Mohammed T. Abou-Saleh

506 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYconsidered unusual in such settings 19 . Moreover, Watt 20 , in astudy of 35 patients, found no association between hearing lossand paranoid psychosis manifesting in middle life. It might be thatpsychosis occurs only in individuals who are already prone toparanoid ideation, e.g. by virtue of mild cerebral damage. This isconsonant with findings in an elderly general population sample 21 ,of an association between persecutory ideation, sensory impairmentand cognitive dysfunction.‘‘ORGANIC’’ FACTORSAcute paranoid ideation may result from cerebral or extracerebralorganic factors, and the elderly are especially susceptible to sucheffects. More persistent delusional persecutory states are seen inassociation with a wide variety of structural brain changes andsystemic toxic and metabolic disturbances. In particular, suchstates can occur in dementia. For example, Wragg and Jest 22 ,inareview of studies reporting the prevalence of psychotic phenomenain patients with Alzheimer’s disease, found a rate of delusionsof anything from 10% to 73% (aggregating to 30–38%, with amedian of 33.5%). For hallucinations, the range was 21–49%(mean 28%). The importance of organic factors in the aetiogenesisof psychotic phenomena in the elderly is underlined by generalpopulation studies, which have consistently found the strongestpredictor of paranoid ideation in the elderly to be cognitiveimpairment 23,24 .Kay 25 stated that a diagnosis of late-onset schizophrenia can bemade only in the absence of ‘‘gross and persistent disorientation intime and place or severe failure of memory’’. Roth 1 claimed thathis follow-up data validated the separation of such disorders fromthe dementias, while Kay and Roth 26 found only minimalevidence of organic cerebral damage in their late paraphrenicpatients. Subsequently, Kay 25 reported survival rates for lateparaphrenia patients of 0.97:1 (observed expected), comparedwith 0.3:1 for patients with dementia.However, it is becoming increasingly clear that a significantnumber of elderly patients with ‘‘functional’’ paranoid states dohave evidence of organic cerebral deterioration, not part ofordinary ageing. For example, Post 14 reported that some 15% ofhis patients were demented at follow-up, while Holden 6 found that13 (35%) of 37 late paraphrenia patients had demented within 3years of diagnosis; the only distinguishing feature on admissionwas a slight impairment on psychometric assessment in the‘‘organic’’ group.Neuroimaging investigations have revealed structural brainchanges in a proportion of elderly patients with persistentpsychosis and no obvious neurological or neuropsychologicaldeficit. Miller and colleagues 27 reported three such patients whohad CT scan evidence of cerebral infarction and one with normalpressure hydrocephalus. In a prospective CT and MRI study of 27patients with late-life psychosis, Miller et al. 28 found silentvascular lesions in five (19%); subcortical frontal connectionswere most commonly involved. Similarly, Jernigan et al. 29reported 13 patients with late-onset psychosis (10 schizophrenia,three delusional disorder) to have significantly more white-matterpathology on MRI than age-matched normal controls; andBreitner et al. 30 found significant leucoencephalopathy, especiallyaffecting the temporoparietal and occipital regions, in eight lateonsetschizophrenia patients; such lesions were minimal or absentin controls.These findings may provide useful information about thepathogenesis of late-onset schizophrenia. However, the exactrelationship of the reported lesions to the manifestation of thedisease is unclear. There is little consistency in the site of thelesions, and white-matter changes have also been reported inelderly patients with severe depression 31 . Moreover, it appearsthat when late-onset schizophrenia patients are clinically screenedfastidiously, so as to exclude any patients with potential ‘‘organic’’aetiologies, they show no excess of white matter abnormalitiescompared to controls 32 .NON-SPECIFIC STRUCTURAL BRAINABNORMALITIESNumerous neuroimaging studies have revealed an increase inventricular:brain ratio (VBR) in younger schizophrenia patientscompared with normal controls. These findings, and thosesuggesting temporal lobe dysplasia, appear to have a developmentalorigin. There are few such studies in late-onset patients.Rabins et al. 33 studied 29 schizophrenia patients with disease onsetafter the age of 44, and found mean VBR to be greater than formatched normal controls. Naguib and Levy 34 reported similarfindings in 43 late paraphrenia patients; there was no correlationbetween illness duration and ventricular size, and ventricular sizedid not predict disease outcome at a mean of 3.7 years 35 .InanMRI study, Jeste and Harris 36 confirmed an increase inventricular size in 20 late-onset schizophrenia patients comparedwith normals. Again, there was no relationship between illnessduration and ventricular size, suggesting that the abnormalitypreceded disease onset and was not progressive. In an attempt tocorrelate brain imaging findings with clinical symptomatology,Howard and colleagues 37 reported that ventricular/sulcal enlargementwas most dramatically evident in those late paraphreniapatients who did not manifest Schneiderian first-rank symptoms.The relationship between neuroimaging findings in early- vs.late-onset schizophrenia patients remains a moot point. Pearlsonet al. 38 compared 11 late-onset with 11 early-onset schizophreniapatients, and found no significant differences between the groupsin terms of volume of a number of brain structures. Summarizingthese and other such data, Pearlson 39 concluded that ‘‘early- andlate-onset cases of schizophrenia share common structural ...brain abnormalities’’. But the significance of these findings isunclear. It seems very unlikely that they have a similardevelopmental origin to the equivalent abnormalities in earlyonsetschizophrenia. Indeed, a comparative study of very early(525 years) and very late-onset (460 years) schizophreniapatients found that the latter group did not seem prone to thoserisk factors (e.g. obstetric complications) that have beenimplicated in the aetiology of the neurodevelopmental form ofschizophrenia 40 . Presumably, the ventricular enlargement is oflittle consequence in its own right, being merely an echo of someundetected cerebral lesion. Burns et al. 41 have suggested that thereoccurs, in late paraphrenia, an ‘‘uncoupling’’ of the normalassociation between ventricular and cortical size, but the exactmechanism whereby this results in psychotic symptoms is unclear.There is a place for further studies in this area. Specifically, furtherattempts should be made to find clinical correlates of enlargedventricles, and to assess predictive value in longer-term follow-upstudies. The use of more advanced neuroimaging techniques tosearch for more specific abnormalities will also be important.CONCLUSIONSMany authors consider late-onset schizophrenia to be ‘‘a form ofschizophrenia, albeit attenuated and modified’’. One suggestion isthat inherent genetic vulnerability, itself insufficient to causepsychosis, acts in concert with environmental factors (socialisolation, sensory impairments, non-specific brain atrophy) toprecipitate delusional breakdown. Paranoid/schizoid premorbidpersonality traits might be an expression of such intermediategenetic loading.