also completed sky-McHale et al., 2002). Nevertheless, changes searches for delirium and mild neurocognitive in behavior and personality now form the basis disorder and equivalent terms (e.g. mild cogni- of several caregiver-reported screening tools for tive impairment). dementia, particularly for individuals with Down Searches were limited to English and the time syndrome (Oliver et al., 2011; Deb et al., 2007; frame 2008-February 2014 because a compre- Whitwham, McBrien, & Broom, 2011). hensive series of reviews included the literature Strydom, Chan, Fenton, et al. (2013) defined prior to that date (Haveman et al., 2010; Stry- mild cognitive impairment as individuals who dom et al., 2010; Torr, Strydom, Patti, & Jokinen, had previously screened positive for possible 2010), and we also consulted the reference lists dementia on the Dementia Questionnaire for of these reviews. People with Intellectual Disability screening Review of Research Applying tool (DMR; Evenhuis, 1992), or because of con- to People with ID cerns about decline in functioning or memory, No research studies were identified concerning and explored its predictive value for dementia the application or modification of criteria for de- diagnoses two years later using ICD-10 and lirium in individuals with intellectual disability. DSM-IV criteria. Only 13% of those with mild A small number of studies have considered cognitive impairment were diagnosed with the diagnostic issues related to mild neurocog- dementia after follow-up of approximately 2.9 nitive disorder (similar to but not exactly the years, which was not much different than that same as mild cognitive impairment) and associ- of a “normal” state. This compares to an annual ated symptoms in individuals with intellectual dementia conversion rate of 5-10% for mild cog- disability. While there is generally an emphasis nitive impairment reported in the general popu- on earlier detection of underlying disease, this lation (Petersen, 2011). presents challenges in individuals with intellec- Silverman, Zigman, Krinsky-McHale, Ryan, tual disability. One approach has been to iden- and Schupf (2013) defined mild cognitive im- tify adults with intellectual disability who show pairment as those showing cognitive decline 584 DM-ID-2 Textbook larger than expected with aging but having in- disability (Bell, Turnbull, & Bruce Kidd, 2009), sufficient“ breadth or severity” to be considered or sensory impairments (Moran et al., 2013), dementia and applied this to their study of de- and difficulties in interpreting periods of pla- mentia in older adults with intellectual disabili- teau in vascular dementia and the floor effect in ty without Down syndrome. Although they iden- advanced dementia when longitudinal informa- tified dementia or mild cognitive impairment in tion is not available. more than 20% of their sample, they had diffi- DSM-5 criteria for major neurocognitive culty designating the majority of these with cer- disorder could improve the ability to diag- tainty to a specific category. In their review of nose dementia in individuals with intellectual the literature on mild cognitive impairment in disabilities. The hierarchical approach to sub- intellectual disability, Krinsky-McHale & Silver- typing (i.e. requiring that criteria for major or man (2013) emphasized the need for empirically mild neurocognitive disorder are met before based assessment methods and classification applying criteria for neurocognitive disorder criteria for mild cognitive impairment. subtypes such as Alzheimer’s disease, fronto- Several studies were identified which applied temporal lobar degeneration, vascular disease, ICD-10 and DSM-IV dementia criteria for major and Lewy body disease) could be helpful. The neurocognitive disorder (dementia) in individ- de-emphasis of a central focus on memory uals with intellectual disability. Clinical judg- deficits DSM-IV( ) in favor of the broader inclu- ment, based on ICD-10 criteria, resulted in more sion of six possible cognitive domains, as well adults with Down syndrome diagnosed with emphasis on “decline” from a previous level of dementia than methods based on test batter- performance (criterion A) rather than “impair- ies (Diana B. Burt et al., 2005). DSM IV criteria ment,” are important changes. Coupled with the showed substantial inter-rater reliability (Kap- option for cognitive decline to be reported by pa = 0.68) (Strydom, Chan, Fenton, et al., 2013) the individual, a knowledgeable informant, or and were found to diagnose more people with a clinician (A1), these changes should improve dementia than ICD-10 criteria (A. Strydom et al., predictive validity of the criteria. 2007). However, diagnostic instability may be However, some aspects of the criteria may more common in individuals with intellectual prove difficult in their application to people disability compared to the general population, with an intellectual disability, particularly affecting the predictive validity of diagnoses. those with more severe disabilities or those DSM-IV criteria diagnosed a few false positive with communication difficulties. Firstly, it is cases with dementia because of the extent of important to distinguish neurocognitive dis- pre-existing cognitive deficits, but cases were order from premorbid cognitive impairment or occasionally missed when caregivers did not impairments due to non-degenerative or stable report memory loss in those who did not have conditions such as brain injury. Secondly, the sequential cognitive test data. Sensitivity and requirement that evidence of cognitive decline specificity for either dying or being re-diag- be documented by standardized neuropsy- nosed with dementia after approximately 2.9 chiatric testing or another quantified clinical years after a DSM-IV diagnosis of dementia assessment (A2) is particularly difficult in the was 0.28 and 0.95, respectively (Andre Strydom, context of intellectual disability. For people Chan, Fenton, et al., 2013). in whom standardized neuropsychological as- The challenges in diagnosing dementia in this sessment or other quantified assessment is not population included variable quality of infor- feasible, it is suggested that caregiver ratings mant reports with poor judging of indicators of cognitive functioning should be sufficient of early and intermediary dementia (Herron & to meet this criterion (level of evidence: IV). Priest, 2013), difficulties in the assessment of A limitation of this approach is that some peo- those with moderate and severe intellectual ple with intellectual disability may already be Chapter 25 Neurocognitive Disorders 585 performing at the floor of such instruments. we suggest that this diagnostic category should Furthermore, criterion B suggests that the be used with caution in individuals with intel- cognitive deficits should be severe enough to lectual disabilities, and further research to help interfere with independence in daily activi- identify biomarkers and neurocognitive tests that ties – however, individuals with intellectual improve the predictive validity of mild neurocog- disability will by definition already have lim- nitive diagnosis will be useful. itations in functioning, and it should therefore Evaluating the Level of Evidence be clarified that a significant change from There is limited evidence on the use of diag- pre-existing ability in everyday functioning is nostic criteria for dementia (major neurocogni- required (Moran et al., 2013). tive disorder) in this population and extremely The diagnostic criteria for mild neurocogni- limited evidence for the use of criteria for mild tive disorder requires modest cognitive decline cognitive impairment and mild neurocognitive from previous level of function in at least one of disorder. six possible cognitive domains. The presence of cognitive decline is determined by a combina- Adults with ID tion of the concern of an individual, informant Most of the existing studies on dementia cri- or clinician, together with modest impairment teria in individuals with intellectual disability in performance in comparison to prior or ex- have been with adults with mild to moderate pected results or clinical assessment. There is intellectual disability. Jamieson-Craig, Scior, a specific requirement that cognitive deficits do Chan, Fenton, & Strydom (2010) examined ret- not result in additional supports being required rospective caregiver reports of early symptoms by the individual. of dementia in adults with intellectual disabili- The existing literature in people with intellec- ty and found that reports of change in memory tual disability highlights the difficulty in identi- were a better indicator for possible dementia in fying cognitive deficits of such fine granularity those with mild intellectual disability, while in from pre-existing cognitive deficits, and high- those with more severe intellectual disability lights the poor predictive validity of mild cogni- decline in everyday functioning was a more re- tive impairment definitions in people with intel- liable indicator of possible dementia. In gener- lectual disability. There may be several reasons al, caution is advised when applying dementia for changes in cognitive function in individuals criteria in people with more severe intellectual with intellectual disability who may be particu- disability. larly sensitive to the cognitive effects of physi- Children and Adolescents with ID cal illness, environmental disturbance, changes We have not found any studies that have ap- in support, or mental illness and stress. These plied diagnostic criteria for delirium or demen- factors need to be considered in addition to tia in children and adolescents with intellectual the possibility of mild neurocognitive disorder. disability. However, most clinicians working with older in- dividuals with Down syndrome will recognize Summary of Limitations in Applying the value in being able to apply a diagnosis of DSM-5 Criteria to People with ID mild neurocognitive disorder when symptoms Several limitations in applying the criteria for of Alzheimer’s disease are recognized early, i.e. neurocognitive disorders in individuals with in- before it has a significant impact on the person’s tellectual disability are apparent: level of functioning. On the flipside, there is a 1. Difficulty in objectively defining cognitive risk of overdiagnosis, and there is not sufficient impairment and decline in a population with evidence that people with this diagnosis will pre-morbid deficits (very difficult when cog- progress to major neurocognitive disorder. nitive deficits are more subtle). This is the In the absence of evidence for the DSM-5 diag- main concern with applying the criteria for nostic criteria of mild neurocognitive disorders, mild neurocognitive disorder, which does not 586 DM-ID-2 Textbook

require functional decline to be present and Etiology and Pathogenesis could thus result in over-diagnosis in this pop- Biological Factors for Delirium ulation. However, this label may be useful to Delirium is always caused by an underlying identify individuals at high risk for future de- medical condition or combination of conditions cline, particularly in research settings, as long but may be exacerbated in the context of func- as it is not prematurely concluded that all per- tional impairment, immobility, a history of falls, sons with more subtle cognitive decline will low levels of activity, and use of illicit drugs progress to full-blown dementia. and medications with psychoactive properties 2. Formal neuropsychological testing: (particularly alcohol and anticholinergic drugs) (American Psychiatric Association, 2013). a. People with intellectual disability con- trast with the general population where Genetic Factors for Major and Mild Neurocognitive Disorders clinicians may have greater control The amyloid cascade hypothesis remains the over factors which “optimize” cognitive most prominent etiological theory for Alzheim- test performance, whereas clinicians er’s disease and is of much interest in Down working with this population have to syndrome, as the APP gene on chromosome deal with considerable unpredictabil- 21 is strongly implicated in the development of ity (factors include contextual issues, Alzheimer’s neuropathology in these patients. Re- emotional states, sensory problems, cent advances in Positron Emission Tomography medical status, medications etc.). (PET) imaging using new ligands have enabled b. Limited range of tests suitable for this researchers to show deposition of cerebral amy- population, especially for those with loid and tau in people with Down syndrome (Nel- more severe intellectual disability. son et al., 2005) supporting the role of these pro- teins in the development of Alzheimer’s disease c. Individuals may have a wide range of in Down syndrome. ApoE4 is a strong risk factor baseline abilities across different do- for Alzheimer’s disease in the general population, mains, and there is considerable be- and also relevant in Down syndrome (Prash- tween-individual variation. er, Chowdhury, Rowe, & Bain, 1997). Oxidative 3. Questionnaire-based assessment of cogni- stress is also thought to play a role in the patho- tive functioning completed with or by care- physiology of Alzheimer’s disease and is particu- givers. larly of interest in Down syndrome, as the dosage sensitive superoxide dismutase gene (SOD1) is lo- a. Questions often do not map well onto cated on chromosome 21. However, a randomized specific cognitive domains. controlled trial of antioxidant supplementation in b. The “context” is not considered, e.g. people with Down syndrome and dementia had whether a task is regularly ignored be- disappointing results (Lott et al., 2011). Neverthe- cause the person is unwilling to do it less, understanding the link between Down syn- rather than unable to do it, or the famil- drome and Alzheimer’s disease would contribute iarity of the person with his/her care- substantially to our understanding of the disease givers. in general. Little attention has been paid to the risk of 4. Questionnaires do not discriminate between dementia in other specific intellectual disabil- “physical” and “cognitive” reasons for func- ity syndromes. Several intellectual disability tional impairments. syndromes have neurocognitive decline as a 5. Reliability of informant reports of impair- common characteristic — these include Cock- ment or decline is also occasionally an issue, ayne syndrome, Rett syndrome, and Sanfilippo particularly when information is obtained syndrome. Cockayne syndrome (progeria-like from different caregivers at different times. syndrome), a rare autosomal recessive dis- Chapter 25 Neurocognitive Disorders 587 order, is characterized by premature aging, ple with Down syndrome. Other factors such as including neurodegeneration and dementia the raised mean corpuscular volume (MCV) of (Rapin et al., 2006). Sanfilippo syndrome, or mu- red blood cells (RBC) (Prasher, Uppal, Parveen, copolysaccharidosis III, is a lysosomal storage Adams, & Haque, 2013), impaired balance be- disease caused by the impaired degradation of tween excitatory and inhibitory neurotransmit- heparan sulfate and characterized by severe ter system, particularly involving GABAA sys- central nervous system degeneration. There tem (Rissman & Mobley, 2011), and higher levels are several types, depending on the genetic or- of macrophage inflammatory protein-1 (MIP-1) igin of the disease. Although most people with (Carta et al. cited in Kannabiran & Deb, 2010) the disease die during childhood, those with have been implicated as risk factors but further type B disease (i.e. affecting alpha-N-acetylglu- proof is required to confirm these findings. cosaminidase) may survive into adulthood. A Use of certain medications particularly those very high proportion of adults with Sanfilippo with anticholinergic properties may enhance the syndrome type B developed dementia (Moog expression of neurocognitive disorder. A number et al., 2007; Skandar, Schoonbrood-Lenssen, Van of medication classes have been reported to be den Akker, & Maaskant, 2005). associated with possible worsening of cognitive There are controversial findings in the litera- function in people with dementia. These include ture regarding whether or not severity of intel- antihistamines, especially first generation (di- lectual disability acts as a risk factor for demen- phenhydramine, hydroxyzine, promethazine), tia (see review by Evans et al., 2013). bladder agents (oxybutynin, tolterodine), certain Traumatic brain injury may increase the risk pain medications (meperidine, propoxiphene), of major or mild neurocognitive disorder due to tricyclic antidepressants, certain antipsychotics Alzheimer’s disease in the general population (chlorpromazine, clozapine, pimozide) ,and ben- (Fleminger, Oliver, Lovestone, Rabe-Hesketh, & zodiazepines (see review by Moran et al., 2013). Giora, 2003). Age is the strongest risk factor for Psychosocial Factors Alzheimer’s disease, and in the case of people Esbensen, Mailick, & Silverman (2013) found with Down syndrome the effect of age is inde- that higher initial maternal and paternal levels pendent of severity of intellectual disabilities of depressive symptoms and lower initial levels and gender (Strydom et al., 2009). Multiple vas- of paternal relationship quality were significant cular risk factors influence risk for Alzheimer’s predictors of a higher likelihood of a dementia disease and may act by increasing cerebrovas- diagnosis in the adults with Down syndrome ten cular pathology or also through direct effect on years later. Furthermore, lower initial levels of Alzheimer’s disease pathology (see review by maternal positive psychological well-being pre- Deb & McHugh, 2010). A positive family histo- dicted a higher likelihood of developing demen- ry of Alzheimer’s disease and inactive lifestyle tia in adults with Down syndrome ten years later, may also act as risk factors ( Deb, 2003). but the effect was only marginally significant. Coppus et al. (2012) showed that in individuals Poorer overall physical health and depression with Down syndrome, higher levels of plasma were shown to be associated with an increased Aβ40 and Aβ42 were associated with increased rate of dementia in people with intellectual dis- risk of dementia. Others have failed to show ability (Evenhuis, 1997). However, it is not clear this association with dementia but showed Aβ40 to what extent other known risk factors for de- level to be associated with cognitive decline mentia in the non- intellectual disability general in people with Down syndrome (Head et al., population such as lack of engagement in men- 2011). On the other hand (Matsuoka et al., 2009) tally stimulating leisure and social activities, showed that the ratio of Aβ42 to Aβ40 rather than poor educational achievement, emotional trau- absolute levels of the peptides is important to ma and associated post-traumatic stress disor- the pathophysiology of Alzheimer’s disease in der, poor diet, and lack of exercise also have a genetically vulnerable population such as peo- role in individuals with intellectual disability. 588 DM-ID-2 Textbook

Neurocognitive Disorders Delirium DSM-5 Diagnostic Criteria Applying Criteria for Mild-Profound ID A. A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift A. Needs to be interpreted as a change attention) and awareness (reduced orientation to the environment). from baseline levels of attention and awareness B. The disturbance develops over a short period of time (usually hours to a few days), B. No change represents a change from baseline attention and awareness, and tends to fluctuate during the course of the day. C. An additional disturbance in cognition (e.g., memory deficit, disorientation, lan- C. Needs to be interpreted as a change guage, visuospatial ability, or perception). from baseline cognitive ability

D. These cognitive disturbances are not better explained by another preexisting, es- D. No change tablished, or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma. E. There is evidence from the history, physical examination, or laboratory findings that E. No change the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e., due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple etiologies. Substance intoxication delirium: This diagnosis should be made instead of substance No change intoxication when the symptoms in criteria A and C predominate in the clinical picture and they are sufficiently severe to warrant clinical attention. Substance withdrawal delirium: This diagnosis should be made instead of substance No change withdrawal when the symptoms in criteria A and C predominate in the clinical picture and they are sufficiently severe to warrant clinical attention. Other specified delirium: as for delirium but symptoms do not meet the full criteria but No change cause clinically significant distress or impairment. NOTE: The clinician must specify the reason the delirium does not meet the full criteria. Unspecified delirium: as for delirium but symptoms do not meet the full criteria but cause No change clinically significant distress or impairment. NOTE: The clinician does not specify the reason the delirium does not meet the full criteria.

Major Neurocognitive Disorder DSM-5 Diagnostic Criteria Applying Criteria for Mild-Profound ID A. Evidence of significant cognitive decline from a previous level of performance in A. Take care to determine previous level one or more cognitive domains (complex attention, executive function, learning and of performance and change in perfor- memory, language, perceptual-motor, or social cognition) based on: mance need to be clearly established 1. Concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function; and 2. A substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing or, in its absence, another quantified clinical assessment. Neuropsychological tools should have been designed for individuals with an intellectual disability and/or validated in this population; including proxy-rated tools of cognitive performance B. The cognitive deficits interfere with independence in everyday activities (i.e., at a B. Needs to be a change from previous minimum, requiring assistance with complex instrumental activities of daily living level of functioning (i.e. measured such as paying bills or managing medications). against the person’s own premorbid baseline) C. The cognitive deficits do not occur exclusively in the context of a delirium. C. No change D. The cognitive deficits are not better explained by another mental disorder (e.g., major D. No change depressive disorder, schizophrenia). Chapter 25 Neurocognitive Disorders 589

Mild Neurocognitive Disorder DSM-5 mild neurocognitive disorder has the same criteria as for major neurocognitive disorder, except that the cognitive decline is modest/mild and does not interfere with capacity for indepen- dence in everyday activities. The reliability and validity of this diagnosis in individuals with ID has not been established and we advise caution in using this diagnosis.

Major or Mild Neurocognitive Disorder Due to Alzheimer’s Disease DSM-5 Diagnostic Criteria Applying Criteria for Mild-Profound ID A. The criteria are met for major or mild neurocognitive disorder A. No change, but see concerns about mild neurocognitive change B. There is insidious onset and gradual progression of impairment B. No change, but see comments above about change from previ- in one or more cognitive domains (for major neurocognitive ous level of performance disorder, at least two domains must be impaired). C. Criteria are met for either probable or possible Alzheimer’s C. No change disease as follows: For major neurocognitive disorder: Probable Alzheimer’s disease is diagnosed if either of the following is present; otherwise, possible Alzheimer’s dis- ease should be diagnosed: 1. Evidence of a causative Alzheimer’s disease genetic muta- tion from family history or genetic testing. 2. All three of the following are present: a. Clear evidence of decline in memory and learning and at least one other cognitive domain (based on detailed history or serial neuropsychological testing). b. Steadily progressive, gradual decline in cognition, without extended plateaus. c. No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological, mental, or systemic disease or condition likely contributing to cognitive decline). For mild neurocognitive disorder: Probable Alzheimer’s disease is diagnosed if there is evi- dence of a causative Alzheimer’s disease genetic mutation from either genetic testing or family history. Possible Alzheimer’s disease is diagnosed if there is no ev- idence of a causative Alzheimer’s disease genetic mutation from either genetic testing or family history, and all three of the following are present:

1. Clear evidence of decline in memory and learning. 2. Steady progressive, gradual decline in cognition, without extended plateaus. 3. No evidence of mixed etiology (i.e., absence of other neu- rodegenerative or cerebrovascular disease, or another neurological or systemic disease or condition likely con- tributing to cognitive decline). D. The disturbance is not better explained by cerebrovascular dis- D. No change ease, another neurodegenerative disease, the effects of a sub- stance, or another mental, neurological, or systemic disorder.

Major or Mild Frontotemporal Neurocognitive Disorder No change from DSM-5 criteria, but see concerns about mild neurocognitive change. 590 DM-ID-2 Textbook

Major or Mild Neurocognitive Disorder with Lewy Bodies DSM-5 Diagnostic Criteria Applying Criteria for Mild-Profound ID

A. The criteria are met for major or mild neurocognitive disorder. A. No change, but see concerns about mild neurocognitive change

B. The disorder has an insidious and gradual progression B. No Change

C. The disorder meets a combination of core diagnostic features and sug- C. No Change gestive diagnostic features for either probable or possible neurocog- nitive disorder with Lewy bodies. For probable major or mild neurocog- nitive disorder with Lewy bodies, the individual has two core features, or one suggestive feature with one or more core features. For possible major or mild neurocognitive disorder with Lewy bodies, the individual has only one core feature, or one or more suggestive features. 1. Core diagnostic features: a. Fluctuating cognition with pronounced variations in attention and alertness. b. Recurrent visual hallucinations that are well-formed and detailed. c. Spontaneous features of Parkinsonism, with onset subsequent to the development of cognitive decline 2. Suggestive diagnostic features: a. Meets criteria for rapid eye movement sleep behavior disorder b. Severe neuroleptic sensitivity D. The disturbance is not better explained by cerebrovascular disease, D. No Change another neurodegenerative disease, the effects of a substance, or an- other mental, neurological, or systemic disorder.

Major or Mild Vascular Neurocognitive Disorder DSM-5 Diagnostic Criteria Applying Criteria for Mild-Profound ID A. The criteria are met for major or mild neurocognitive disorder A. No change, but see concerns about mild neurocogni- tive change B. The clinical features are consistent with a vascular etiology, as sug- B. No Change gested by either of the following: 1. Onset of the cognitive deficits is temporally related to one or more cerebrovascular events. 2. Evidence for decline is prominent in complex attention (including processing speed) and fronto-executive function. C. There is evidence of the presence of cerebrovascular disease from his- C. No Change tory, physical examination, and/or neuroimaging considered sufficient to account for the neurocognitive deficits. D. The symptoms are not better explained by another brain disease or D. No Change systemic disorder. Chapter 25 Neurocognitive Disorders 591

Major or Mild Vascular Neurocognitive Disorder (continue) DSM-5 Diagnostic Criteria Applying Criteria for Mild-Profound ID Probable vascular neurocognitive disorder is diagnosed if one of the following is present; otherwise possible vascular neurocognitive disorder should be diagnosed: 1. Clinical criteria are supported by neuroimaging evidence of sig- nificant parenchymal injury attributed to cerebrovascular disease (neuroimaging-supported). 2. The neurocognitive syndrome is temporally related to one or more documented cerebrovascular events. 3. Both clinical and genetic (e.g., cerebral autosomal dominant arteri- opathy with subcortical infarcts and leukoencephalopathy) evidence of cerebrovascular disease is present. Possible vascular neurocognitive disorder is diagnosed if the clinical criteria are met but neuroimaging is not available and the temporal rela- tionship of the neurocognitive syndrome with one or more cerebrovascular events is not established.

Major or Mild Neurocognitive Disorder Due to Traumatic Brain Injury DSM-5 Diagnostic Criteria Applying Criteria for Mild-Profound ID A. The criteria are met for major or mild neurocognitive disorder A. No change, but see concerns about mild neurocogni- tive change B. There is evidence of a traumatic brain injury – that is, an impact to B. No Change the head or other mechanisms of rapid movement or displacement of the brain within the skull, with one or more of the following: 1. Loss of consciousness 2. Posttraumatic amnesia 3. Disorientation and confusion 4. Neurological signs (e.g. neuroimaging demonstrating injury; a new onset of seizures; a marked worsening of a pre-existing seizure disorder; visual field cuts; anosmia; hemiparesis C. The neurocognitive disorder presents immediately after the occurrence C. No Change of the traumatic brain injury or immediately after recovery of conscious- ness and persists past the acute post-injury period.

Substance-/Medication-induced Major or Mild Neurocognitive Disorder DSM-5 criteria for substance-medication-induced neurocognitive disorder are the same as for other mental disorders, without adaptation, with the additional need for presence of the criteria for major or mild neurocognitive disorder. Major or Mild Neurocognitive Disorder Due to HIV Infection Major or Mild Neurocognitive Disorder Due to Prion Disease Major or Mild Neurocognitive Disorder Due to Parkinson’s Disease Major or Mild Neurocognitive Disorder Due to Huntington’s Disease Major or Mild Neurocognitive Disorder Due to Another Medical Condition Major or Mild Neurocognitive Disorder Due to Multiple Etiologies 592 DM-ID-2 Textbook

Unspecified Neurocognitive Disorder DSM-5 also provides criteria for major and mild neurocognitive disorders due to HIV, prion dis- ease, Parkinson’s disease, Huntington’s disease, or multiple etiologies. No modifications are sug- gested to these criteria. There is also a category for unspecified neurocognitive disorder.

References ity Research, 48(6), 611–620. doi:10.1111/ Adams, D., & Oliver, C. (2010). The relationship j.1365-2788.2004.00630.x between acquired impairments of executive Ball, S. L., Holland, A. J., Treppner, P., Watson, function and behaviour change in adults P. C., & Huppert, F. A. (2008). Executive with Down syndrome. Journal of Intellec- dysfunction and its association with per- tual Disability Research, 54(5), 393–405. sonality and behaviour changes in the de- doi:10.1111/j.1365-2788.2010.01271.x velopment of Alzheimer’s disease in adults Adams, D., Oliver, C., Kalsy, S., Peters, S., Bro- with Down syndrome and mild to moderate quard, M., Basra, T. … McQuillan, S. (2008). learning disabilities. The British Jour- Behavioural characteristics associated nal of Clinical Psychology, 47(Pt 1), 1–29. with dementia assessment referrals in doi:10.1348/014466507X230967 adults with Down syndrome. Journal of In- Ball, S. L., Holland, A. J., Watson, P. C., & Hup- tellectual Disability Research, 52(4), 358– pert, F. A. (2010). Theoretical exploration 368. doi:10.1111/j.1365-2788.2007.01036.x of the neural bases of behavioural disin- American Psychiatric Association. (2013). Di- hibition, apathy and executive dysfunc- agnostic and statistical manual of men- tion in preclinical Alzheimer’s disease in tal disorders (5th ed.). Washington, D.C: people with Down’s syndrome: potential American Psychiatric Publishing. involvement of multiple frontal-subcorti- American Psychiatric Association. (2006). Amer- cal neuronal circuits. Journal of Intellec- ican Psychiatric Association practice tual Disability Research, 54(4), 320–336. guidelines for the treatment of psychiatric doi:10.1111/j.1365-2788.2010.01261.x disorders: Compendium 2006. Washington, Bell, D. M., Turnbull, A., & Bruce Kidd, W. DC: American Psychiatric Pubishing. (2009). Differential diagnosis of dementia Aylward, E. H., Burt, D. B., Thorpe, L. U., Lai, F., in the field of learning disabilities: A case & Dalton, A. (1997). Diagnosis of dementia study. British Journal of Learning Dis- in individuals with intellectual disability. abilities, 37(1), 56–65. doi:10.1111/j.1468- Journal of Intellectual Disability Research, 3156.2008.00524.x 41(2), 152–164. doi:10.1111/j.1365-2788.1997. Burt, D. B., & Aylward, E. H. (2000). Test battery tb00692.x for the diagnosis of dementia in individuals Ball, S. L., Holland, A. J., Hon, J., Huppert, F. A., with intellectual disability. Working group Treppner, P., & Watson, P. C. (2006). Person- for the establishment of criteria for the di- ality and behaviour changes mark the early agnosis of dementia in individuals with in- stages of Alzheimer’s disease in adults with tellectual disability. Journal of Intellectual Down’s syndrome: findings from a prospec- Disability Research, 44 ( Pt 2), 175–180. tive population-based study. International Burt, D. B., Primeaux-Hart, S., Loveland, K. A., Journal of Geriatric Psychiatry, 21(7), Cleveland, L. A., Lewis, K. R., Lesser, J., & 661–673. doi:10.1002/gps.1545 Pearson, P. L. (2005). Tests and medical Ball, S. L., Holland, A. J., Huppert, F. A., Trep- conditions associated with dementia di- pner, P., Watson, P., & Hon, J. (2004). The agnosis. Journal of Policy and Practice modified CAMDEX informant interview is in Intellectual Disabilities, 2(1), 47–56. a valid and reliable tool for use in the di- doi:10.1111/j.1741-1130.2005.00007.x agnosis of dementia in adults with Down’s Cooper, S.-A. (1997). High prevalence of demen- syndrome. Journal of Intellectual Disabil- tia among people with learning disabili- Chapter 25 Neurocognitive Disorders 593

ties not attributable to Down’s syndrome. velopmental Disability, 23(1), 13–24. Psychological Medicine, 27(03), 609–616. doi:10.1080/13668259800033551 doi:10.1017/S0033291796004655 Deb, S. (2003). Dementia in people with an in- Cooper, S.-A., & Prasher, V. P. (1998). Maladap- tellectual disability. Reviews in Clinical tive behaviours and symptoms of dementia Gerontology, 13(2), 137–144. doi:10.1017/ in adults with Down’s syndrome compared S095925980301325X with adults with intellectual disability of Deb, S., Hare, M., & Prior, L. (2007). Symptoms other aetiologies. Journal of Intellectu- of dementia among adults with Down’s syn- al Disability Research, 42(4), 293–300. drome: A qualitative study. Journal of Intel- doi:10.1046/j.1365-2788.1998.00135.x lectual Disability Research, 51(Pt 9), 726– Cooper, S.-A., Smiley, E., Morrison, J., William- 739. doi:10.1111/j.1365-2788.2007.00956.x son, A., & Allan, L. (2007). Mental ill-health Deb, S., Hare, M., Prior, L., & Bhaumik, S. in adults with intellectual disabilities: Prev- (2007). Dementia screening questionnaire alence and associated factors. The Brit- for individuals with intellectual disabilities. ish Journal of Psychiatry: The Journal of The British Journal of Psychiatry, 190(5), Mental Science, 190, 27–35. doi:10.1192/bjp. 440–444. doi:10.1192/bjp.bp.106.024984 bp.106.022483 Deb, S., & McHugh, R. (2010). Dementia among Coppus, A., Evenhuis, H., Verberne, G.-J., Viss- persons with Down syndrome. Interna- er, F., Van Gool, P., Eikelenboom, P., & tional Review of Research in Mental Re- Van Duijin, C. (2006). Dementia and mor- tardation, 39, 221–255. doi:10.1016/S0074- tality in persons with Down’s syndrome. 7750(10)39008-2 Journal of Intellectual Disability Re- Devenny, D. A., Krinsky-McHale, S. J., Sersen, search, 50(10), 768–777. doi:10.1111/j.1365- G., & Silverman, W. P. (2000). Sequence of 2788.2006.00842.x cognitive decline in dementia in adults with Coppus, A. M. W., Schuur, M., Vergeer, J., Jans- Down’s syndrome. Journal of Intellectual sens, A. C. J. W., Oostra, B. A., Verbeek, M. M., Disability Research, 44 ( Pt 6), 654–665. … M, C. (2012). Plasma amyloid and the risk Devenny, D. A., Zimmerli, E. J., Kittler, P., & of Alzheimer’s disease in Down syndrome. Krinsky-McHale, S. J. (2002). Cued recall in Neurobiology of Aging, 33(9), 1988–1994. early-stage dementia in adults with Down’s doi:10.1016/j.neurobiolaging.2011.08.007 syndrome. Journal of Intellectual Disabil- Courtenay, K., Jokinen, N. S., & Strydom, A. ity Research, 46(6), 472–483. doi:10.1046/ (2010). Caregiving and adults with intellec- j.1365-2788.2002.00417.x tual disabilities affected by dementia. Jour- Dodd, K., Bhaumik, S., & Benbow, S. M. (2009, nal of Policy and Practice in Intellectual September). Dementia and people with learn- Disabilities, 7(1), 26–33. doi:10.1111/j.1741- ing disabilities: Guidance on the assessment, 1130.2010.00244.x diagnosis, treatment and support of people Crayton, L., Oliver, C., Holland, A., Bradbury, with learning disabilities who develop de- J., & Hall, S. (1998). The neuropsycho- mentia. British Psychological Society. logical assessment of age related cogni- Esbensen, A. J., Mailick, M. R., & Silverman, tive deficits in adults with Down’s syn- W. (2013). Long-term Impact of parental drome. Journal of Applied Research in well-being on adult outcomes and dementia Intellectual Disabilities, 11(3), 255–272. status in individuals with Down syndrome. doi:10.1111/j.1468-3148.1998.tb00066.x American Journal on Intellectual and De- Dalton, A. J., & Fedor, B. L. (1998). On- velopmental Disabilities, 118(4), 294–309. set of dyspraxia in aging persons with doi:10.1352/1944-7558-118.4.294 Down syndrome: Longitudinal stud- Evans, E., Bhardwaj, A., Brodaty, H., Sachdev, ies. Journal of Intellectual and De- P., Draper, B., & Trollor, J. N. (2013). Demen- 594 DM-ID-2 Textbook

tia in people with intellectual disability: Hermans, H., & Evenhuis, H. M. (2013). Factors Insights and challenges in epidemiological associated with depression and anxiety in research with an at-risk population. In- older adults with intellectual disabilities: ternational Review of Psychiatry, 25(6), Results of the healthy ageing and intellectu- 755–763. doi:10.3109/09540261.2013.866938 al disabilities study. International Journal Evenhuis, H. M. (1992). Evaluation of a screening of Geriatric Psychiatry, 28(7), 691–699. instrument for dementia in ageing mentally doi:10.1002/gps.3872 retarded persons. Journal of Intellectual Herron, D. L., & Priest, H. M. (2013). Support Disability Research, 36 ( Pt 4), 337–347. workers’ knowledge about dementia: A vi- Evenhuis, H. M. (1997). The natural history of gnette study. Advances in Mental Health dementia in ageing people with intellectual and Intellectual Disabilities, 7(1), 27–39. disability. Journal of Intellectual Disabili- doi:10.1108/20441281311294675 ty Research, 41 ( Pt 1), 92–96. Holland, A. J., Hon, J., Huppert, F. A., & Stevens, Evenhuis, H. M., Theunissen, M., Denkers, I., F. (2000). Incidence and course of dementia Verschuure, H., & Kemme, H. (2001). Prev- in people with Down’s syndrome: Findings alence of visual and hearing impairment in from a population-based study. Journal of a Dutch institutionalized population with Intellectual Disability Research, 44 ( Pt intellectual disability. Journal of Intellec- 2), 138–146. tual Disability Research, 45(5), 457–464. Holland, A. J., Hon, J., Huppert, F. A., Stevens, doi:10.1046/j.1365-2788.2001.00350.x F., & Watson, P. (1998). Population-based Fleminger, S., Oliver, D. L., Lovestone, S., Ra- study of the prevalence and presentation of be-Hesketh, S., & Giora, A. (2003). Head in- dementia in adults with Down’s syndrome. jury as a risk factor for Alzheimer’s disease: The British Journal of Psychiatry, 172(6), The evidence 10 years on; a partial replica- 493–498. doi:10.1192/bjp.172.6.493 tion. Journal of Neurology, Neurosurgery, Jamieson-Craig, R., Scior, K., Chan, T., Fenton, and Psychiatry, 74(7), 857–862. C., & Strydom, A. (2010). Reliance on car- Haveman, M., Heller, T., Lee, L., Maaskant, M., er reports of early symptoms of dementia Shooshtari, S., & Strydom, A. (2010). Major among adults with intellectual disabilities. health risks in aging persons with intel- Journal of Policy and Practice in Intellec- lectual disabilities: An overview of recent tual Disabilities, 7(1), 34–41. doi:10.1111/ studies. Journal of Policy and Practice j.1741-1130.2010.00245.x in Intellectual Disabilities, 7(1), 59–69. Kannabiran, M., & Deb, S. (2010). Diseases of doi:10.1111/j.1741-1130.2010.00248.x the nervous system II: Neurodegenera- Haveman, M., Perry, J., Salvador-Carulla, L., tive diseases including dementias. In J. Walsh, P. N., Kerr, M., Van Schrojenstein O’Hara, J. McCarthy, & N. Bouras (Eds.), Lantman-de Valk, H., … Weber, G. (2011). Intellectual disability and ill health (pp. Ageing and health status in adults with 203-213). Cambridge University Press. intellectual disabilities: Results of the Eu- Retrieved from http://dx.doi.org/10.1017/ ropean POMONA II study. Journal of Intel- CBO9780511770715.021 lectual & Developmental Disability, 36(1), Kittler, P., Krinsky-McHale, S. J., & Devenny, 49–60. doi:10.3109/13668250.2010.549464 D. A. (2006). Verbal intrusions precede Head, E., Doran, E., Nistor, M., Hill, M., Schmitt, memory decline in adults with Down syn- F. A., Haier, R. J., & Lott, I. T. (2011). Plasma drome. Journal of Intellectual Disability amyloid-β as a function of age, level of intel- Research: JIDR, 50(Pt 1), 1–10. doi:10.1111/ lectual disability, and presence of dementia j.1365-2788.2005.00715.x in Down syndrome. Journal of Alzheimer’s Knopman, D. S., DeKosky, S. T., Cummings, J. Disease, 23(3), 399–409. doi:10.3233/JAD- L., Chui, H., Corey–Bloom, J., Relkin, N., … 2010-101335 Stevens, J. C. (2001). Practice parameter: Chapter 25 Neurocognitive Disorders 595

Diagnosis of dementia (an evidence-based Määttä, T., Määttä, J., Tervo-Määttä, T., Taanila, review). Report of the Quality Standards A., Kaski, M., & Iivanainen, M. (2011). Health- Subcommittee of the American Academy care and guidelines: A population-based of Neurology. Neurology, 56(9), 1143–1153. survey of recorded medical problems and doi:10.1212/WNL.56.9.1143 health surveillance for people with Down Krinsky-McHale, S. J., Devenny, D. A., & Sil- syndrome. Journal of Intellectual and De- verman, W. P. (2002). Changes in explicit velopmental Disability, 36(2), 118–126. do memory associated with early dementia in i:10.1080/13668250.2011.570253 adults with Down’s syndrome. Journal of Matsuoka, Y., Andrews, H. F., Becker, A. G., Gray, Intellectual Disability Research, 46(Pt 3), A. J., Mehta, P. D., Sano, M. C., … Aisen, P. 198–208. S. (2009). The relationship of plasma Abe- Krinsky-McHale, S. J., & Silverman, W. (2013). ta levels to dementia in aging individuals Dementia and mild cognitive impairment in with Down syndrome. Alzheimer’s disease adults with intellectual disability: Issues of and Associated Disorders, 23(4), 315–318. diagnosis. Developmental Disabilities Re- doi:10.1097/WAD.0b013e3181aba61e search Reviews, 18(1), 31–42. doi:10.1002/ McCarron, M., Gill, M., McCallion, P., & Begley, ddrr.1126 C. (2005). Health co-morbidities in ageing Lin, J.-D., Lin, L.-P., Hsia, Y.-C., Hsu, S.-W., Wu, C.- persons with Down syndrome and Alzhei- L., & Chu, C. M. (2014). A national survey of mer’s dementia. Journal of Intellectual caregivers’ perspective of early symptoms Disability Research: JIDR, 49(Pt 7), 560– of dementia among adults with an intellec- 566. doi:10.1111/j.1365-2788.2005.00704.x tual disability based on the DSQIID scale. McCarron, M., McCallion, P., Reilly, E., & Mulry- Research in Autism Spectrum Disorders, an, N. (2014). A prospective 14-year longitu- 8(3), 275–280. doi:10.1016/j.rasd.2013.12.010 dinal follow-up of dementia in persons with Lott, I. T., & Dierssen, M. (2010). Cognitive Down syndrome. Journal of Intellectual deficits and associated neurological com- Disability Research: JIDR, 58(1), 61–70. plications in individuals with Down’s syn- doi:10.1111/jir.12074 drome. Lancet Neurology, 9(6), 623–633. Möller, J. C., Hamer, H. M., Oertel, W. H., & doi:10.1016/S1474-4422(10)70112-5 Rosenow, F. (2001). Late-onset myoclonic Lott, I. T., Doran, E., Nguyen, V. Q., Tournay, epilepsy in Down’s syndrome (LOMEDS). A., Head, E., & Gillen, D. L. (2011). Down Seizure—European Journal of Epilepsy, syndrome and dementia: A randomized, 10(4), 303–306. doi:10.1053/seiz.2000.0500 controlled trial of antioxidant supplementa- Moog, U., van Mierlo, I., van Schrojenstein Lant- tion. American Journal of Medical Genet- man-de Valk, H. M. J., Spaapen, L., Maaskant, ics Part A, 155(8), 1939–1948. doi:10.1002/ M. A., & Curfs, L. M. G. (2007). Is Sanfilippo ajmg.a.34114 type B in your mind when you see adults with Lott, I. T., Doran, E., Nguyen, V. Q., Tournay, A., mental retardation and behavioral problems? Movsesyan, N., & Gillen, D. L. (2012). Down American Journal of Medical Genetics Part syndrome and dementia: Seizures and cogni- C: Seminars in Medical Genetics, 145C(3), tive decline. Journal of Alzheimer’s Disease, 293–301. doi:10.1002/ajmg.c.30142 29(1), 177–185. doi:10.3233/JAD-2012-111613 Moran, J. A., Rafii, M. S., Keller, S. M., Singh, Määttä, T., Kaski, M., Taanila, A., Keinänen-Ki- B. K., & Janicki, M. P. (2013). The national ukaanniemi, S., & Iivanainen, M. (2006a). task group on intellectual disabilities and Sensory impairments and health concerns dementia practices consensus recommen- related to the degree of intellectual disabil- dations for the evaluation and management ity in people with Down syndrome. Down of dementia in adults with intellectual dis- Syndrome Research and Practice, 11(2), abilities. Mayo Clinic Proceedings, 88(8), 78–83. doi:10.3104/reports.317 831–840. doi:10.1016/j.mayocp.2013.04.024 596 DM-ID-2 Textbook

Nelson, L. D., Orme, D., Osann, K., & Lott, I. T. heimer’s disease in adults with Down syn- (2001). Neurological changes and emotional drome: Meta-analysis. American Journal functioning in adults with Down syndrome. on Mental Retardation, 102(2), 103–110. Journal of Intellectual Disability Re- Prasher, V. P., Uppal, H., Parveen, S., Adams, C., search, 45(5), 450–456. doi:10.1046/j.1365- & Haque, S. (2013). Ten year serial mean 2788.2001.00379.x corpuscular volume—A peripheral marker Nelson, L., Johnson, J. K., Freedman, M., Lott, for Alzheimer’s disease in Down syndrome. I., Groot, J., Chang, M., … Head, E. (2005). International Journal of Geriatric Psy- Learning and memory as a function of chiatry, 28(10), 1097–1098. doi:10.1002/ age in Down syndrome: A study using gps.3956 animal-based tasks. Progress in Neu- Rapin, I., Weidenheim, K., Lindenbaum, Y., ro-Psychopharmacology and Biological Rosenbaum, P., Merchant, S. N., Krishna, Psychiatry, 29(3), 443–453. doi:10.1016/j. S., & Dickson, D. W. (2006). Cockayne syn- pnpbp.2004.12.009 drome in adults: Review with clinical and Oliver, C., Kalsy, S., McQuillan, S., & Hall, S. pathologic study of a new case. Journal of (2011). Behavioural excesses and deficits Child Neurology, 21(11), 991–1006. doi:10.11 associated with dementia in adults who 77/08830738060210110101 have Down syndrome. Journal of Ap- Rissman, R. A., & Mobley, W. C. (2011). Impli- plied Research in Intellectual Disabil- cation for treatment: GABAA receptors ities, 24(3), 208–216. doi:10.1111/j.1468- in aging, Down syndrome and Alzhei- 3148.2010.00604.x mer’s disease. Journal of Neurochemis- Patti, D. (1999). Cognitive changes in memory try, 117(4), 613–622. doi:10.1111/j.1471- precede those in praxis in aging persons 4159.2011.07237.x with Down syndrome. Journal of Intel- Silverman, W. P., Zigman, W. B., Krinsky-McHale, lectual & Developmental Disability, 24, S. J., Ryan, R., & Schupf, N. (2013). Intellec- 169–187. tual disability, mild cognitive impairment, Petersen, R. C. (2011). Mild cognitive impair- and risk for dementia. Journal of Policy ment. New England Journal of Medi- and Practice in Intellectual Disabilities, cine, 364(23), 2227–2234. doi:10.1056/NE- 10(3). doi:10.1111/jppi.12042 JMcp0910237 Skandar, A., Schoonbrood-Lenssen, A., Van Prasher, V. (1995). End-stage dementia in adults den Akker, M., & Maaskant, M. (2005). Ver- with Down syndrome. International Jour- ouderingskenmerken bij mensen met het nal of Geriatric Psychiatry, 10(12), 1067– syndroom van Sanfilippo.Tijdschrift Voor 1069. doi:10.1002/gps.930101213 Artsen Voor Verstandelijk Gehandicapten, Prasher, V., Farooq, A., & Holder, R. (2004). The 23(4), 3–5. Adaptive Behaviour Dementia Question- Sparrow, S. S. (2011). Vineland Adaptive Be- naire (ABDQ): Screening questionnaire for havior Scales. In J. S. Kreutzer, J. DeLuca, dementia in Alzheimer’s disease in adults & B. Caplan (Eds.), Encyclopedia of clin- with Down syndrome. Research in Devel- ical neuropsychology (pp. 2618–2621). opmental Disabilities, 25(4), 385–397. Springer New York. Retrieved from http:// doi:10.1016/j.ridd.2003.12.002 link.springer.com/referenceworken- Prasher, V. P. (1995). Age-specific prevalence, try/10.1007/978-0-387-79948-3_1602 thyroid dysfunction and depressive symp- Strydom, A., Chan, T., Fenton, C., Jamie- tomatology in adults with down syndrome son-Craig, R., Livingston, G., & Hassiotis, and dementia. International Journal A. (2013). Validity of criteria for dementia of Geriatric Psychiatry, 10(1), 25–31. in older people with intellectual disabil- doi:10.1002/gps.930100106 ity. The American Journal of Geriatric Prasher, V. P., Chowdhury, T. A., Rowe, B. R., & Psychiatry, 21(3), 279–288. doi:10.1016/j. Bain, S. C. (1997). ApoE genotype and Alz- jagp.2012.11.017 Chapter 25 Neurocognitive Disorders 597

Strydom, A., Chan, T., King, M., Hassiotis, A., Urv, T. K., Zigman, W. B., Silverman, W., & Ma- & Livingston, G. (2013). Incidence of de- cLean, J., William E. (2008). Maladaptive be- mentia in older adults with intellectual dis- haviors related to dementia status in adults abilities. Research in Developmental Dis- with Down syndrome. American Journal abilities, 34(6), 1881–1885. doi:10.1016/j. on Mental Retardation, 113(2), 73–86. ridd.2013.02.021 doi:10.1352/0895-8017(2008)113[73:M- Strydom, A., Hassiotis, A., King, M., & Living- BRTDS]2.0.CO;2 ston, G. (2009). The relationship of demen- Visser, F. E., Aldenkamp, A. P., van Huffelen, A. tia prevalence in older adults with intellec- C., Kuilman, M., Overweg, J., & van Wijk, J. tual disability (ID) to age and severity of (1997). Prospective study of the prevalence ID. Psychological Medicine, 39(01), 13–21. of Alzheimer’s-type dementia in institution- doi:10.1017/S0033291708003334 alized individuals with Down syndrome. Strydom, A., Livingston, G., King, M., & Hassi- American Journal on Mental Retardation, otis, A. (2007). Prevalence of dementia in intellectual disability using different diag- 101(4), 400–412. nostic criteria. The British Journal of Psy- Whitwham, S., McBrien, J., & Broom, W. (2011). chiatry, 191(2), 150–157. doi:10.1192/bjp. Should we refer for a dementia assessment? bp.106.028845 A checklist to help know when to be con- Strydom, A., Shooshtari, S., Lee, L., Raykar, V., cerned about dementia in adults with Down Torr, J., Tsiouris, J., … Maaskant, M. (2010). syndrome and other intellectual disabil- Dementia in older adults with intellectual ities. British Journal of Learning Dis- disabilities—Epidemiology, presentation, abilities, 39(1), 17–21. doi:10.1111/j.1468- and diagnosis. Journal of Policy and Prac- 3156.2009.00606.x tice in Intellectual Disabilities, 7(2), 96– Zeilinger, E. L., Stiehl, K. A. M., & Weber, G. 110. doi:10.1111/j.1741-1130.2010.00253.x (2013). A systematic review on assessment Torr, J., Strydom, A., Patti, P., & Jokinen, N. instruments for dementia in persons with (2010). Aging in Down syndrome: Morbid- intellectual disabilities. Research in Devel- ity and mortality. Journal of Policy and opmental Disabilities, 34(11), 3962–3977. Practice in Intellectual Disabilities, 7(1), doi:10.1016/j.ridd.2013.08.013 70–81. doi:10.1111/j.1741-1130.2010.00249.x Zigman, W. B. (2013). Atypical aging in Down Tyrrell, J., Cosgrave, M., McCarron, M., McPher- syndrome. Developmental Disabilities Re- son, J., Calvert, J., Kelly, A., … Lawlor, B. A. search Reviews, 18(1), 51–67. doi:10.1002/ (2001). Dementia in people with Down’s syn- ddrr.1128 drome. International Journal of Geriatric Psychiatry, 16(12), 1168–1174. doi:10.1002/ Zigman, W. B., Schupf, N., Devenny, D. A., gps.502 Miezejeski, C., Ryan, R., Urv, T. K., … Silver- Urv, T. K., Zigman, W. B., & Silverman, W. (2010). man, W. (2004). Incidence and prevalence Psychiatric symptoms in adults with Down of dementia in elderly adults with men- syndrome and Alzheimer’s disease. Amer- tal retardation without Down syndrome. ican Journal on Intellectual and Devel- American Journal on Mental Retardation, opmental Disabilities, 115(4), 265–276. 109(2), 126–141. doi:10.1352/0895-8017(200 doi:10.1352/1944-7558-115.4.265 4)109<126:IAPODI>2.0.CO;2 598 DM-ID-2 Textbook