Mohammed T. Abou-Saleh

100 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYKrishnan and colleagues 18 found patients with the ApoE3/4 alleleto have later age of onset than those with 2/3 and 3/3; conversely,Holmes et al. 19 showed that ApoE2 protected against early onset,thus delaying the onset of depression into later life; other studieswere inconclusive 20 . Although these findings conflict, the potentialto locate common genetic risk factors for depression and dementiain late life continues to receive empirical attention. Pedigreestudies have been much more univocal: elders with EODconsistently report more affected close relatives than do elderswith LOD 16,21 . Some have suggested recently that age of onsetmay be a proxy for multiple risk factors, including structuralbrain changes, vascular medical co-morbidity, neuropsychologicalimpairment, and family history of mood disorders 22 .Evidence of other non-medical risk factors for EOD and LODis preliminary. Single studies show males and African-Americansat greater risk of LOD than females and Whites, respectively 23,24 .The clinical presentations of early-onset and late-onset diseaseamong elderly patients are not strikingly different, with thepossible exceptions of more apathy, anxiety, and psychoticfeatures in LOD 21–25 . Most neurological tests also show nodifferences, with the possible exception of more impairedexecutive memory and visual naming ability in LOD 26,27 .On balance, prognosis may be slightly worse for EOD elders,although there are serious methodological difficulties with theevidence and significant heterogeneity of course in late life. Cole 28summarized conflicting early findings of differential diseasetrajectories, and studies over the subsequent decade havecontinued to conflict, some showing EOD elders to have a morerelapsing course, more frequent episodes and more treatmentrefractoriness, and others showing LOD elders to have lessfavorable treatment response, more cycling in and out of symptoms,and more psychiatric co-morbidity 29–31 . Still other studies demonstrateno difference. However, when treatment and outcomecriteria have been standardized, neither LOD nor EOD eldersappeared at increased advantage relative to absolute rates of 1 yearoutcomes (remission, relapse, recovery or recurrence), althoughweeks to remission were greater in one sample of LOD elders 22 .In a recent comprehensive review of the mortality of depression32 , only one of 57 studies compared mortality by age of onset.Rabins et al. 33 found no differences in mortality by age of onset ina small study. More recently, Philibert et al. 34 reported lowersurvival rates for subjects with LOD, especially women with onsetlater than their 6th decade.Bipolar DisorderManic symptoms and bipolar disorder (BP) I and II are rarer inthe population than depressive symptoms or MDD and are mostrare late in the life course 35 . Fewer than 1% of US elders in theECA study reported a 1 week period or more of elevated,expansive or irritable mood; lifetime prevalences of thesedisorders among persons 65 years and older were 0.1% for BPIand PBII in the same study 1 . Evidence from the UK suggests thatthe incidence of mania may be bimodal, with a detectable peakafter 60 years 36,37 . Among elderly hospitalized psychiatric populations,3.4–6.4% of all admissions and 12.5% of admissions foraffective disorders present with mania; 12–16% of general hospitalpatients qualify for a bipolar diagnosis 35 .Historically, the two potential causes of mania were thought tobe stressful life events and organic disease. Kraepelin 38 first notedthe precipitating role of stressful life events in manic depression,and subsequent studies have implicated such events in theincidence of bipolar disease, particularly early-onset mania(EOM) 39 . Late-onset mania (LOM), on the other hand, has longbeen associated with both vascular and cerebral anomalies andtheir correlates, including obesity, head injury, EEG changes anddementia, with confirmatory evidence in more recent studiescomparing older vs. younger bipolar patients 40 and LOM vs.EOM patients 39,41 . Yassa et al. 35 suggests that where significantlife events distinguish LOM patients from aged controls, anorganic substrate may have predisposed affected elders to avulnerability to such events, and they then ‘‘react with a‘catastrophic’ response (mania)’’ (p. 126).A positive family history of bipolar illness has been morecharacteristically linked with EOM than with LOM patients 39,42–44 .However, methodological problems render this generalizationsuspect. Retrospective designs, low age-of-onset cut-off points andfailure to distinguish between onset of depression vs. onset ofmania are a few of the problems limiting the evidence 43 . Evidenceof a gender differential in risk of early-onset or late-onset bipolardisorder has also been inconclusive 39 . Interracial comparisons ofage of mania onset are not available.Findings of differential clinical presentations of LOM andEOM in late life have not proved robust. The stereotype thatLOM presented more often with ‘‘slow and fragmented flights ofideas, more rarely with elated affect, but more often with paranoidand aggressive features (p. 120)’’ was not confirmed in a summaryof studies comparing the phenomenology of LOM and EOM inlate life 35 .Prognostic differences by age of first onset of mania are difficultto substantiate 45–47 . In particular, differential survival may underliethe evidence of poor outcomes associated with LOM. To thedegree that healthy social interactions are relevant to managingthe course of bipolar disorder, recent preliminary findings arenoteworthy: age of mania onset was higher among subjects withmore positive assessments of social support and receipt ofinformal instrumental support 39,45 .PSYCHOTIC DISORDERSLike affective disorders, late life psychoses (LLP) are heterogeneous,and the reach for consensus on diagnostic terminologyhas been torturous. In this summary we primarily discuss earlyonsetvs. late-onset schizophrenia (EOS/LOS), with brief mentionof delusional disorder and entirely omitting discussion ofalternative nomenclature (e.g. late paraphrenia) or subtypes lesswell characterized with respect to age of onset (e.g. schizoaffectiveand other psychotic disorders).The lifetime history of schizophrenia is probably 41% in theelderly community population 48 , with annual incidence of threenew cases (and 45 relapses) per 100 000 elders 49 . Approximately25% of elderly schizophrenics experienced a first episode after age50 50 . Onset of delusional disorder, on the other hand, occurs later,with average onset in the 40s among men and the 60s amongwomen 51 . Late-life incidence of delusional disorder is 15.6/100 000; prevalence in the elderly population is 0.04% 49 .Two powerful risk factors for LOS appear to be cerebralatrophy and brain injury, although a significant number ofpatients with late-onset LLP present with no apparent cerebralpathology 52,53 . Compared to affective disorders, there is lessevidence that EOS and LOS elders present differently with respectto MRI findings 53 or cardiovascular medical co-morbidity. Apositive family history of psychosis appears incrementally morelikely among, respectively, non-psychotic elderly controls, elderswith LOS, and elders with EOS 50 . Findings concerning ApoEdifferences in onset or phenotype are limited and inconclusive 54 .Female gender and sensory impairment may predispose toLLP 48,55 .There is considerable heterogeneity in the outcome of schizophrenicepisodes. A significant number of schizophrenic patientsimprove and recover fully; others relapse intermittently; othersremain chronically symptomatic 56,57 . Long-term studies include