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Advances in psychiatric treatment (2012), vol. 18, 144–153 doi: 10.1192/apt.bp.110.008268

ARTICLE in Raghavakurup Radhakrishnan, Robert Butler & Laura Head

Raghavakurup Radhakrishnan domains, including current IQ, category fluency, Summr a y is an ST6 in at verbal , abstract thinking, , St Clement’s Hospital, Ipswich. A growing body of evidence suggests that the most sustained and response inhibition. His research interests include common type of dementia in schizophrenia differs and memory in dementia, Symbol coding tasks yielded some of the most from Alzheimer’s in its clinical features, , schizophrenia in late robust evidence, with very large effect sizes. natural course, neuropathology, neuroanatomical life and cognitive functioning after However, Hyde et al (1994) performed a cross- electroconvulsive therapy. Robert substrates and . Furthermore, there Butler is a consultant old age is some evidence that the risk of developing sectional study to assess cognitive performance with Suffolk Mental cognitive impairment and its progression in early- in schizophrenia across a wide age range. A Partnership NHS Trust, at onset schizophrenia differ compared with late- or comparison of scores on cognitive measures St Clement’s Hospital, Ipswich. very-late-onset schizophrenia. The diagnosis recorded for five age-derived cohorts showed His interests include dementia, depression in later life and service and management of dementia in schizophrenia no evidence of accelerated decline on the Mini- provision. Laura Head is a is challenging for both general adult and old age Mental State Examination (MMSE), the Dementia consultant old age psychiatrist with . This article reviews the evidence Rating Scale, list , semantic fluency Suffolk Partnership base regarding dementia in schizophrenia. It or perseverative errors on the Wisconsin Card NHS Trust, working at Minsmere discusses the diagnosis of dementia in schizo­ Sorting Test. House, Ipswich. Her interests phrenia, its management and prognosis, and include crisis and in-patient care identifies some future research opportunities. of older people with mental health Do people with schizophrenia develop problems, and medical management. D eCLARATIon of interest Correspondence Dr Robert Butler, dementia? Consultant Old Age Psychiatrist, L. H. has undertaken commercial trials. In his Lehrbuch der Psychiatrie of 1893, Kraepelin St Clement’s Hospital, Foxhall used the term ‘’ (premature Road, Ipswich IP3 8LS, UK. Email: dementia) for schizophrenia because of its onset [email protected] Cognitive impairment is a well-recognised and in early life and the characteristic development cardinal feature of schizophrenia (Keefe 2007). of ‘mental enfeeblement’. He emphasised the Given the biological effects of on the progressive deterioration of cognition but noted brain, it is important to consider the cognitive that memory was spared. He distinguished this manifestations of schizophrenia in the context condition from paraphrenia in which cognitive of ageing. Significant issues include the natural impairment did not occur. history of cognitive dysfunction over the lifespan, Over a century later, there is uncertainty about its progression to dementia, and the temporal the course of cognitive function with ageing in relationship between and cognitive schizophrenia. Early studies of the progression deficits. In this context, it helps to have a precise of dementia over the lifespan in individuals definition of cognitive impairment, and we find the with schizophrenia have shown inconsistent following useful: ‘a level of cognitive functioning results, although they were limited by a lack of suggesting a consistent severe impairment and/ standardised diagnostic criteria and specific or a significant decline from premorbid levels evaluation techniques. considering patients’ educational, familial In a study of long-term in-patients with schizo­ and socioeconomic background’ (Keefe 2007). phrenia who had survived into old age, Harvey Cognitive impairment has a trajectory over the et al (1999a) followed up a group for 30 months course of schizophrenia that is different from using the (CDR). Over that of psychotic symptoms and it may contribute this period, 30% of the patients deteriorated, to a poor functional outcome in older patients from a baseline of minimal or mild cognitive and (Davidson 1995). functional impairment to impairments severe enough to warrant a secondary diagnosis of Cognitive impairment in schizophrenia dementia. A number of meta-analyses have examined the Although many studies suggest a model of extent of cognitive impairment in people with schizophrenia as a progressive dementing illness, schizophrenia (Heinrichs 1998; Aleman 1999; others have supported the view that cognitive Bokat 2003). Large effect sizes (between 1 and impairment in schizophrenia fits the model of 1.5), representing robust evidence of impairment, a static (Goldberg 1993; Hyde have been reported across a multitude of cognitive 1994).

144 Advances in psychiatric treatment (2012), vol. 18, 144–153 doi: 10.1192/apt.bp.110.008268 Dementia in schizophrenia

Evidence from international studies despite low MMSE scores at initial assessment. The authors concluded that cognitive functioning Studies examining cognitive impairment in older in older people with schizophrenia is different people with schizophrenia from that seen in Alzheimer’s disease. Ciompi (1980) described evaluations of mostly Heaton et al (1994) compared three groups of elderly people surviving from a large sample of people with schizophrenia (young people with patients with schizophrenia. He estimated that early-onset schizophrenia, older people with early- 25% had moderate to severe cognitive deficits, onset disorder, and people with late-onset, i.e. including memory disturbance and disorientation. after age 45, disorder) with ambulatory patients This study of chronically institutionalised older with Alzheimer’s disease and normal controls. patients demonstrated the presence of age- They concluded that cognitive impairment in related impaired global cognitive performance as schizophrenia is unrelated to current age, age at measured by the MMSE. Other researchers have onset or duration of illness. They also suggested estimated that more than 80% of older people that there is an encephalopathy associated with with schizophrenia show significant cognitive schizophrenia that is non-progressive and that impairment (Keefe 2007). has a different pattern of deficits from that seen in Studies showing a significant decline in cognition Alzheimer’s disease. over time The risk of dementia in late-onset and very-late- In a re-evaluation of the IOWA 500 study of a onset schizophrenia cohort of people with hebephrenic or catatonic schizo­phrenia followed up for 40 years, Winokur Late-onset schizophrenia is usually defined as et al (1987) found that the subgroup of older onset after 40 years of age, and very-late-onset as participants was significantly more likely to have after 60 years of age. Studies of schizophrenia of worsened orientation and memory. late and very late onset are few and inconsistent In a follow-up of older patients with schizo­ in their results. phrenia after discharge from long-term care in Palmer et al (2003) compared changes in cog­ , Harvey et al (1999b) noted nition over 1 and 2 years for out-patients with an average reduction of 3.8 points on the MMSE late-onset schizophrenia-spectrum disorders, over a period of 2.5 years. Friedman et al (2001) earlier-onset schizophrenia-spectrum disorders, evalu­ated the cognitive and functional status Alzheimer’s disease with psychosis, or Alzhei­ of people with schizophrenia aged between 20 mer’s disease with baseline MMSE scores and 80 years in a 6-year follow-up study, and >25, and healthy comparison participants. compared the sub­group of patients aged 50 and Cognitive changes among participants in the two over with healthy individuals and patients with schizophrenia- groups were Alzheimer’s disease, also aged 50 and over. They similar to those in the healthy controls, whereas measured cognitive and functional decline using both Alzheimer’s disease groups showed greater CDR scores. They found a significant age-group declines in cognition. The authors concluded that effect on the magnitude of cognitive decline for late-onset schizophrenia is a neurodegenerative participants with schizophrenia. For those under disorder and, in agreement with earlier studies, a the age of 65, the proportional risk of cognitive and static encephalopathy. functional decline in schizophrenia was negligible. In another study (Laks 2006), involving a small However, the proportional risk rose from 38% for number of Brazilian patients with late-onset those aged 65–70, to 75% for the 70–75 age group schizophrenia, none of the participants developed and reached 100% for those aged 75–80. Neither observable dementia during 1-year follow-up. prior leucotomy, electroconvulsive therapy (ECT) Cognition and activities of daily living remained or coma therapy, nor current exposure to stable over the course of the year. However, a showed adverse effects on current longer-term Australian follow-up study, also with a cog­nitive functioning. The limitations of this study small sample size, produced very different results. included the use of relatively non-specific measures Brodaty et al (2003) compared patients with onset (MMSE and CDR) and the fact that the patients of schizophrenia at the age of 50 years or over, but had been institutionalised for long periods. without dementia, with a healthy control group. All participants were assessed at baseline, after 1 year Studies showing a lesser decline in cognition and after 5 years on measures of , An early study of older in-patients with schizo­ cognition and general functioning. At the 5-year phrenia (Harvey 1995) demonstrated that follow-up, 47% of participants in the schizophrenia cognitive changes were very slow over time, group met the criteria for dementia, for which the

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most common diagnosis was Alzheimer’s disease. Box 2 Post-mortem evidence None of the control group had dementia.

In a case-register study in Denmark, Kørner • Most people with schizophrenia and moderate to et al (2009) followed up a very large sample of severe cognitive impairment do not have Alzheimer’s first-contact patients with late- and very-late-onset disease pathology

schizophrenia for between 3 and 4.6 years. They • Post-mortem studies have generally not found an compared these individuals with two age-matched increased incidence of Alzheimer’s disease in people control groups: patients with osteoarthritis with schizophrenia and a sample of the general population. After 3–4.6 years, the risk of receiving a diagnosis of dementia was two to three times higher for the Purohit et al (1993) studied the presence of schizophrenia group than for the control groups. senile plaques and neurofibrillary tangles in Among the participants who developed dementia the post-mortem brains of a small number of during follow-up, the most common diagnosis elderly patients with schizophrenia and cognitive in the schizophrenia group was unspecified impairment, comparing them with the brains of dementia, whereas in the general population and age-matched patients with Alzheimer’s disease. It osteoarthritis groups it was Alzheimer’s disease. was noted that none of the brains from the group This Danish study suggests that, although people with schizophrenia showed a sufficient degree with late-onset and very-late-onset schizophrenia of senile plaques and neurofibrillary tangles to have an increased risk of developing dementia, it make the diagnosis of Alzheimer’s disease. Despite does not seem to be due to an increased risk of advanced age and cognitive impairment, however, developing Alzheimer’s disease, thus pointing to the density of senile plaques was sparse in the the possibility that they are developing a different majority of samples from the schizophrenia group. type of dementia. The authors concluded that cognitive impairment Box 1 summarises the evidence from inter­ cannot be explained by increased vulnerability national studies. to Alzheimer’s disease. Other (mostly small- sample) studies using immuno­histochemistry N europathology and post-mortem evidence have failed to show any increased incidence of Kørner et al ’s (2009) finding of an increased risk Alzheimer’s disease pathology in people dying of developing dementia in their schizophrenia with schizophrenia and cognitive impairment. cohort might be explained by confounding A subsequent study by Purohit et al (1998) diagnostic factors. For example, Alzheimer’s examined 100 consecutive brains from disease or might have presented patients with schizophrenia, and compared atypically or have been undiagnosed by clinicians them with the brains from normal controls and reluctant to make a diagnosis in the context of from patients with non-schizophrenic psychoses. schizophrenia. People with schizophrenia often In previous cognitive assessments, 72% of the have unhealthy lifestyles and inadequate physical patients with schizophrenia had shown moderate healthcare, both of which are vascular risk factors to severe cognitive impairment. However, post- for Alzheimer’s disease and vascular dementia. mortem examination revealed that only 9% met However, post-mortem neuropathological studies neuropathological criteria for Alzheimer’s disease. do not support this hypothesis. This study demonstrates that, although severe cognitive impairment is commonly observed in schizophrenia, it is only occasionally due to Box 1 Cognitive impairment in schizophrenia comorbid Alzheimer’s disease. The findings from post-mortem studies are • Cognitive impairment is a feature of schizophrenia summarised in Box 2. • Over 25% of older people with schizophrenia have If the pathology is not that of Alzheimer’s disease, moderate to severe cognitive impairment what is its neuropathological basis? Most dementia • Most studies have found a significant decline in in schizophrenia is not characterised by classic, cognition over time in schizophrenia histologically identifiable neuropathology and

• Conversely, some studies have found cognitive most is probably not the result of an identifiable impairment to be relatively stable in schizophrenia dementing illness.

• The proportion of people who develop dementia in later life among those with schizophrenia appears to be N eurochemistry higher than in the general population A number of neurochemical abnormalities have been identified in cognitively impaired patients

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with schizophrenia. Although some of these are Box 3 Clinical diagnosis shared with Alzheimer’s disease, many are not.

For example, cortical somatostatin and • Always assess cognition in people with schizophrenia levels are similar in schizophrenia and Alzheimer’s • From the history, establish the pattern of cognitive disease, whereas cortical corticotrophin- impairment and level of functioning over time regulating hormone and acetylcholine levels are • Establish whether cognitive impairment fluctuates dissimilar. Cognitively impaired patients with with psychotic symptoms (less likely to be a dementia) schizo­phrenia show cortical deficits of vaso­ or shows a slow, steady decline (more likely to be a active intestinal peptide and neuropeptide Y, dementia) and increased senile plaque concentrations in the cingulate and temporal cortex (Powchik 1998). In addition, there is some evidence of a reduction in later life. The question of whether longitudinal in concentrations of serotonin and noradrenaline assessments of cognitive function would have in cognitive impairment. It has also been shown predictive value needs further research. that people with a diagnosis of schizophrenia and The correct diagnosis of dementia in people dementia without Alzheimer’s disease do not show with schizophrenia (Box 3) is largely dependent significantly elevated levels of b-peptide, on the expertise and skill of the clinician carrying which is increased in the post-mortem brains out the assessment. However, the measurement of Alzheimer’s disease patients (Religa 2003). of cognitive function required to inform the This last study suggested that antipsychotics diagnosis raises a vexing question: What tools, may actually protect against the development of measures and approaches should the clinician Alzheimer’s disease pathology. use to assess cognition? To complicate matters further, cognitive decline, a core feature of both Diagnosis schizophrenia and dementia, is found to some The assessment of people with schizophrenia pre­ extent in normal ageing. Moreover, all these senting with features of dementia can be difficult evaluations require the patient’s cooperation. for several . First of all, it can be clearly demonstrated that a substantial percentage of Assessment of cognitive function people with schizophrenia develop cognitive Many studies have shown that the MMSE (Folstein dysfunction early in their illness, so a retrospective 1975) is not adequate to pick up cognitive deficits history may not give a clear-cut picture of recent in complex disorders such as schizophrenia. There changes. However, a detailed history from both is evidence that the MMSE scores of people with the patient and an informant with close personal schizophrenia remain relatively stable over time knowledge of them over time may reveal a pattern (Harvey 1995; Brodaty 2003; Palmer 2003). It will of increasing cognitive decline. The history and therefore take a long time for changes in cognitive assessment should include orientation, memory, function to become apparent using this measure. personality changes and activities of daily The MATRICS Consensus Cognitive Battery living. Effective cognitive testing is essential on (MCCB) assesses seven putatively separable presentation, as is information about the patient’s domains of cognitive dysfunction in schizophrenia previous level of functioning. (Kern 2008; Nuechterlein 2008). In an ideal Diagnosis at this stage would be made easier if world, this tool could be used with every patient. cognitive testing early in the lifespan of patients However, practical and economic constraints with schizophrenia were routine. There is a growing facing many clinics and treatment settings consensus that cognitive deficits characterising make this unfeasible. Studies have shown that schizophrenia should be incorporated into the impairments on digit–symbol substitution tasks major diagnostic systems, including the DSM have the largest effect sizes among many different and ICD (Bora 2010). Such a development would measures for characterising cognitive impairment prompt clinicians to assess a patient’s cognitive in schizophrenia. profile early in the course of schizophrenia. This, Another consideration is whether it is necessary in turn, might stimulate new treatment methods to carry out a formal assessment of cognition, given and promote better management of cognitive that many clinicians will not have any experience impairment and dementia in schizophrenia. in administering such measures. Scales such as The emphasis should be on recognising whether the Schizophrenia Cognition Rating Scale (Keefe cognitive deficits have been stable over time 2006) may be easier for clinicians to administer or there has been a significant decline from a as they are similar in format to a traditional premorbid level of cognitive function, particularly diagnostic assessment.

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Tools designed for use in Alzheimer’s disease feasible to use scales in every case. It may be more may be useful for the assessment of cognitive appropriate to take a detailed history and carry deterioration in schizophrenia. These include out a brief cognitive assessment in all cases and the Consortium to Establish a Registry for to reserve specific tools for patients with difficult Alzheimer’s Disease (CERAD) neuro­psychological presentations. battery (Morris 1989) and the cognitive subscale of the Alzheimer’s Disease Assessment Scale – Assessment of social and occupational Late version (ADAS-L Cog). The CERAD battery functioning is designed to measure all aspects of cognitive Both DSM-IV and ICD-10 diagnostic criteria for functioning, whereas the ADAS-L Cog is specific dementia include impaired social and occu­pational to late-stage Alzheimer’s dementia. functioning. It is therefore necessary to establish a A study involving a sample of elderly patients decline in social functioning to make a diagnosis with schizophrenia (Bowie 2002) concluded that of dementia. However, such impairment may also the ADAS-L Cog reliably and validly assesses occur as negative symptoms of schizophrenia, and cognition in the presence of severe cognitive the differentiation of negative symptoms from a impairment. The authors felt that the CERAD functional decline needs careful assessment. The battery was not adequate in a particularly low- Positive and Negative Scale (PANSS; functioning population. Kay 1987) may be useful for the identification Zakzanis et al (2003) conducted neuropsycho­ of negative symptoms. The Social Adaptive logical assessments to identify the best tests to Functioning Evaluation (SAFE) scale (Harvey distinguish between Alzheimer’s disease and 1997) is a 17-item scale that measures social– late-onset schizophrenia. Results showed that interpersonal, instrumental and impulse-control the similarities subtest of the Wechsler Adult deficits and it has a high interrater reliability. Intelligence Scale – Revised (Wechsler 1981) and These tools may be particularly useful for patient the California Verbal Learning Test (Delis 1987) follow-up and for developing treatment strategies. are particularly suitable. The Milan Overall Dementia Assessment Brain imaging and diagnosis (MODA; Brazzelli 1994) has also been used Technological advances have led to a greater use to assess cogni­tive impairment in people with of structural and functional brain imaging to schizophrenia (Lepore 2009). It was found to be assist with the diagnosis of dementia in people a valid tool for identify­ing cases of dementia in with evidence of cognitive decline. Additional this group, and results were not influenced by an information obtained from these investigations individual’s age or level of education. The authors helps clinicians to make an accurate diagnosis and recommended that the MODA might be useful in formulate a treatment plan. In clinical practice, routine clinical practice. structural magnetic resonance imaging (MRI) and The use of such tools (Box 4) in the assessment computed tomography (CT) scanning are widely of patients is more time-consuming than routine used, and radiologists interpret results on the clinical evaluation. Consequently, it may not be basis of visual . Structural imaging is often carried out to Box 4 Cognitive testing identify potentially treatable causes of dementia, such as normal pressure or space- • Assess a broad range of cognition, including memory occupying lesions, or to clarify the diagnosis by (short- and long-term), orientation, concentration, detecting cerebral () or patterns language, praxis and executive function of . In cognitively impaired patients without • The MMSE has limitations but is better than using no a definite clinical diagnosis, MRI may be helpful in scale reaching a diagnosis. Without MRI investigation • Slightly longer scales such as the ADAS-L Cog and the clinical diagnosis of vascular dementia may be Addenbrooke’s Cognitive Examination – Revised unreliable. Image analysis programs that quantify (ACE-R; Mioshi 2006)) give more useful information regional volumes in MRI (and CT) have shown • There are specific tools for dementia and schizophrenia, that measures of medial temporal or hippocampal such as the MATRICS atrophy can distinguish people with Alzheimer’s • There are specific tools for Alzheimer’s disease, such as disease from controls. Several studies have shown the CERAD ventricular enlargement, cerebral or • There are specific tools for the negative features of ischaemic change using CT or MRI schizophrenia, such as the PANSS scans. However, these findings are non-specific in both Alzheimer’s disease and vascular dementia.

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The results of CT investigation of brain structure Box 5 Brain imaging in schizophrenia have been variable. The most

consistent finding has been lateral ventricular • If the clinical assessment suggests an organic cause of enlargement, although the cause of this remains cognitive decline, CT and MRI are useful for excluding unclear. Computed tomography and MRI could normal pressure hydrocephalus, tumour and subdural give an into biological abnormalities in haematoma

patients with schizophrenia and dementing illness, • CT and MRI changes are non-specific in schizophrenia; but studies are limited in this group. Förstl et al ventricular enlargement is the most common finding

(1994) compared CT scans of patients with late- • CT and MRI changes are also non-specific in onset paranoid psychosis with those of patients Alzheimer’s disease and vascular dementia; atrophy with Alzheimer’s disease and of elderly controls and small-vessel changes respectively are the most with dementia. They found that the ventricles common findings, but these also occur in healthy older and anterior and Sylvian fissures of the psychosis people group were larger than in the controls but smaller • Little is known about functional imaging (SPECT, PET or than in those with Alzheimer’s dementia. However, fMRI) in this area. these non-specific findings alone do not help the clinician to distinguish dementia in schizophrenia from dementia due to Alzheimer’s disease or in the UK requires the early identification and or, indeed, to distinguish people management of dementia and the active inclusion with dementia from those without. of people with dementia in the decision-making Functional imaging technologies such as single- process (Department of Health 2001). However, photon emission computed tomography (SPECT), there are only a few high-quality evaluations of positron emission tomography (PET) and functional models of care in dementia (National Collaborating MRI (fMRI) also provide information about brain Centre for Mental Health 2011), and even these structure, but their spatial resolution is lower than show a particular lack of data from user and carer with CT or structural MRI. The added value of perspectives. functional scanning is the information provided on The Royal College of Psychiatrists (2006) has cerebral blood flow or glucose metabolism, even made recommendations for service provision for when structural deficits are not present. This can younger people with dementia. A study comparing help the physician in the diagnosis and differential old age psychiatrists and neurologists found that diagnosis of dementia (Silverman 2001). Patients younger patients may be underinvestigated if with Alzheimer’s disease typically show parietal, solely managed by old age psychiatrists, and may temporal, posterior cingulate and frontal deficits, not receive adequate follow-up if managed by whereas those with show neurologists (Cordery 2002). On the whole, old frontal and temporal deficits (Silverman 2001). age psychiatrists may be best equipped to manage Dementia with Lewy bodies has a pattern similar these patients, provided that they work in close to that of Alzheimer’s disease, but with additional collaboration with the appropriate specialists, for occipital deficits. However, there are no studies of example neurologists. dementia associated with schizophrenia. As the clinical use of neuro­imaging techniques expands, investigators are exploring novel appli­ Box 6 Management cations of existing techniques and developing • General adult mental health services have expertise others that measure various biological processes at managing schizophrenia, whereas older people’s relevant to neuro­degeneration. Combining neuro­ services specialise in managing dementia imaging studies with other procedures that provide • Memory clinics do not usually have the expertise data on genetic risk and measures from to manage people with schizophrenia and cognitive other tissues (e.g. blood serum, cerebrospinal impairment fluid) might increase diagnostic sensitivity and • Antipsychotics usually improve cognition if the specificity, as well as the predictive value of the impairment is associated with psychotic symptoms information. • Antipsychotics are contraindicated in people with For a summary of this section, see Box 5. primary dementia and non-cognitive symptoms of dementia, because of the increased risk of strokes and M anagement death

A major issue in the management of dementia in • Acetylcholinesterase inhibitors may be helpful, but are schizophrenia is which services are best suited to still being evaluated provide care for patients (Box 6). Health policy

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Memory clinics have become established as a with first-generation agents (Keefe 1999), although response to an increased demand for dementia their effect falls far short of restoring full cognitive assessment and care. Such clinics do not adhere function (Keefe 2004; Harvey 2005). Several meta- to a single type of service model or delivery, but analyses of drug treatment in schizophrenia have they have features in common: they are usually suggested that second-generation antipsychotics for people with mild to moderate dementia; a can significantly improve cognition at first, thorough assessment is conducted; diagnoses are but subsequent improvements with long-term made; and pharmacological treatment may be treatment are usually modest (Keefe 1999). There initiated and monitored. Although it is possible is only limited evidence that long-term treatment to evaluate cases of dementia in schizophrenia in can prevent the development of dementia in these clinics, an already overburdened service may schizophrenia, nor do antipsychotics appear not be able to meet all the demands of patients significantly helpful in its management. with such complex needs. Where dementia services are provided across the age range, they Acetylcholinesterase inhibitors should construct themselves to be acceptable Some evidence suggests that alterations in the and to meet the needs of people with early-onset central cholinergic system seen in people with dementia and their carers as well as those with schizophrenia, such as reduced numbers of dementia in old age (Willis 2009). Services that muscarinic and nicotinic receptors in the cortex are designed to treat people with dementia need to and , may contribute to the cognitive develop strategies to care for those with subjective deficits seen in the disorder (Friedman 2004). memory impairment but no objective deficits. The acetylcholinesterase inhibitors , People with comorbid schizophrenia and and are effective in dementia may need specific management of their dementia, especially mild to moderate Alzheimer’s psychosis. It may be argued that general adult disease (Holden 2002; Raina 2008). However, mental health services are better equipped to deal trials using these for cognitive with schizophrenia, whereas old age mental health enhancement in schizophrenia have shown mixed services have expertise in dementia. General adult results (Stip 2007; Buchanan 2008). and old age mental health services may need to Few studies have described the use of acetyl­ cooperate to provide a service that meets all the cholinesterase inhibitors in dementia associated needs of these patients. Both services should be with schizophrenia. In one, the possible beneficial able to advise people on healthy living (Box 7). effect of donepezil augmentation for the manage­ ment of comorbid schizophrenia and dementia Drug treatment was studied by Stryjer et al (2003). Six people with chronic schizophrenia and comorbid Anti­psychotics dementia received donepezil (5 mg/day) in Pharmacological management of schizophrenia single-blind fashion as augmentation to their has been available for many decades, and anti­ standard anti­psychotic for a 4-week psychotics remain the mainstay of the treatment of period. A significant improvement was noted in schizophrenia in the elderly population. However, MMSE scores and Clinical Global Impression attempts to find out whether these treatments (CGI) scores. In addition, three participants improve cognitive function in people with schizo­ demonstrated improvement on the PANSS. The phrenia have shown mixed results. authors concluded that donepezil appears to be The second-generation (atypical) antipsychotics an effective treatment for the management of may enhance memory and attention compared symptoms of dementia in people with comorbid schizophrenia and dementia. In another study, 13 people with comorbid Box 7 Healthy living chronic schizophrenia and dementia received augmentative open-label oral rivastigmine • People with schizophrenia often have poor physical (9 mg/day) for 12 weeks (Mendelsohn 2004). health associated with unhealthy lifestyles Improvements were recorded in aspects of • People with schizophrenia with or without dementia cognitive function, activities of daily living and should be encouraged to live healthily overall psychotic features. • Weight control, blood pressure control, good diet, Both of these studies involved small samples , not and avoiding may of patients and were open-label trials, and they reduce the risk of developing dementia require replication using larger, randomised double-blind designs.

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Summary Box 8 Prognosis It is difficult to suggest a particular medication for patients with comorbid chronic schizophrenia and • Dementia shortens life more than schizophrenia dementia on the basis of current evidence. • The median survival for people with dementia is 3–9 years, and it decreases significantly with age

Prognosis of dementia in schizophrenia • It is clear that Kraepelin’s gloomy prognosis for the Dementia shortens the lifespan. At any given age, cognition of people with schizophrenia is not always the case – although for some people it is people who have dementia are two to four times more likely to die than those who do not have the disease (Dewey 2001; Guehne 2006). The median survival time of people with dementia has been Another underresearched area is how best investigated in cohort studies and case series in to manage dementia in schizophrenia. Healthy various settings, and it ranges from 3 to 9 years lifestyles are clearly desirable, but as yet there (Dewey 2001; Xie 2008). However, longitudinal is little hard evidence of any benefit for people comparisons of the course of cognitive and with schizophrenia or with dementia, let alone functional decline have been very few in the with both. Acetyl­cholinesterase inhibitors look subpopulation with dementia in schizophrenia. promising as an augmentative treatment and there Mayer (1921) found that many of Kraepelin’s are many more antidementia medications under patients with paraphrenic psychoses showed development. unequivocal signs of dementia later in the course As populations across the world age, so does the of illness. Holden (1987) observed that people with population of people with schizophrenia. Age is late paraphrenia had significantly worse outcomes the biggest for dementia, and since over when they developed dementia. 20% of the general population of over-80-year-olds As mentioned earlier, Goldberg et al (1993) have dementia (Department of Health 2001), the stated that schizo­phrenia can be regarded as a proportion is likely to be higher among those with static encephalopathy. Some studies suggest that schizophrenia. We need to push the needs of this the progressive cognitive decline experienced group up the health agenda and develop more and by people with poor-outcome (long-term better services to meet them. institutionalised) schizophrenia is not a linear process across the lifespan, and the rate of decline References may accelerate after the age of 65 (Friedman 2001). Aleman A, Hijiman R, De Haan EHF, et al (1999) Memory impairment Again, more studies are needed, on both the in schizophrenia: a meta-analysis. American Journal of Psychiatry 156: survival rates and prognosis of people with 1358–66. schizophrenia once they develop dementia (Box 8). Bokat CE, Goldberg TE (2003) Letter and category fluency in schizophrenic patients: a meta-analysis. Schizophrenia Research 64: 73–8. The future Bora E, Yucel M, Pantelis C (2010) Cognitive impairment in schizophrenia and affective psychoses: implications for DSM-V criteria and beyond. The lack of evidence-based knowledge in the area 36: 36–42. of dementia in schizophrenia is highly evident. In Bowie CR, Harvey PD, Moriarty PJ, et al (2002) Cognitive assessment particular, it is not yet clear whether there is an of geriatric schizophrenic patients with severe impairment. Archives of Clinical 17: 611–23. excess of dementia in schizophrenia, be it of early Brazzelli M, Capitani E, Della Sala S, et al (1994) A neuropsychological or late onset. A sustained cognitive impairment instrument adding to the description of patients with suspected cortical suggesting a diagnosis of dementia does not dementia: the Milan overall dementia assessment. Journal of , always occur, but Kraepelin’s concept of dementia and Psychiatry 57: 1510–7. praecox appears to be right at least some of the Brodaty H, Sachdev P, Koschera A, et al (2003) Long-term outcome of late- time. It is debatable whether we under- or over­ onset schizophrenia: 5-year follow-up study. British Journal of Psychiatry 183: 213–9. diagnose dementia in this group of patients. Buchanan RW, Conley RR, Dickinson D, et al (2008) Galantamine for We need naturalistic studies to investigate this. the treatment of cognitive impairments in people with schizophrenia. Research needs to concentrate on accurately American Journal of Psychiatry 165: 82–9. diagnosing dementia in schizophrenia using the Ciompi L (1980) Catamnestic long-term study on the course of life and best neuropsychological methods available, in aging of schizophrenics. Schizophrenia Bulletin 6: 606–18. combination with brain imaging and post-mortem Cordery R, Harvey R, Frost C, et al (2002) National survey to assess examination. As we learn more about the current practices in the diagnosis and management of young people with dementia. International Journal of 17: 124–7. of schizophrenia and the subtypes of dementia, Davidson M, Harvey PD, Powchik P, et al (1995) Severity of symptoms a complicated but better understood picture will in chronically institutionalized geriatric schizophrenic patients. American emerge. Journal of Psychiatry 152: 197–207.

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MCQs c the MATRICS battery 5 As regards the diagnosis of dementia in Select the single best option for each question stem d the ACE-R schizophrenia: e the ADAS-L Cog. a cognitive impairment always means that 1 As regards schizophrenia: dementia is present a cognitive impairment is a feature of 3 Radiological signs specific in diagnosing b the presence of dementia in schizophrenia schizophrenia dementia in schizophrenia include: usually means that post-mortem examination b cognitive impairment is a criterion used to a hippocampal atrophy will reveal Alzheimer’s disease pathology diagnose schizophrenia in DSM-IV and ICD-10 b ventricular enlargement c functional imaging shows a clear diagnostic c cognitive impairment always progresses in c white matter lesions pattern schizophrenia d atrophy d the diagnosis can be made only after a history d Alzheimer’s disease invariably develops in older e none of the above. of cognitive and functional decline has been people with schizophrenia identified e dementia in schizophrenia is accepted as a 4 Of the following, the least useful in e the diagnosis should only be made by an old separate nosological entity. improving cognition in comorbid dementia age psychiatrist. and schizophrenia is to be: 2 Of the following, the least useful scale a first-generation antipsychotics for the diagnosis of dementia with b second-generation antipsychotics schizophrenia is: c galantamine a the MMSE d rivastigmine b the CERAD neuropsychological battery e donepezil.

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