Will the Real Pseudodementia Please Stand Up?

“Your reality, sir, is lies and balderdash and I'm delighted to say that I have no grasp of it whatsoever” Baron Munchausen

By Ron Keren, MD, FRCPC

seudodementia is a term that versible which resolved underscored the risk of misdiag- Phas been widely adopted in with treatment and time. Kiloh nosing dementia in individuals clinical practice, yet vastly mis- asserted that endogenous depres- with a potentially reversible disor- understood. As its name suggests, sion was the most frequent cause der. However, over time, it pseudodementia infers a “func- of pseudodementia and cautioned became apparent that all the so- tional artifact” rather than a “true against misdiagnosing it as irre- called reversible , espe- dementia” that is based on neu- versible dementia. He argued that cially the “pseudodementia of ropathological . Wernicke1 pseudodementia should be used ,” were much less first coined the term in the 1880s as a descriptive term and not a prevalent than previously thought. to describe “chronic hysterical diagnosis. In 1979, Wells,4 while A meta-analysis of 39 studies states mimicking mental weak- reporting 10 patients with psy- from 1987 to 20027 identified ness.” It was not widely used chiatric disorders as examples of potentially reversible dementias until it was reintroduced by pseudodementia, was the first to in 9% of patients but only 0.6% Madden2 in 1952 to describe refer to pseudodementia as a actually reversed and only 0.31% patients with signs and symp- diagnosis. In 1981, Caine pro- toms of dementia that disap- posed diagnostic criteria for Table 1 peared with successful treatment pseudodementia (Table 1). Proposed Diagnostic of an underlying psychotic ill- With an increasing awareness Criteria for Pseudodementia 3 ness. In 1961 Kiloh described of cognitive changes in late-life 1. Intellectual impairment in a 10 cases that mimicked irre- depression, the concept of pseu- patient with a primary dodementia was further narrowed psychiatric disorder to describe cognitive impairment 2. Features of impairment are similar to those seen in central Ron Keren, MD, FRCPC, caused by depression, commonly nervous system disorders Clinical Director, in the elderly, that mimics demen- 3. The cognitive deficits are University Health Network and tia and resolves when the depres- reversible Whitby Centre sion is successfully treated. 4. There is no known Memory Clinics neurological condition to Physician Leader, Toronto Estimates on the prevalence of account for the presentation Rehabilitation Institute, pseudodementia as it relates to Psycho-geriatric Service Caine ED. Arch Gen 1981; depression were reported to be 38(12):1359-64. Toronto, Ontario between 10% and 20%.5,6 This

The Canadian Review of Alzheimer’s Disease and Other Dementias • 11 AD and Concomitant Conditions

fully reversed. Better and longer independent risk factor and it may difficulties in making decisions, agi- follow-up in studies of patients also be the result of brain abnor- tation, irritability and changes in presenting with depression and malities in patients with AD. sleep and appetite are common in cognitive impairment was thought Caregivers have been shown to patients with dementia, independent of whether or not they are Loss of interest/apathy, loss of confidence, difficulties depressed. Therefore, diagnosing in making decisions, agitation, irritability and changes depression in individuals with in sleep and appetite are common in patients with dementia based on these criteria alone would likely lead to an over- dementia, independent of whether or not they are estimation on the prevalence of depressed. depression in dementia. A number of different sets of diagnostic criteria to be the primary reason for this over-report depression in patients for depressive syndromes have been dramatic shift in the prevalence of with AD8 and, lastly, numerous used to estimate the prevalence of reversible dementias. diagnostic criteria for depression depression in AD. Depending on the in dementia have been utilized symptoms included in the diagnos- The Association Between with poor agreement between tic criteria, the number of patients Depression and Dementia them. Hence, it is not surprising identified with depression in the The relationship between depres- that estimates of the prevalence of same cohort of patients can be high- sion and dementia is complicated depression in AD are highly vari- ly variable, and there is a low rate of for many reasons. The two syn- able, ranging from 0%9 to 87%.10 agreement between the various dromes have significant sympto- diagnostic criteria, that is, different matic overlap, cognitive impair- Symptom Overlap patients are identified by different ment is common in late-life Many of the symptoms listed in the criteria. For example, in the same depression, and depression is a DSM-IV criteria for major depres- patient cohort, the prevalence of common neuropsychiatric feature sion are frequently seen in patients depression using ICD-10 criteria of dementia. Depression may con- with dementia (Table 2). Loss of was 4.9%. It was 27.4% when using tribute to the etiology of AD as an interest/apathy, loss of confidence, the proposed diagnostic criteria for depression in AD and 43.7% when

Table 2 using the screening question from DSM-IV Diagnostic Criteria: the Neuropsychiatric Inventory Neuropsychiatric Features of Dementia (NPI). The inclusion of irritability

1. Depressed mood or loss of interest (apathy) alone as a symptom of depression 2. Poor concentration/indecisiveness (poor memory and impaired significantly increases the preva- judgement) lence of depression in AD.11 3. Decreased energy (lack of initiation, avolition) 4. Changes in sleep (impairments in diurnal sleep patterns) Is Depression a Risk Factor 5. Changes in appetite (weight loss/gain) or a Prodrome? 6. (aberrant motor activity) Is depression a cause or an effect Symptoms need to coexist in the same two-week period and not be due to a of dementia? Depression as an general medical condition independent risk factor for AD is Adapted from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). debatable. It is difficult to know whether depression in itself con-

12 • The Canadian Review of Alzheimer’s Disease and Other Dementias Pseudodementia

tributes pathophysiologically to misperceptions regarding the poten- ria for “Cogniform Disorder” and the development of AD, whether tial reversibility of dementia in eld- “Cogniform Condition.” They it is a prodrome of AD, or both. erly patients with depression, it is claim that excessive symptomatol- Prospective follow-up of elderly increasingly apparent that the con- ogy involving cognitive complaints patients presenting with cognitive cept of depressive pseudodementia, is a pervasive problem that has impairment to a memory disor- as a common cause of reversible been extensively documented in ders clinic showed that many of dementia, should be abandoned. peer-reviewed neuropsychological these patients had symptoms of journals. Cognitive symptoms can depression. When followed over A Return to Wernicke be produced or exaggerated in an time, most of them developed and the Concept of intentional, voluntary manner for AD12 despite successful treatment Conversion Pseudodementia an external incentive as in malin- of their depression and initial In examining the evolution of pseu- gering, to adopt a “sick role” as in improvements in cognition. Also, dodementia, one has to wonder , or unintention- depression, similar to other med- whether Wernicke was correct in ally, as in . As ical conditions, such as renal or conceptualizing this condition in opposed to conversion disorder and cardiac disease, may bring for- terms of a conversion disorder. , where the feigned or ward the expression of dementia Traditionally, conversion disorders exaggerated symptoms are either in patients with AD pathology. have been used to describe the completely unconscious (conver- The more distant the depres- unconscious conversion of anxiety sion disorder) or completely con- sive episode is from the onset of into physical symptoms. Little has scious (malingering), the authors dementia, the more likely that it is a contributor to the cause of the The more distant the depressive episode is from the dementia as opposed to being a onset of dementia, the more likely that it is a prodrome or part of the dementia contributor to the cause of the dementia as opposed to syndrome. Taking this into con- sideration, a systematic evidence being a prodrome or part of the dementia syndrome. review concluded that a history of depression is likely an independ- been written about the potential of argue against the dichotomous ent risk factor for dementia in gen- converting anxiety into cognitive approach of the DSM-IV for a con- eral, and for AD specifically.13 This symptoms. In a case series, tinuum, from completely uncon- concept is supported by the gluco- Hepple15 described 10 older indi- scious at one end of the spectrum, corticoid cascade hypothesis which viduals with “conversion pseudo- to partial and then full conscious- postulates that prolonged adrenal dementia.” He reported that the ness at the other end, whether or glucocorticoid secretion in patients core features of this disorder are: not in the presence of an external with depression has toxic effects on apparent cognitive impairment, incentive (e.g., litigation, disability) the hippocampus,14 leading to hip- regression and increasing physical or an adoption of the “sick role” pocampal atrophy, which is also an dependency beginning in late- (factitious disorder). The terms dis- early hallmark of AD. middle or early-old age, without order and condition differentiate The debate on depression as an evidence for an organic dementia the degree to which the individual independent risk factor is unre- from investigations or from taking exhibits cognitive dysfunction in solved, however, given the complex- into account the course of the ill- widespread areas of everyday life. ities in the relationships between ness. More recently, Delis and It is likely that cases of exagger- depression and dementia and the Wetter16 proposed diagnostic crite- ated cognitive symptoms are under-

The Canadian Review of Alzheimer’s Disease and Other Dementias • 13 AD and Concomitant Conditions

reported as it is challenging for Conclusion In today’s era of disease- physicians to make judgments In summary, depressive pseudo- modifying clinical drug trials for about their patients as possibly dementia evolved from a con- AD, mild depressive symptoms in exaggerating their symptoms, cern about the improper label- patients with dementia should not whether intentionally or uninten- ing of elderly patients with delay their diagnosis nor should it tionally. They are unlikely to know depression as having irre- exclude them from participating in whether an external incentive is versible dementia. Recent data AD research. present or whether the patient has on the prevalence of reversible Lastly, cases of feigned or exag- adopted a “sick role.” Furthermore, dementia has shown that this gerated cognitive complaints or few patients assessed for cognitive condition is extremely rare. symptoms are likely underappreciat- impairment undergo rigorous neu- Subsequently, depression is less ed. Clinicians should be urged to ropsychological evaluations with often an imitator of dementia consider this as a possibility when validity testing, and even if they do, than a predictor of dementia or a assessing patients whose cognitive today’s patients have a wealth of symptom of dementia. Treating complaints or symptoms are not information at their disposal from depression remains important. substantiated by the clinical inter- the internet, media, or coaching While it may not cure the cogni- view or cognitive assessment, espe- from experienced litigation lawyers tive disorder or reverse the cially when reinforced by an exter- which may fool even the experi- dementia, it will likely improve nal incentive or the adoption of a enced examiner. the patient’s quality of life. “sick role.”

References: Updated Meta-analysis. Arch Intern Med Psychiatry 2006; 14(7):589-97. 1. Berrios GE. Depressive pseudodementia 2003; 163(18):2219. 12. Visser PJ, Verhey FR, Ponds RW, et al, or melancholic dementia: A 19th centu- 8. Burke WJ, Roccaforte WH, Wengel SP, Distinction Between Peclinical AD and ry view. J Neurol Neurosurg Psychiatry et al. Disagreement in the Reporting of Depression. J Am Geriatr Soc 2000; 1985;48(5): 393-400. Depressive Symptoms Between Patients 48(5):479-84. 2. Madden JJ, Luhanet JA, Kaplan LA, et al. With Dementia of the Alzheimer Type 13. Jorm AF. History of depression as a risk Non-dementng psychoses in older per- and their Collateral Sources. Am J factor for dementia: an updated review. sons. JAMA 1952; 150: 1567-70. Geriatr Psychiatry 1998; 6(4):308-19. Aust N Z J Psychiatry 2001; 35(6):776-81. 3. Kiloh, LG. Pseudo-dementia. Acta 9. Knesevich JW, Martin RL, Berg L, et al. 14. Sapolsky RM, Krey LC, McEwen BS. The Psychiatrica Scandinavica 1961; Preliminary report on affective symp- neuroendocrinolgy of and aging: 37:336-51 toms in early stages of senile dementia the glucorticoid cascade hypothesis. 4. Wells C. Pseudodementia. Am J of the Alzheimer type. Am J Psychiatry Endocr Rev 1986; 7(3):284-301. Psychiatry 1979; 136(7):895-900. 1983; 140(2):233-5. 15. Hepple J. Conversion pseudodementia 5. Garcia CA, Reding MJ, Blass JP, et al. 10. Merriam AE, Aronson MK, Gaston P, et in older people: a descriptive case Overdiagnosis of dementia. J Am Geriatr al: The psychiatric symptoms of series. Int J Geriatr Psychiatry 2004; Soc 1981; 29(9):407-10. Alzheimer’s disease. J Am Geriatr Soc 19(10):961-7. 6. Jeste, DV et al. Pseudodementia: Myths 1988; 36(1):7-12. 16. Delis DC, Wetter SR. Cogniform disor- and realities. Psychiatric Annals 1990; 11. Vilalta-Franch J, Garre-Olmo J, López- der and Cogniform condition: Proposed 20:71-9. Pousa S, et al. Comparison of different diagnoses for excessive cognitive symp- 7. Clarfield AM. The Decreasing clinical diagnostic citeria for depression toms. Arch Clin Neuropsychol 2007; Prevalence of Reversible Dementias: An in Alzheimer’s disease, Am J Geriatr 22(5):589-604.

14 • The Canadian Review of Alzheimer’s Disease and Other Dementias