Perception, attention, and working memory are disproportionately impaired in dementia with Lewy bodies compared with Alzheimer's disease.

OBJECTIVE: To test the hypotheses that visuoperceptual and attentional ability are disproportionately impaired in patients having dementia with Lewy Bodies (DLB) compared with Alzheimer's disease (AD). METHODS: A comprehensive battery of neuropsychological tasks designed to assess working, episodic, and semantic memory, and visuoperceptual and attentional functions was given to groups of patients with DLB (n=10) and AD (n=9), matched for age, education, and mini mental state examination (MMSE), and to normal controls (n=17). RESULTS: Both patient groups performed equally poorly on tests of episodic and semantic memory with the exception of immediate and delayed story recall, which was worse in the AD group. Digit span was by contrast spared in AD. The most striking differences were on tests of visuoperceptual/spatial ability and attention. Whereas patients with AD performed normally on several subtests of the visual object and space perception battery, the DLB group showed substantial impairments. In keeping with previous studies, the AD group showed deficits in selective attention and set shifting, but patients with DLB were more impaired on virtually every test of attention with deficits in sustained, selective, and divided attention. CONCLUSIONS: Patients with DLB have substantially greater impairment of attention, working memory, and visuoperceptual ability than patients with AD matched for overall dementia severity. Semantic memory seems to be equally affected in DLB and AD, unlike episodic memory, which is worse in AD. These findings may have relevance for our understanding of the genesis of visual hallucinations, and the differential diagnosis of AD and DLB.

Population norms for the MMSE in the very old: estimates based on longitudinal data. Mini-Mental State Examination.

OBJECTIVE: To report the percentile distribution of Mini-Mental State Examination (MMSE) scores in older people by age, sex, and education level, estimated from longitudinal data, after correcting for loss due to dropout. METHODS: The Cambridge City over 75 Cohort is a population-based study of a cohort of 2106 subjects age 75 years and older at study entry followed up over 9 years. At each of the four waves, cognitive function was assessed using MMSE. Based on these data, the relationship between age and MMSE score was modeled. Percentile distributions by age, sex, and education level were provided using inverse probability weighting to correct for dropouts. RESULTS: Performance on MMSE was related to age in men and women. In women, at age 75, MMSE score ranged from 21 (10th percentile) to 29 (90th percentile). At age 95, the range was 10 (10th percentile) to 27 (90th percentile). The upper end of MMSE distribution was slightly modified with age, whereas the lower end of the distribution was very sensitive to age effect. A similar pattern was observed in both sexes. CONCLUSION: These findings provide norms for MMSE scores in subjects age 75 years and older from longitudinal population-based data. Such norms can be used as reference values to determine where an individual's score lies in relation to his or her age, sex, and education level.

Very old drivers: findings from a population cohort of people aged 84 and over.

BACKGROUND: Increases in longevity will involve a significant increase among the number of drivers in the very old, who are at greater risk of being involved in road accidents. Data are thus needed from studies of older populations to characterize those still driving, the reasons for giving up and to help formulate appropriate policies for dealing with the problems faced and created by an increase in older drivers. METHODS: A driving questionnaire was administered to surviving members of a cohort comprising a representative sample of individuals aged >/=84, the Cambridge City over 75 Cohort. Out of 546 survivors 404 completed the driving questionnaire at the 9-year follow-up. In addition, subjects were assessed, at baseline and at each follow-up, for cognitive performance using the Mini-Mental State Examination (MMSE) and for physical impairment using the Instrumental of Activities in Daily Living (IADL) scale. RESULTS: Of the sample, 37% had driven in the past, and 8.4% were still driving, the majority regularly. The drivers tended to be younger (mean age 86.6 years), men (71%) and to be married (67.7%). Although physical disability and cognitive impairment are common in this age group, current drivers had few physical limitations on their daily activities and were not impaired on MMSE. None of the current drivers had visual impairment and 22.6% had hearing loss. Of those who had given up driving, 48.5% had given up at the age of >/=80. The commonest reasons for giving up driving were health problems (28.6%), and loss of confidence (17.9%). One-third reported giving up driving on advice. CONCLUSION: A process of self-selection takes place among older drivers. People over the age of 84 who are still driving have generally high levels of physical fitness and mental functioning, although some have some sensory loss. Given the likely increase in the number of older drivers over the next decades, safety will be improved most by strategies aimed at the entire driving population with older drivers in mind, rather than relying on costly screening programmes to identify the relatively small numbers of impaired older people who continue to drive.

Estimating the true extent of cognitive decline in the old old.

OBJECTIVE: To measure cognitive change using a brief measure over a period of 9 years and to adjust for attrition in the sample. DESIGN: The Cambridge City over 75 Cohort (CC75C), a complete sample of the 75 years and older age group from five group general practices in the city of Cambridge with a systematic one-third of a further practice, all followed on four occasions. SETTING: Cambridge city, UK, the respondents' place of residence. PARTICIPANTS: A total of 2106 subjects were included at study entry. MEASUREMENTS: A brief interview, administered by a trained interviewer, containing a short cognitive scale and the Mini-Mental State Examination (MMSE) at baseline, 2.4 years, 6 years, and 9 years. RESULTS: Decline in MMSE scores occurred across the population and was greater in the oldest age groups. Attrition at later stages of the follow-up was associated with greater decline at earlier stages. Adjusting the results for loss to the sample leads to considerably higher estimates of decline, with the older age groups declining faster from lower levels. CONCLUSIONS: To date, cognitive decline in the very old has been considerably underestimated by longitudinal studies. If studies of population samples are to reflect the health and social needs of this frail group accurately, adjustments for the effect of attrition must be included before true decline can be estimated.

Changes in self-rated health, disability and contact with services in a very elderly cohort: a 6-year follow-up study.

OBJECTIVES: To study the relationships between global self-rated health, reported physical symptoms and depressive symptoms and the receipt of community services by very elderly people, and to examine changes in these variables over time. DESIGN: Three-wave study with follow-up at 2.4 and 6 years after first interview. Structured interview, incorporating cognitive examination (Mini-Mental State Examination) and enquiring specifically about overall self-rated health, physical symptoms and depressive symptoms. SETTING: Community setting in city of Cambridge, UK. PARTICIPANTS: 2609 were initially recruited: all patients aged 75 years and over from lists of six general practices (and one in three from a seventh practice). At 2.4 years, 1173 individuals re-examined and at 6 years 628 individuals. MEASUREMENTS: General health self-rated in comparison to others of similar age and individual physical and depressive symptoms self-rated as present or absent. Symptoms were added to produce physical health and depressive symptom scores. Data presented from cross-sectional analysis of 6-year sample; also examined longitudinal data from all three waves of study for ageing and cohort effects. Finally the effect of health variables on the receipt of services was examined. Statistics used included chi(2) and non-parametric statistics for continuous data, also odds ratios for likelihood of receiving services. RESULTS: At 6 years, 70% rated their overall health as good or very good. Overall self-rated health showed both ageing and cohort effects, improving with increasing age and especially with more recent cohort. Reported physical symptoms increased with ageing. Depression scores also increased with ageing but the relationship between depressive symptoms and ageing was less clear-cut. Receipt of services was associated with poor self-rated health and reported physical symptoms as well as with ageing. Higher depression scores at 2.4 years were associated with increased service receipt at 6 years, indicating a lag between the symptoms and the service response. Individuals in the more recent cohort were less likely to receive services, but those who did so received more frequent contact. CONCLUSIONS: Although very elderly people have a high prevalence of reported physical symptoms, they often rate their overall health as good. There was a stronger relationship between ageing and physical symptoms than with depressive symptoms. Symptoms of both kinds influenced the likelihood of receiving services, although there was a lag between depressive symptoms and service response. Cohort effects on service receipt may reflect changes in public service policy.

Analysis of the apo E/apo C-I, angiotensin converting enzyme and methylenetetrahydrofolate reductase genes as candidates affecting human longevity.

Genetic factors are likely to affect human survival, since twin studies have shown greater concordance for age of death in monozygotic compared to dizygotic twins. Coronary artery disease is an important contributor to premature mortality in the UK. Accordingly, we have chosen genes associated with cardiovascular risk, apo E/apo C-I, angiotensin converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR), as candidates which may affect longevity/survival into old age. An association study was performed by comparing allele and genotype frequencies at polymorphic loci associated with these genes in 182 women and 100 men aged 84 years and older with 100 boys and 100 girls younger than 17 years. MTHFR allele and genotype frequencies were similar in the elderly and young populations. Apo C-I allele and genotype frequencies were significantly different in the elderly women compared to the younger sample (P < 0.05). No difference was observed in the elderly men. At the neighbouring apo E gene, we only observed a difference between genotypes in the elderly women and the young sample; however, this did not retain significance when the genotype frequencies of the young sample were adjusted to values expected from the allele frequencies on the basis of Hardy-Weinberg equilibrium and compared to observed genotypes in elderly men and women. In contrast to previous studies, apo E2 was not overrepresented in the elderly men or women. Thus, the proposition that apo E2, E3 and E4 protein isoforms are themselves functionally associated with increasing risks for early death, may be too simplistic. The I/I ACE was depleted in the elderly males but not the elderly females. Furthermore, significant differences were observed between ACE genotypes in elderly men and elderly women. These data suggest that the penetrance of loci which influence survival may vary according to sex. The depletion of the ACE I/I genotype in elderly men is generally consistent with a previous study which found decreased frequencies of the I allele in French centenarians compared to younger controls. However, these results are apparently paradoxical, since others have suggested that the I allele is associated with increased cardiovascular risk. Clarification of the overall effect of a genotype on survival will be vital if therapies are to be considered which target specific genetic variants.

Pseudohallucinations: a conceptual history.

The term 'pseudohallucination' is currently used to name imaginal experiences whose relationship to one another and to hallucinations 'proper' remains obscure. Clinicians, including specialists in psychopathology, disagree on how pseudohallucination must be defined and on its diagnostic role. Empirical research is unlikely to help as the term does not have a stable referent. Historical and conceptual analyses, on the other hand, are of great use to show how this untidy state of affairs has obtained. This paper includes a full account of the history of pseudohallucination and concludes that: (a) the problem has resulted from the fact that the history of the word, concept(s) and putative behaviour(s) failed to 'converge' (i.e. there never has been a time when the three components have formed a stable complex); (b) failure to converge has been caused by the fact that the concept of pseudohallucination is parasitical upon that of hallucination, and that the latter has proved to be far more unstable than what is usually recognized; (c) hence, pseudohallucination is a vicarious construct (i.e. one created by a temporary conceptual need, and which is not associated with a biological invariant); (d) pseudohallucination is used as the 'joker' in a poker game (i.e. made to take diagnostic values according to clinical need)- this has led to diagnostic complacency and retarded important decisions as to the nature and definition of hallucinations; and (e) the language of current descriptive psychopathology is not fine-grained enough to generate a stable frame for pseudohallucination. This suggests that its boundaries and usage will remain fuzzy and unbridled.

Quality of life and medicine: a historical note.

This paper analyses the historical origins of the concepts of welfare as a positive right and of quality of life. The latter has historical antecedents but has become important in the latter half of the twentieth century, owing to the conflict between consumer demands for medicine and constraints upon spending. It is argued that, beyond the immediate economic and utilitarian contexts, the concept of quality of life has the potential to promote individual liberty and a more subjectively-based approach to medicine.

Depression-related cognitive impairment: possibilities for its pharmacological treatment.

Depression-related cognitive impairment (DRCI) is a condition which despite its initial treatment response, shows a progressive deterioration. No consistent therapeutic strategies have been proposed to combat this condition. This may be due to a reluctance to treat the cognitively impaired, a failure to recognise the deleterious prognosis or a poor understanding of the likely pathogenesis. Increasing evidence implicates the hypothalamo-pituitary-adrenal (HPA) axis as a key neurobiological determinant of the presentation and course of depression-induced cognitive decline. By utilising agents which control central glucocorticoid hyperactivity over a sustained period, whilst avoiding those agents which may compromise cognitive abilities, there exists a pharmacological strategy which may minimise the morbidity of cognitive impairment related to depressive illness.

The enigma of pseudohallucinations: current meanings and usage.

This study investigates the view of 2 samples of psychiatrists about pseudohallucinations (PH) and their perceived value in clinical practice. Among UK and Irish consultant psychiatrists, 87% expressed belief in PH, but 63% thought that the concept was confusing and only 58% thought PH were clinically useful. Recently appointed consultants were more positive about PH. One-third of respondents were sceptical: and even the more enthusiastic gave variable and inconsistent responses. Many psychiatrists do not value the concept of PH or do not use it. Those who do favour it use it inconsistently. The concept gives rise to much confusion, and is weak because it is defined negatively. It should be abandoned in favour of a more precise clinical approach to describing false perceptions.

The Cambridge Neurological Inventory: a clinical instrument for assessment of soft neurological signs in psychiatric patients.

A schedule (the Cambridge Neurological Inventory) has been constructed for standardized neurological assessment of psychiatric patients. Normative data and data resulting from its application to a group of patients with schizophrenia are reported. The instrument is comprehensive, reliable, and easy to administer. In conjunction with other forms of clinical assessment, it may be useful for identifying soft neurological signs and other patterns of neurological impairment relevant to neurobiological localization and prognosis in schizophrenia and other psychiatric disorders.

Autoscopic phenomena.

BACKGROUND: Autoscopy is defined here as a visual experience where the subject sees an image of him/herself in external space, viewed from within his/her own physical body. This paper reviews the literature both historically and conceptually, and includes a quantitative study of accumulated cases. METHOD: Cases published since 1935 and meeting the above definition for autoscopy (n = 53) were included, together with three personally-observed patients. A clinical protocol was completed for each case, including information about the autoscopic image. Cases were compared using non-parametric statistics on dichotomised variables. RESULTS: There were 38 men and 18 women, with a mean age of 39.5 years (range 13-78). Of the subjects, 33 (59%) had a neurological illness, most frequently epilepsy (18 cases). Right and left sided lesions were equally represented. Psychiatric disorder was often present (33 cases, 59%), most commonly delirium, depression or psychosis. The features of the images seen were diverse, but speaking images were associated with younger age, male sex, psychotic illness, longer duration of image, and hypnagogic/hypnopompic experiences. CONCLUSIONS: Autoscopy may arise from a convergence of several variables, including gender, personality factors, neurological and/or psychiatric disease, exhaustion and dissociation, whose interaction may override the normal inhibition of temporal lobe activity. A cognitive neuropsychological hypothesis is proposed, together with avenues for future research.

Feelings of guilt in major depression. Conceptual and psychometric aspects.

A new scale for the evaluation of feelings of guilt is described. Two types of guilt feeling were of potential interest: 'delusional' guilt or shame (experienced in relation to one's actions), and 'affective' guilt (a more general feeling of unworthiness). Reliability and validity analyses for the first (15-item) version of the scale were performed in three separate and contrasting clinical samples. The second and final (seven-item) version was tested in another sample of major depressives and in normal controls. The HRSD was used as a measure of severity throughout. The BDI and Widlöcher psychomotor retardation scale were also used as external criteria for the seven-item scale. Exploratory factor analysis of this sample yielded two factors--'cognitive/attitudinal' and 'mood/feeling'--of which only the first correlated with scores for psychomotor retardation. It is suggested that these two factors represent two forms of guilt, but that only the former is related to a putative dopaminergic disorder. Guilt scores and measures of severity were not correlated. It is suggested that feelings of guilt should be considered as a behavioural marker for a subtype of depression.

The neuropsychiatry of Wilson's disease: a review.

Psychiatric symptoms are frequently encountered in Wilson's disease (WD). The recent resurgence of interest in neuropsychiatry has led to a more detailed consideration of the psychopathology associated with WD. As suggested by Wilson, disorders of affect, behavior and personality are the most common features. Contrary to Wilson's view, recent evidence suggests that such symptoms have an organic basis. Cognitive impairments tend to be mild and improve with treatment. There is a lack of recent evidence for an association between WD and organic delusional disorders.

Wilson's disease: a longitudinal study of psychiatric symptoms.

One hundred and twenty-nine cases of Wilson's disease (WD) were assessed at index admission and two follow-ups (F1 and F2) on a range of clinical and biochemical variables. The commonest psychiatric symptoms throughout were incongruous behavior, irritability, depression, and cognitive impairment. Among psychiatric cases, most improvements occurred in the interval index-F1, with subsequent leveling off. Significant improvement occurred only with incongruous behavior and cognitive impairment. Psychiatric cases whose psychiatric symptoms persisted to F2 differed from those who responded, in particular showing more dysarthria, incongruous behavior, and hepatic symptoms. Neuropsychiatric cases displayed more dysarthria and incongruous behavior than patients with neurological symptoms alone. Further evidence for associations between dysarthria and abnormal behavior emerged from this study.