Cases That Test Your Skills

Delusions, hypersexuality, and a steep cognitive decline Awais Aftab, MD, and Philipp L. Dines, MD, PhD

Ms. P, age 56, is acting bizarre. When her symptoms appeared How would you 10 years ago, she was a senior accountant, but was fired when handle this case? Answer the challenge her work deteriorated. What could account for her decline? questions throughout this article

CASE Inconsistent stories cessible because she refuses to allow her Ms. P, age 56, is an Asian American woman chart to be released. who was brought in by police after being Ms. P has not taken the psychiatric medi- found standing by her car in the middle of cations prescribed for her for several months; a busy road displaying bizarre behavior. She she says, “I don’t need medication. I am self- provides an inconsistent story about why she healing.” She denies using illicit substances, was brought to the hospital, saying that the including marijuana, smoking, and current police did so because she wasn’t driving fast alcohol use, but reports occasional social enough and because her English is weak. At drinking in the past. Her urine drug screen is another point, she says that she had stopped negative. her car to pick up a penny from the road and The most striking revelation in Ms. P’s the police brought her to the hospital “to social history is her high premorbid func- experience life, to rest, to meet people.” tional status. She has 2 master’s degrees and Upon further questioning, Ms. P reveals had been working as a senior accountant at that she is experiencing racing thoughts, a major hospital system until 7 years ago. In feels full of energy, has pressured speech, contrast, when interviewed at the hospital, and does not need much sleep. She also is Ms. P reports that she is working at a child sexually preoccupied, talks about having care center. extra-marital affairs, and expresses her infat- On mental status exam, Ms. P is half- uation with TV news anchors. She says she is draped in a hospital gown, casual, overly sexually active but is unable to offer any fur- friendly, smiling, and twirling her hair. Her ther details, and—while giggling—asks the mood is elevated with inappropriate affect. treatment team not to reveal this informa- Her thought process is bizarre and illogical. tion to her husband. Ms. P also reports hear- She is alert, fully oriented, and her sensorium ing angels singing from the sky. is clear. She has persistent ambivalence and Chart review reveals that Ms. P had been contradictory thoughts regarding suicidal admitted to same hospital 5 years earlier, at Dr. Aftab is a Resident, and Dr. Dines is Assistant Professor and which time she was given diagnoses of late- Psychiatric Medical Director, Inpatient Neuropsychiatric Service, Department of Psychiatry, University Hospitals Case Medical onset schizophrenia (LOS) and mild cogni- Center, Case Western Reserve University, Cleveland, Ohio. tive impairment. Ms. P also had 3 psychiatric Disclosures inpatient admissions in the past 2 years at a The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturer of Current Psychiatry different hospital, but her records are inac- competing products. Vol. 15, No. 2 45 Cases That Test Your Skills

Table 1 said that, just before being fired, Ms. P had Ms. P’s differential diagnosis been reading the mystery novel The Da Vinci Code and believed that events in the book Bipolar disorder, current manic episode specifically applied to her. Ms. P would stay Schizophrenia up all night making clothes; when she would Schizoaffective disorder, bipolar type go to work, she was caught sleeping on the Major neurocognitive disorder, due to job and performing poorly, including submit- Alzheimer’s disease ting reports with incorrect information. She Major neurocognitive disorder, due to frontotemporal lobar degeneration yelled at co-workers and was unable to take Major neurocognitive disorder, unspecified direction from her supervisors. Ms. P’s husband also reported that she believed people were trying to “look like Clinical Point her,” by having plastic surgery. He reported ideation. Recent and remote memory are unusual behavior at home, including eating DSM authors largely intact. She does not express homi- food off the countertop that had been out for comment that it is not cidal ideation. hours and was not fit for consumption. yet clear whether LOS Ms. P’s husband could not be contacted is the same condition What could be causing Ms. P’s and during this admission because he was out of as schizophrenia functional decline? country and they were separated. Collateral a) major neurocognitive disorder information is obtained from Ms. P’s mother, diagnosed earlier b) schizophrenia who lives apart from her but in the same city in life c) schizoaffective disorder and speaks no English. She confirms Ms. P’s d) bipolar disorder, current manic episode high premorbid functioning, and reports that her daughter’s change in behavior went back as far as 10 years. She reports that Ms. P had HISTORY Fired from her job problems controlling anger and had frequent According to Ms. P’s chart from her admis- altercations with her husband and mother, sion 5 years earlier, police brought her to including threatening her with a knife. Self- the hospital because she was causing a dis- care and hygiene then declined strikingly. turbance at a restaurant. When interviewed, She began to have odd religious beliefs Ms. P reported a false story that she fought (eg, she was the daughter of Jesus Christ) and with her husband, kicked him, and spat on insisted on dressing in peculiar ways. his face. She said that her husband then No family history of psychiatric disorders, punched her in the face, she ran out of the such as schizophrenia, bipolar disorder, or house, and a bystander called the police. At , was reported (Table 1). the time, her husband was contacted and denied the incident. He said that Ms. P had gone to the store and not returned, and he The authors’ observations did not know what happened to her. The existence of LOS as a distinct subtype Her husband reported a steady and pro- of schizophrenia has been the subject of Discuss this article at gressive decline in function and behavior discussion and controversy as far back as www.facebook.com/ dating back to 8 years ago with no known Manfred Bleuler in 1943 who coined the CurrentPsychiatry prior behavioral disturbances. In the chart term “late-onset schizophrenia.”1 In 2000, from 5 years ago, her husband reported that a consensus statement by the International Ms. P had been a high-functioning senior Late-Onset Schizophrenia Group standard- executive accountant at a major hospital ized the nomenclature, defining LOS as system 7 years before the current admission, onset between age 40 and 60, and very-late- Current Psychiatry 46 February 2016 at which time she was fired from her job. He onset schizophrenia-like psychosis (VLOS) continued on page 48 Cases That Test Your Skills

continued from page 46

Table 2 Cognition in late-onset schizophrenia There are global deficits in LOS, as well as specific deficits in , visuospatial constructional abilities, verbal fluency, psychomotor speech, memory, attention, and working memory LOS generally is associated with relatively milder cognitive deficits and deficits in attention, fluency, global cognition, IQ, and visuospatial construction Premorbid cognitive functioning is less impaired in LOS compared with onset before age 40 Studies with follow-up of 3 to 5 years have reported increased risk of dementia with LOS, usually unspecified or of Alzheimer’s type Neuropsychological tests can help differentiate patients with LOS and patients with Alzheimer’s and frontotemporal dementia LOS: late-onset schizophrenia Clinical Point

Premorbid as onset after age 60.2 Although there is no The presence of cognitive symptoms in educational, diagnostic subcategory for LOS in DSM, LOS is less well-studied and understood occupational, DSM-5 notes that (1) women are overrepre- (Table 2). The International Consensus and psychosocial sented in late-onset cases and (2) the course Statement reported that no difference in functioning are less generally is characterized by a predominance type of cognitive deficit has been found in of psychotic symptoms with preservation of early–onset cases (onset before age 40) com- impaired in LOS affect and social functioning.3 DSM authors pared with late-onset cases, although LOS comment that it is not yet clear whether LOS is associated with relatively milder cogni- is the same condition as schizophrenia diag- tive deficits. Additionally, premorbid edu- nosed earlier in life. Approximately 23% of cational, occupational, and psychosocial schizophrenia cases have onset after age 40.4 functioning are less impaired in LOS than they are in early-onset schizophrenia.2 Cognitive symptoms in LOS Rajji et al7 performed a meta-analysis The presence of cognitive deficits in schizo- comparison of patients with youth-onset phrenia is common and well-recognized. schizophrenia, adults with first-episode The intellectual impairment is generalized schizophrenia, and those with LOS on and global, and there also is specific impair- their cognitive profiles. They reported that ment in a range of cognitive functions, such patients with youth-onset schizophrenia as executive functions, memory, psycho­ have globally severe cognitive deficits, motor speed, attention, and social cogni- whereas those with LOS demonstrate mini- tion.5 Typically these cognitive impairments mal deficits on arithmetic, digit symbol are present before onset of psychotic symp- coding, and vocabulary but larger deficits toms. Although cognitive symptoms are not on attention, fluency, global cognition, IQ, part of the formal diagnostic criteria, DSM-5 and visuospatial construction.7 acknowledges their presence.3 In a system- There are conflicting views in the lit- atic review on nature and course of cognitive erature with regards to the course of cogni- function in LOS, Rajji and Mulsant6 report tive deficits in schizophrenia. One group of that global deficits and specific deficits in researchers believes that there is progressive executive functions, visuospatial construc- deterioration in cognitive functioning over tional abilities, verbal fluency, and psycho- time, while another maintains that cogni- motor speech have been found consistently tive impairment in schizophrenia is largely in studies of LOS, although the presence of “a static encephalopathy” with no signifi- deficits in memory, attention, and working cant progression of symptoms.8 A number of Current Psychiatry 48 February 2016 memory has been less consistent. studies referenced by Rajji and Mulsant6 in Cases That Test Your Skills

their systematic review report Figure that cognitive deficits seen Ms. P’s visuospatial executive dysfunction in patients with LOS largely on clock drawing and cube copying tests are stable on follow-up with an average duration of up to 3 years. However, 2 studies with longer follow-up report evidence of cognitive decline.9,10

Relevant findings from the literature. Brodaty et al9 fol- lowed 27 patients with LOS without dementia and 34 oth- Clinical Point erwise healthy participants at baseline, 1 year, and 5 years. Findings from the They reported that 9 patients literature suggest with LOS and none of the con- that dementia in trol group were found to have dementia Vocabulary, Information, Digit Span, and LOS and VLOS is (5 Alzheimer type, 1 vascular, and 3 dementia Comprehension subtests, and the Hooper of different basis of unknown type) at 5-year follow-up. Some Visual Organization test can differentiate than Alzheimer’s patients had no clinical signs of dementia LOS and frontotemporal dementia.12 at baseline or at 1-year follow-up, but were dementia found to have dementia at 5-year follow-up. The authors speculated that LOS might be a EVALUATION Significant impairment prodrome of Alzheimer-type dementia. CT head and MRI brain scans without con- Kørner et al10 studied 12,600 patients trast suggest mild generalized atrophy that is with LOS and 7,700 with VLOS, selected more prominent in frontal and parietal areas, from the Danish nationwide registry; fol- but the scans are otherwise unremarkable low-up was 3 to 4.58 years. They concluded overall. A PET scan is significant for hypoac- that patients with LOS and VLOS were tivity in the temporal and parietal lobes but, at 2 to 3 times greater risk of developing again, the images are interpreted as unre- dementia than patients with osteoarthritis markable overall. or the general population. The most com- Ms. P scores 21 on the Montreal Cognitive mon diagnosis among patients with schizo- Assessment (MoCA), indicative of significant phrenia was unspecified dementia, with cognitive impairment (normal score, ≥26). Alzheimer’s dementia (AD) being the most This is a 3-point decline on a MoCA per- common diagnosis in control groups. The formed during her admission 5 years earlier. findings suggest that dementia in LOS and Ms. P scores 8 on the Middlesex Elderly VLOS has a different basis than AD. Assessment of Mental State, the lowest score Zakzanis et al11 investigated which neuro- in the borderline range of cognitive function psychological tests best differentiate patients for geriatric patients. She scores 13 on the with LOS and those with AD or frontotem- Kohlman Evaluation of Living Skills, indicat- poral dementia. They reported that Wechsler ing that she needs maximal supervision, Adult Intelligence Scale-Revised (WAIS-R) structure, and support to live in the commu- Similarities subtest and the California Verbal nity. Particularly notable is that Ms. P failed Learning Test (both short- and long-delay 5 out of 6 subtests in money management— free recall) can differentiate LOS from AD, a marked decline for someone who had Current Psychiatry and a test battery comprising the WAIS-R worked as a senior accountant. Vol. 15, No. 2 49 continued Cases That Test Your Skills

Table 3 DSM-5 diagnostic criteria for major neurocognitive disorder A. Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or ) based on: 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 B. The cognitive deficits interfere with independence in everyday activities (ie, at a minimum, requiring assistance with complex instrumental activities of daily living such as paying bills or managing medications) C. The cognitive deficits do not occur exclusively in the context of a D. The cognitive deficits are not better explained by another (eg, major depressive Clinical Point disorder, schizophrenia) Source: Reference 3 Late-onset schizoaffective disorder might Given Ms. P’s significant cognitive decline fective disorder (n = 29), schizophrenia represent a variant from premorbid functioning, verified by col- (n = 154), or nonpsychotic mood disor- of LOS but with lateral information, and current cognitive der (n = 27) and concluded that late-onset deficits established on standardized tests, schizoaffective disorder might represent a additional mood we determine that, in addition to a diagnosis variant of LOS in clinical symptom profiles symptoms of schizoaffective disorder, she might meet and cognitive impairment but with addi- DSM-5 criteria for unspecified major neuro- tional mood symptoms.16 cognitive disorder if her functioning does not improve with treatment. How would you begin treating Ms. P? a) start a mood stabilizer b) start an atypical The authors’ observations c) obtain more history and collateral There is scant literature on late-onset information schizoaffective disorder. Webster and d) recommend outpatient treatment Grossberg13 conducted a retrospective chart review of 1,730 patients age >65 who were admitted to a geriatric psychiatry unit The authors’ observations from 1988 to 1995. Of these patients, 166 Given Ms. P’s manic symptoms, thought (approximately 10%) were found to have disorder, and history of psychotic symp- late life-onset psychosis. The psychosis was toms with diagnosis of LOS, we assigned attributed to various causes, such as demen- her a presumptive diagnosis of schizoaf- tia, depression, bipolar disorder, medical fective disorder, bipolar type. From the causes, delirium, medication toxicity. Two patient report, collateral information from patients were diagnosed with schizophre- her mother, earlier documented collateral nia and 2 were diagnosed with schizoaffec- from her husband, and chart review, it was tive disorder (the authors did not provide apparent to us that Ms. P’s psychiatric his- additional information about the patients tory went back only 10 years—therefore with schizoaffective disorder). Brenner meeting temporal criteria for LOS. et al14 reports a case of late-onset schizoaf- Clinical assessment (Figure, page 49) and fective disorder in a 70-year-old female standardized tests revealed the presence of patient. Evans et al15 compared outpatients neurocognitive deficits sufficient to meet Current Psychiatry 50 February 2016 age 45 to 77 with a diagnosis of schizoaf- criteria for major neurocognitive disorder Cases That Test Your Skills

(Table 33). The pattern of neurocognitive defi- cits is consistent with an AD-like amnestic Related Resources picture, although no clear-cut diagnosis was • Goff DC, Hill M, Barch D. The treatment of cognitive impairment in schizophrenia. Pharmacol Biochem Behav. present, and the neurocognitive disorder 2011;99(2):245-253. was better classified as unspecified rather • Radhakrishnan R, Butler R, Head L. Dementia in schizophrenia. than of a particular type. It remains uncer- Adv Psychiatr Treat. 2012;18(2):144-153. tain whether cognitive deficits of severity Drug Brand Names that meet criteria for major neurocognitive Aripiprazole • Abilify Mematine • Namenda Divalproex sodium • Depakote disorder are sufficiently accounted for by the diagnosis of LOS alone. Unless diagnos- tic criteria for schizophrenia are expanded to include cognitive deficits, a separate poor insight and judgment. She demonstrates diagnosis of major neurocognitive disorder severe ambivalence in all matters, consistently Clinical Point is warranted at present. gives inconsistent accounts of the past, and makes dramatic false statements. It was apparent For example, when asked about her to us that Ms. P’s TREATMENT Pharmacotherapy children, Ms. P tells us that she has 6 chil- psychiatric history On the unit, Ms. P is observed by nurs- dren—the youngest 3 months old, at home went back only ing staff wandering, with some pressured by himself and “probably dead by now.” In 10 years—therefore speech but no behavioral agitation. Her reality, she has only a 20-year-old son who clothing had been bizarre, with multiple is studying abroad. Talking about her mar- meeting temporal layers, and, at one point, she walks with her riage, Ms. P says she and her husband are criteria for LOS gown open and without undergarments. not divorced on paper but that, because they She also reports to the nurses that she has haven’t had sex for 8 years, the law has pro- a lot of sexual thoughts. When the inter- vided them with an automatic divorce. view team enters her room, they find her masturbating. Ms. P is started on aripiprazole, 10 mg/d, OUTCOME Significant improvement titrated to 20 mg/d, and divalproex sodium, Ms. P shows significant response to aripipra- 500 mg/d. The decision to initiate a cognitive zole and divalproex, which are well tolerated enhancer, such as an acetylcholinesterase without significant adverse effects. Her limi- inhibitor or memantine, is deferred to out- tations in executive functioning and rational patient care to allow for the possibility that thought process lead the treatment team her cognitive features will improve after the to consider nursing home placement under psychosis is treated. guardianship. Days before discharge, how- By the end of first week, Ms. P’s manic ever, reexamination of her neuropsychiatric features are no longer prominent but her state suggests significant improvement in thought process continues to be bizarre, with thought process, with improvement in cogni-

Bottom Line Global as well as specific cognitive deficits are associated with late-onset schizophrenia. Studies have reported increased risk of dementia in these patients over the course of 3 to 5 years, usually unspecified or Alzheimer’s type. It is imperative to assess patients with schizophrenia, especially those age ≥40, for Current Psychiatry presence of neurocognitive disorder by means of neurocognitive testing. Vol. 15, No. 2 51 Cases That Test Your Skills

tive features. Ms. P also becomes cooperative cognition in schizophrenia: meta-analysis. Br J Psychiatry. 2009;195(4):286-293. with treatment planning. 8. Goldberg TE, Hyde TM, Kleinman JE, et al. Course of schizophrenia: neuropsychological evidence for a static The treatment team has meetings with encephalopathy. Schizophr Bull. 1993;19(4):797-804. Ms. P’s mother to discuss monitoring and 9. Brodaty H, Sachdev P, Koschera A, et al. Long-term outcome of late-onset schizophrenia: 5-year follow-up study. Br J plans for discharge. Ms. P is discharged with Psychiatry. 2003;183(3):213-219. follow-up arranged at community mental 10. Kørner A, Lopez AG, Lauritzen L, et al. Late and very-late first‐contact schizophrenia and the risk of dementia—a health services. nationwide register based study. Int J Geriatr Psychiatry. 2009;24(1):61-67. 11. Zakzanis KK, Andrikopoulos J, Young DA, et al. References Neuropsychological differentiation of late-onset 1. Bleuler M. Die spätschizophrenen Krankheitsbilder. schizophrenia and dementia of the Alzheimer’s type. Appl Fortschr Neurol Psychiatr. 1943;15:259-290. Neuropsychol. 2003;10(2):105-114. 2. Howard R, Rabins PV, Seeman MV, et al. Late-onset 12. Zakzanis KK, Kielar A, Young DA, et al. Neuropsychological schizophrenia and very-late-onset schizophrenia-like differentiation of late onset schizophrenia and psychosis: an international consensus. The International frontotemporal dementia. Cognitive Neuropsychiatry. 2001; Clinical Point Late-Onset Schizophrenia Group. Am J Psychiatry. 2000; 6(1):63-77. 157(2):172-178. 13. Webster J, Grossberg GT. Late-life onset of psychotic Unless criteria for 3. Diagnostic and statistical manual of mental disorders, 5th ed. symptoms. Am J Geriatr Psychiatry. 1998;6(3):196-202. Washington, DC: American Psychiatric Association; 2013. 14. Brenner R, Campbell K, Konakondla K, et al. Late schizophrenia are 4. Harris MJ, Jeste DV. Late-onset schizophrenia: an overview. onset schizoaffective disorder. Consultant. 2014;53(6): Schizophr Bull. 1988;14(1):39-55. 487-488. expanded to include 5. Tandon R, Keshavan MS, Nasrallah HA. Schizophrenia, 15. Evans JD, Heaton RK, Paulsen JS, et al. Schizoaffective “just the facts”: what we know in 2008 part 1: overview. disorder: a form of schizophrenia or affective disorder? cognitive deficits, a Schizophr Res. 2008;100(1):4-19. J Clin Psychiatry. 1999;60(12):874-882. 6. Rajji TK, Mulsant BH. Nature and course of cognitive 16. Jeste DV, Blazer DG, First M. Aging-related diagnostic separate diagnosis of function in late-life schizophrenia: a systematic review. variations: need for diagnostic criteria appropriate for major neurocognitive Schizophr Res. 2008;102(1-3):122-140. elderly psychiatric patients. Biol Psychiatry. 2005;58(4): 7. Rajji TK, Ismail Z, Mulsant BH. Age at onset and 265-271. disorder is warranted

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