Following on from the hypothesis of a role for the ApoE ε4 and ε2 alleles as risk and protective factors, respectively, for late-onset Alzheimer's disease (AD) came inevitable questions regarding other psychiatric conditions of late onset including depressive illness and schizophrenia. Is ApoE ε4 a risk factor in these diseases and do carriers have an earlier age of onset? Does ApoE ε2 have a protective role, with carriers of this allele having a later age of onset?

The dramatic and unexpected increase in life expectancy observed over the past few decades in Western countries is undoubtedly one of the great medicosocial achievements of this century. These gains have principally been made at higher ages and are reflected in the proliferation of centenarians. In France, the estimated number of centenarians was 200 in 1953, around 3,000 at the present time, and 6,000 projected for the end of the century. Similar trends are observed in the United Kingdom; the Royal Secretary sent messages of congratulations on behalf of the Queen to 300 centenarians in 1955 and to 3,300 in 1987. In parallel with these demographic observations, research on centenarians is becoming increasingly widespread with clinical and general population studies now having been conducted in France, Hungary, Japan, Italy, Finland, Denmark, the United States, and China. A database on mortality trends in the oldest old has been established by Vaino Kannisto and Roger Thatcher at the Center for Research on Aging, Odense University Medical School, providing validated data on centenarians from 12 Western European countries and Japan since 1950. Additionally, the Danish centenarian register established by Bernard Jeune contains data on centenarians back to the 1700s.

Synaptic pathology has attained increasing attention as being central in the pathogenesis of Alzheimer's disease (AD). To address the question whether synaptic pathology in AD involves the whole synapse, or is limited to specific components thereof, we studied three different synaptic vesicle proteins (rab3a, synaptotagmin, synaptophysin) and also the presynaptic membrane protein GAP-43 and the postsynaptic protein neurogranin. The material included post-mortem brain tissue (frontal cortex, hippocampus, and cerebellum) from 8 patients with early-onset AD (EAD), 11 patients with late-onset AD (LAD), 6 patients with vascular dementia (VAD), and 9 control subjects. A reduction of all synaptic proteins was found in AD, more pronounced in EAD than in LAD, in both the frontal cortex (EAD 30% to 70% vs. LAD 82% to 88% of control value) and hippocampus (EAD 22% to 82% vs. LAD 76% to 89% of control value), whereas only minor changes were found in VAD. The finding that all synaptic proteins were reduced in AD suggests a degeneration and loss of whole synaptic elements that are more pronounced in EAD than in LAD.

In order to understand what cognitive changes can be expected with aging versus those caused by disease, the New England Centenarian Study examined correlations between neuropsychological evaluation and neuropathological studies of centenarian subjects. Sixty-nine subjects were administered an extensive neuropsychological test battery designed for centenarians. Six brain donors from this group have subsequently died, and neuropathological studies of their brains have been performed to determine the presence of Alzheimer's disease (AD) and other pathological states. Of these six centenarians, three subjects had Clinical Dementia Rating scores of 0 and no dementia on neuropsychological testing, and subsequent neuropathology showed very limited AD changes. In fact, despite a range of neuropsychological findings, none of the subjects in this series met neuropathological criteria for a diagnosis of definite AD. Findings suggest that dementia is not inevitable with aging and that dementia in this age group is surprisingly often not attributable to AD.

The question of whether Mini-Mental State Examination scores should be adjusted for age and educational levels to screen for dementia in clinical populations is reexamined in the results of a recent study supporting adjustment. If the criterion is to identify the most accurate screening procedure for each sociodemographic subgroup, the evidence indicates that the unadjusted scores are preferable. Other criteria might lead to different conclusions. The validities of some of these criteria are questionable because they have the flaw that they are easily satisfied by using random decision procedures.

The accuracy of a dementia diagnosis by specialist physicians, as verified at an autopsy, is greater than 90% in many series. Donations of brains to the Maritime Brain Tissue Bank (MBTB) by individuals who did not have expert dementia diagnoses before death led us to investigate whether clinical features could also be detected retrospectively. Informants for 36 individuals whose brains were in the MBTB (18 women, mean age = 79 years; pathologic diagnoses: 75% Alzheimer's disease [AD]; 8.4% vascular or mixed dementia) were interviewed by specialist physicians using a semistructured retrospective interview based on the Brief Cognitive Rating Scale (BCRS) (range = 1 [no impairment] to 7 [terminal dementia]). The mean duration of dementia was 8.5 ± 12.8 years based on proxy reports, and most cases suggested severe dementia—(stage 6 [severe] or 7 [terminal])—on the retrospective BCRS (RetroBCRS) before death. A score of 4 or more on the RetroBCRS had 100% sensitivity and specificity in detecting dementia. The RetroBCRS score correlated moderately with duration (.51). In linear and logistic regression models adjusted for age and sex, RetroBCRS staging helped explain 93% of the variation in duration. The accuracy of the retrospective diagnosis of the cause of dementia, compared with autopsy, was 92%. The RetroBCRS used by an expert physician with a reliable informant is a valid method of detecting dementia and determining whether AD was present.

Studies of the behavioral symptoms in Alzheimer's disease (AD) would be facilitated if reliable reports could be obtained retrospectively, especially about symptoms in the final months of life when concurrent assessment is often not feasible. To evaluate such a method, we compared results of a telephone interview conducted after the patient's death with information provided by the same informant earlier, while the patient was living. Agreement between in-life and retrospective assessments was higher for psychotic symptoms than for depressive behaviors, suggesting that retrospective assessment of specific behavioral symptoms in AD is not uniformly reliable. More symptoms were retrospectively reported as the length of time between the last in-life evaluation and date of death increased, suggesting that there may be increased variety of behavioral symptoms observed by caregivers in the final stages of the disease.

The objectives of this report were to investigate the functional implications and the possible rehabilitation potentials of dementia, delirium, and psychosis in elderly inpatients, compared with that in depression. During 1 year, all patients in a psychogeriatric university clinic were assessed on admission and at discharge with a selection of rating scales and diagnosed according to ICD-10 by consultants with no knowledge of the results of the ratings. All patients who had a principal diagnosis of major depression, dementia, delirium, or a psychosis are discussed. Ratings were made for psychopathology, behavioral disorders, depressive statements, intellectual functioning, activities of daily living, and gait. Depressive and delirious patients improved their status significantly (p ≤ .03) in all six assessments, and patients with dementia improved their psychopathology status (p = .002), but the other assessments were unchanged. Results from the small sample (n = 8) of psychotic patients were mainly inconclusive, but there was a tendency for improvement with respect to psychopathology and gait.

We investigated the relationship between basal cortisol and dehydroepiandrosterone (DHEA) levels and impairment in different cognitive and noncognitive measures and the possible interaction of DHEA with hypercortisolemia in dementia in 27 patients diagnosed with Alzheimer's disease (AD). There were 17 men and 10 women. Patients were mildly to moderately cognitively impaired at the time of the initial cortisol measures. Patients were administered the Alzheimer's Disease Assessment Scale (ADAS) and Folstein Mini-Mental State Examination (MMSE) at approximately 6-month intervals. Cortisol and DHEA were determined using conventional 125I radioimmunoassay procedures. Pearson product-moment correlations among cortisol and DHEA measures and both initial and longitudinal clinical measures were calculated. There was a relationship between baseline 8 a.m. cortisol levels and cognitive function at the initial testing as measured by the ADAS cognitive measure, with higher cortisol levels being associated with a greater level of impairment. We did not document a relationship between cortisol or DHEA levels and noncognitive measures. There was a significant correlation between both the initial MMSE and ADAS cognitive measures and initial DHEA level, with lower DHEA levels unexpectedly being associated with better performance on these measures. The initial DHEA levels did not predict decline in cognitive function over time. These findings bring into question the potential usefulness of DHEA as a therapeutic agent.

The purpose of this report was to determine the impact of geriatric home screening services on mental state. Two computer databases, MEDLINE and HealthSTAR, were searched for relevant articles published from January 1975 to June 1997, and the bibliographies of retrieved articles were searched for additional references. Seven trials were located that met the four inclusion criteria: (a) original study; (b) published in English or French; (c) controlled trial (randomized or nonrandomized) of a geriatric home screening service; and (d) the trial included at least one measure of mental state. All trials met most of the validity criteria for intervention studies of the Evidence-Based Medicine Working Group. Two trials reported a small effect on morale or self-perceived health and five trials reported no effect. Thus, there was little evidence that geriatric home screening services had an impact on the mental state of aged subjects.

The purpose of this study was to assess the effects of an anticholinergic (trihexyphenidyl) antiparkinsonian medication on the Mini-Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG) scores in long-term institutionalized elderly patients with schizophrenia. Seventeen schizophrenic (DSM-III-R) inpatients on long-term medication who had received trihexyphenidyl for at least 6 consecutive months were compared for MMSE scores, CAMCOG scores, and other demographic and clinical variables with 14 patients not receiving any anticholinergic agent for the same time period. Results showed that age, years of education, illness duration, length of current hospital stay, the Manchester Scale scores, and chlorpromazine daily equivalent dose in mg were not different in the two groups compared. Extrapyramidal signs such as tremor, rigidity, and bradykinesia were more frequent in trihexyphenidyl receivers. The scores of MMSE (p ≤ .007) and CAMCOG (p ≤ .005) and CAMCOG subscales of orientation (p ≤ .03), language (p ≤ .01), and memory (p ≤ .002) were significantly lower among trihexyphenidyl receivers, as was the Social and Occupational Functioning Assessment Scale score (p ≤ .05). In addition, the MMSE and CAMCOG scores were significantly lower for patients receiving 10 mg of trihexyphenidyl a day compared with those receiving 5 mg/day and nonusers. It is suggested that trihexyphenidyl in usual clinical doses may impair total MMSE and CAMCOG scores as well as some of the CAMCOG subscales in this patient population. However, only a prospective study, preferably double-blind and controlled, with measures of change will validate this conclusion.