GUEST EDITORIALS. Psychosis of Alzheimer s Disease and Related Dementias. Diagnostic Criteria for a Distinct Syndrome

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1 GUEST EDITORIALS Psychosis of Alzheimer s Disease and Related Dementias Diagnostic Criteria for a Distinct Syndrome Dilip V. Jeste, M.D. Sanford I. Finkel, M.D. Copyright 2000 American Association for Geriatric Psychiatry T he very first patient with dementia described by Alzheimer 1 had psychotic symptoms, including paranoid delusions and hallucinations. Subsequently, the term senile psychosis was commonly used in the older literature to refer to psychosis in elderly patients with dementia. Numerous studies of the prevalence and nature of psychotic symptoms have been conducted in patients with Alzheimer s disease (AD) and other dementias. Although some of this literature is limited by methodologic problems such as small sample sizes, variable assessment instruments, and inclusion of mixed categories of dementia, methodologically more rigorous investigations have generally reported a frequency of psychotic symptoms in AD to be between 30% and 50%. 2 6 In a recent study of 329 patients with AD, Paulsen et al. 7 computed the cumulative 4- year incidence of new-onset psychosis of AD to be 51%. Once present, delusions recur or persist for several years in a majority of AD patients. 8,9 Furthermore, a number of groups of researchers have found that delusions and hallucinations are commonly associated with aggression, agitation, and disruptive behavior in patients with AD Psychotic symptoms are a major cause of caregiver distress and often result in institutionalization of the patients The common psychotic symptoms reported in the AD patients have been delusions and hallucinations. The delusions are typically paranoid type, non-bizarre, and simple. Complex or bizarre delusions seen in patients with schizophrenia are conspicuously absent in the patients with AD. Misidentification phenomena, however, are common in AD. 17 Whereas hallucinations in AD are more frequently visual than auditory, the reverse is true for schizophrenia. Schneiderian first-rank symptoms, such as hearing multiple voices talking to one another or running a commentary on the patient s actions are extremely rare in AD patients. Although psychosis and depression may coexist in a patient with AD, active suicidal ideation is rare, whereas approximately 50% of patients with schizophrenia attempt suicide, and 10% make fatal suicidal attempts. Because a large majority of the elderly patients with schizophrenia are those with onset of illness during early adult years of life, they have a past history of psychotic episodes, and a sizable minority also have a positive family history of the disorder. In contrast, past history of psychosis is rare in AD patients. 4 The long-term course of schizophrenia is generally stable, and although complete symptomatic remission may occur in old age, it is uncommon. 18 A proportion of elderly patients with schizophrenia may develop dementia; this dementia is, however, neuropathologically different from that of AD. 19,20 In AD patients, psychotic symptoms tend to disappear in advanced stages of dementia; this could reflect an apparent rather than real remission, in that the patients with severe dementia may be unable to articulate their delusions and hallucinations. 4 Nonetheless, the overall duration of the necessary antipsychotic treatment to control and prevent relapses is much shorter in AD patients with psychosis than in those with schizophrenia. Finally, the daily Am J Geriatr Psychiatry 8:1, Winter

2 maintenance dosages of antipsychotics required for AD patients with psychosis are considerably lower than those prescribed for elderly patients with schizophrenia. 21 We believe that psychosis of AD is a distinct syndrome that is markedly different from schizophrenia in elderly patients. Table 1 summarizes the main differences between the two syndromes. Several groups of investigators have reported potentially relevant clinical, neuropsychological, and neurobiological differences between the AD patients with vs. those without psychosis. For example, Stern et al. 22 observed that among AD patients, psychosis was associated with a greater prevalence of extrapyramidal signs and a more rapid cognitive decline. Jeste et al. 4 noted that, compared with AD patients without psychosis, those with psychosis had greater impairment on putative neuropsychological tests of frontal lobe function. On the basis of neuroimaging studies, Sultzer 23 found an association between delusions in dementia and dysfunction in heteromodal association or paralimbic areas of the frontotemporal cortex. Neuropathological and neurochemical investigations by Zubenko et al. 24 found that, among patients with primary dementia, those with psychosis had increased neurodegenerative changes in the cortex (but not in the aminergic nuclei), increased subcortical norepinephrine, and reduced cortical and subcortical serotonin/5-hiaa. Mukaetova-Ladinska et al. 25 reported that AD patients with psychosis had four to five times higher levels of abnormal Paired Helical Filament (PHF)-tau protein in the entorhinal and temporal cortices than nonpsychotic AD patients. Although studies such as these have not yet established a neuropathololgical basis for psychosis in AD, they have yielded valuable TABLE 1. Comparison of psychosis of Alzheimer s disease (AD) with schizophrenia in elderly patients Psychosis in AD Schizophrenia 1. Incidence 30% 50% Less than 1% 2. Bizarre or complex Rare Frequent delusions 3. Misidentification of Frequent Rare caregivers 4. Common form of Visual Auditory hallucinations 5. Schneiderian first-rank Rare Frequent symptoms 6. Active suicidal ideation Rare Frequent 7. Past history of psychosis Rare Very common 8. Eventual remission of Frequent Uncommon psychosis 9. Need for many years of maintenance on antipsychotics Uncommon Very common 10. Average optimal daily dose of an antipsychotic 15% 25% of that in a young adult with schizophrenia 40% 60% of that in a young adult with schizophrenia 30 Am J Geriatr Psychiatry 8:1, Winter 2000

3 results for understanding the histopathological underpinnings of psychotic symptoms in patients with dementia. 26 There have been numerous treatment trials for psychosis of AD, although many have also included patients with other types of dementias (e.g., vascular dementia), as well as those with agitation in the absence of psychosis. The older studies were not very promising, in part because of methodologic shortcomings such as very short duration of a number of the trials along with high dropout rates due to side effects of the drugs used. 29 During the last 2 years, three trials have been reported of the newer atypical antipsychotics risperidone and olanzapine, conducted in nursing home patients with AD complicated by psychosis or agitation These largescale, placebo-controlled, double-blind trials found significant improvement with the antipsychotic used without an elevated risk of major side effects at the optimal dosages of the respective drugs at least over a 6- to 12-week period. This finding has increased the importance of an accurate diagnosis of psychosis of AD to practical utility beyond its theoretical implications. There have, however, been no specific criteria for diagnosing psychosis of AD as a distinct entity. The Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) 33 recommends additional coding if delusions are a predominant feature of the dementia (either of the Alzheimer type or vascular), but provides no criteria for this subcategory. For epidemiologic, clinical, and, especially, treatment studies, and for regulatory purposes, there is a critical need for defining specific diagnostic criteria for psychosis of AD in a manner analogous to that used for schizophrenia and other major psychiatric disorders in the DSM-IV. Table 2 lists our proposed criteria. The goal of these criteria is to operationally define the entity of psychotic syndrome in patients with AD that would exclude psychotic symptoms secondary to delirium only (although the two may coexist for a period), other general-medical conditions, and substance use (either drugs of abuse or medications), as well as schizophrenia and related primary psychotic disorders, such as delusional disorder and mood disorder with psychotic features. The main associated features listed, that is, agitation, negative symptoms, and depression, are not only common accompaniments of psychosis of AD, but also have important therapeutic implications. One limitation of these diagnostic criteria, as with other DSM- IV categories, is that they do not obviate a need for good clinical judgment for example, in ruling out delirium as the exclusive cause of psychotic symptoms in the early stages, or in deciding whether a patient with AD has delusions of misidentification or is confabulating to compensate for memory loss. Also, no cutoff for severity of symptoms is included. Rating scales such as the BEHAVE- AD 34 or the Neuropsychiatric Inventory 35 may be used for that purpose. Am J Geriatr Psychiatry 8:1, Winter

4 These criteria may apply to a similar psychotic syndrome associated with other dementias such as Lewy-body dementia, vascular dementia, and mixed dementia. However, in view of the relatively small number of systematic investigations of psychosis in non-ad dementias, 27,28,36 more research is recommended in these and other types of dementias. An important goal of these diagnostic criteria for psychosis of dementia is to help distinguish it from psychotic symptoms attributable to known causes. For example, the most common form of psychosis in Parkinson s disease is caused by dopaminergic drugs, and may respond rapidly to dopaminergic drug withdrawal or dose reduction. 37 It is thus etiologically different from the non-drug induced chronic psychotic syndrome described in this article. We have found the proposed criteria to have reliability and at least face validity for diagnosing psychosis of AD; nonetheless, larger field trials would be necessary to establish their construct validity as well as their interrater reliability across sites. TABLE 2. Diagnostic criteria for psychosis of Alzheimer s disease (AD) A. Characteristic Symptoms Presence of one (or more) of the following symptoms: 1. Visual or auditory hallucinations 2. Delusions B. Primary Diagnosis All the criteria for dementia of the Alzheimer type are met a C. Chronology of the onset of symptoms of psychosis vs. onset of symptoms of dementia There is evidence from the history that the symptoms in Criterion A have not been present continuously since prior to the onset of the symptoms of dementia D. Duration and Severity The symptom(s) in Criterion A have been present, at least intermittently, for 1 month or longer. Symptoms are severe enough to cause some disruption in patients and/or others functioning. E. Exclusion of schizophrenia and related psychotic disorders Criteria for Schizophrenia, Schizoaffective Disorder, Delusional Disorder, or Mood Disorder With Psychotic Features have never been met F. Relationship to delirium The disturbance does not occur exclusively during the course of a delirium G. Exclusion of other causes of psychotic symptoms The disturbance is not better accounted for by another general-medical condition or direct physiological effects of a substance (e.g., a drug of abuse, a medication) Associated features: (Specify if associated) With Agitation: when there is evidence, from history or examination, of prominent agitation with or without physical or verbal aggression With Negative Symptoms: when prominent negative symptoms, such as apathy, affective flattening, avolition, or motor retardation, are present With Depression: when prominent depressive symptoms, such as depressed mood, insomnia or hypersomnia, feelings of worthlessness or excessive or inappropriate guilt, or recurrent thoughts of death, are present a Note: For other dementias, such as vascular dementia, Criterion B will need to be modified appropriately. 32 Am J Geriatr Psychiatry 8:1, Winter 2000

5 The work was supported, in part, by National Institute for Mental Health grants MH49671, MH , and MH45131, and by the Department of Veterans Affairs. References 1. Alzheimer A: Über eine eigenartige erkrankung der hirnrinde. Allemeine Zeitschrift für Psychiatrie und Psychisch-Gerichtliche Medicin 1907; 64: Wragg R, Jeste DV: Overview of depression and psychosis in Alzheimer s disease. Am J Psychiatry 1989; 146: Mendez M, Martin R, Smyth KA, et al: Psychiatric symptoms associated with Alzheimer s disease. J Neuropsychiatry Clin Neurosci 1990; 2: Jeste DV, Wragg RE, Salmon DP, et al: Cognitive deficits of patients with Alzheimer s disease with and without delusions. Am J Psychiatry 1992; 149: Hirono N, Mori E, Yasuda M, et al: Factors associated with psychotic symptoms in Alzheimer s disease. J Neurol Neurosurg Psychiatry 1998; 64: Wragg RE, Jeste DV: Neuroleptics and alternative treatments: management of behavioral symptoms and psychosis in Alzheimer s disease and related conditions. Psychiatr Clin North Am 1988; 11: Paulsen JS, Salmon DP, Thal LJ, et al: Incidence of and risk factors for psychosis of Alzheimer s disease. Neurology 1999 (in press) 8. Levy ML, Cummings JL, Fairbanks LA, et al: Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer s disease. Am J Psychiatry 1996; 153: Devanand DP, Jacobs DM, Tang MX, et al: The course of psychopathologic features in mild-to-moderate Alzheimer s disease. Arch Gen Psychiatry 1997; 54: Rabins PV, Mace NL, Lucas MJ: The impact of dementia on the family. JAMA 1982; 248: Flynn FG, Cummings FL, Gornbein J: Delusions in dementia syndromes: investigation of behavioral and neuropsychological correlates. J Neuropsychiatry Clin Neurosci 1991; 3: Rockwell E, Jackson E, Vilke G, et al: A study of delusions in a large cohort of Alzheimer s disease patients. Am J Geriatr Psychiatry 1994; 2: Gilley DW, Wilson RS, Beckett LA, et al: Psychotic symptoms and physically aggressive behavior in Alzheimer s disease. J Am Geriatr Soc 1997; 45: Steele C, Rovner B, Chase GA, et al: Psychiatric symptoms and nursing home placement of patients with Alzheimer s disease. Am J Psychiatry 1990; 147: Magni E, Binetti G, Bianchetti A, et al: Risk of mortality and institutionalization in demented patients with delusions. J Geriatr Psychiatry Neurol 1996; 9: Stern Y, Tang M, Albert MS, et al: Predicting time to nursing home care and death in individuals with Alzheimer s disease. JAMA 1997; 277: Burns A, Jacoby R, Levy R: Psychiatric phenomena in Alzheimer s disease, I: disorders of thought content. Br J Psychiatry 1990; 157: Morris SK, Jeste DV: Schizophrenia and other psychotic disorders, in Principles of Geriatric Medicine and Gerontology, 4th Edition. Edited by Hazzard WR, Blass JP, Ettinger WH Jr, et al. New York, McGraw-Hill, 1998, pp Davidson M, Harvey P, Welsh KA, et al: Cognitive functioning in late-life schizophrenia: a comparison of elderly schizophrenic patients with Alzheimer s disease. Am J Psychiatry 1996; 153: Arnold SE, Franz BR, Trojanowski JQ: Elderly patients with schizophrenia exhibit infrequent neurodegenerative lesions. Neurobiol Aging 1994; 15: Jeste DV, Rockwell E, Harris MJ, et al: Conventional antipsychotics in elderly patients. Am J Geriatr Psychiatry 1999; 7: Stern Y, Albert M, Brandt J, et al: Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer s disease: prospective analyses from the predictors study. Neurology 1994; 44: Sultzer DL: Neuroimaging and the origin of psychiatric symptoms in dementia. Int Psychogeriatr 1996; 8 (suppl 3): Am J Geriatr Psychiatry 8:1, Winter

6 24. Zubenko GS, Moossy J, Martinez AJ, et al: Neuropathologic and neurochemical correlates of psychosis in primary dementia. Arch Neurol 1991; 48: Mukaetova-Ladinska EB, Harrington CR, Xuereb J, et al: Treating Alzheimer s and other dementias, in Treating Alzheimer s and Other Dementias. Edited by Bergener M, Finkel SI. New York, Springer, 1995, pp Bondareff W: Neuropathology of psychotic symptoms in Alzheimer s disease. Int Psychogeriatr 1996; 8 (suppl 3): Binetti G, Bianchetti A, Padovani A, et al: Delusions in Alzheimer s disease and multi-infarct dementia. Acta Neurol Scand 1993; 88: Sultzer DL, Levin HS, Mahler ME, et al: A comparison of psychiatric symptoms in vascular dementia and Alzheimer s disease. Am J Psychiatry 1993; 150: Schneider LS, Pollock VE, Lyness SA: A metaanalysis of controlled trials of neuroleptic treatment in dementia. J Am Geriatr Soc 1990; 38: Katz IR, Jeste DV, Mintzer JE, et al: Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trail. J Clin Psychiatry 1999; 60: De Deyn P, Rasmussen A, Bocksberger JP, et al: A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999; 53: Street J, Clark WS, Mitan S, et al: Olanzepine in the treatment of psychosis and behavioral disturbances associated with Alzheimer s disease. Presented at the 37th Annual Meeting of the American College of Neuropsychopharmacology, Las Croabas, PR, December 14 18, 1998 (abstract, p 223) 33. American Psychiatric Association: Diagnostic Criteria From DSM-IV. Washington, DC, American Psychiatric Association, Reisberg B, Borenstein J, Salob SP, et al: Behavioral symptoms in Alzheimer s disease: phenomenology and treatment. J Clin Psychiatry 1987; 48: Cummings JL, Mega M, Gray K, et al: The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994; 44: Ballard C, Holmes C, McKeith IG, et al: Psychiatric morbidity in dementia with Lewy bodies: a prospective clinical and neuropathological comparative study with Alzheimer s disease. Am J Psychiatry 1999; 156: Peyser CE, Naimark D, Langston JW, et al: Psychotic syndromes in Parkinson s disease. Seminars in Clinical Neuropsychiatry Special Issue: SecondaryPsychoses 1998; 3: Am J Geriatr Psychiatry 8:1, Winter 2000