Tony Hope

Predictors of institutionalization for people with dementia living at home with a carer.

Objective. This article examines the relationships between behaviour, psychological functioning, the caring environment and subsequent institutionalization in patients with dementia living at home with a carer.

Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up.

Abstract Objective: To investigate the contribution of neuroleptic drugs to cognitive decline in dementia. Design: Two year prospective, longitudinal study consisting of interviews every four months, with necropsy follow up. Setting: Community settings in Oxfordshire. Subjects: 71 subjects with dementia, initially living at home with informant. Main outcome measures: Cognitive function (score from expanded minimental state examination); behavioural problems (physical aggression, hallucinations, persecutory ideas, and disturbance of diurnal rhythm); and postmortem neuropathological assessment (cortical Lewy body pathology). Results: The mean (SE) decline in cognitive score in the 16 patients who took neuroleptics was twice that in the patients who did not (20.7 (2.9) v 9.3 (1.3), P=0.002). An increased rate of decline was also associated with aggression, disturbed diurnal rhythm, and persecutory ideas. However, only use of neuroleptics and severity of persecutory ideas were independently associated with more rapid cognitive decline when all other variables were adjusted for. The start of neuroleptic treatment coincided with more rapid cognitive decline: median rate of decline was 5 (interquartile range 8.5) points per year before treatment and 11 (12) points per year after treatment (P=0.02). Cortical Lewy body pathology did not account for association between neuroleptic use and more rapid decline. Conclusions: Neuroleptic drugs that are sometimes used to treat behavioural complications of dementia may worsen already poor cognitive function. Randomised controlled trials are needed to confirm a causal relation. Key messages Neuroleptic drugs are used to treat behavioural problems in patients with dementia, but they may cause more rapid decline in cognitive function In our longitudinal study of patients with dementia we found that the rate of cognitive decline in patients taking neuroleptics was twice that in those not taking neuroleptics Furthermore, the start of neuroleptic treatment was associated with an increase in the rate of cognitive decline Cortical Lewy body pathology at necropsy did not account for the association between neuroleptic use and more rapid decline Although our study does not prove a causal relation, we suggest that there should be regular review of the need for patients to continue taking neuroleptic drugs

Psychiatric disorder and personality factors associated with suicide in older people: a descriptive and case-control study.

To determine the rates of psychiatric disorder and personality variables in a sample of older people who had committed suicide and to compare the rates in a subgroup of this sample with those in a control group of people who died from natural causes.

Cholinergic deficits contribute to behavioral disturbance in patients with dementia

Background: Noncognitive behavioral changes such as depression, aggressive behavior, psychosis, and overactivity occur frequently in patients with dementia, in addition to cognitive impairment, and often determine the need for institutionalization. The biochemical basis of such changes is poorly understood. Clinical trial data indicate that cholinomimetics improve noncognitive behaviors. This study investigated the relationship between markers of the cholinergic and dopaminergic neurotransmitter systems and noncognitive behavioral symptoms assessed during the course of dementing illness. Method:— Brains from 46 patients with dementia (36 with AD and 10 with mixed or other dementias using Consortium to Establish a Registry for AD criteria) were examined together with 32 normal controls. The patients with dementia had been evaluated every 4 months, often over several years, for cognitive performance (Mini-Mental State Examination) and behavior (Present Behavioral Examination). Concentrations of dopamine (DA) and major metabolites, choline acetyltransferase activity (ChAT), and density (Bmax) of DA D1 receptors in frontal and temporal cortex were studied by radioligand binding protocols. None of the patients was receiving cholinomimetic drugs. Results: ChAT activity, but no other neurochemical markers, was reduced in AD compared with controls. Loss of ChAT activity correlated with cognitive impairment. Lowered ChAT activity also correlated with increasing overactivity in patients with dementia in both frontal and temporal cortex whereas ChAT:DA and ChAT:D1 ratios in temporal cortex correlated negatively with aggressive behavior. Conclusions: Disturbance of the cholinergic system may underlie both cognitive and some noncognitive behavioral changes in dementia, providing a basis for rational therapy.–1467

Reduced serotonin 5-HT1A receptor binding in the temporal cortex correlates with aggressive behavior in Alzheimer disease

Previous studies have implicated brain serotonin 5-HT(1A) receptors in several CNS functions, including cognition, mood and emotional states. In Alzheimer disease (AD), cognitive impairment and behavioral symptoms are the main clinical features. However, the biochemical basis of such changes is poorly understood. Results from recent in vivo studies suggest that 5-HT(1A) receptors may be related to aggressive traits in healthy subjects. The present study investigated the state of 5-HT(1A) receptors in the postmortem neocortex of 33 AD patients prospectively assessed for cognition and behavioral symptoms, together with 20 matched controls, by saturation [(3)H]8-OH-DPAT binding assays. 5-HT(1A) receptor binding affinity (K(D)) and density (B(max)) were unchanged in the overall AD group compared with controls. Within the AD group, 5-HT(1A) receptor B(max) in the temporal cortex inversely correlated with aggression and dementia severity. However, multiple regression analyses showed that 5-HT(1A) receptor B(max) remained the best predictor for aggression, while temporal cortical neurofibrillary tangle grading was the best predictor for dementia severity. This suggests that 5-HT(1A) receptor alteration is directly related to aggression in AD, while dementia severity is more strongly related to the neurodegenerative process. Our data indicate further study of 5-HT(1A) receptors as a pharmacological target for the treatment of behavioral symptoms in AD.

Suicide in older people: Mode of death, demographic factors, and medical contact before death

To determine the demographic characteristics, mode of death, and nature and timing of medical contacts in the year before death in a sample of suicides in older people.

Psychosis of Alzheimer’s disease is associated with elevated muscarinic M2 binding in the cortex

Objectives: Results from recent drug trials suggest a role for the cholinergic system in the manifestation of neuropsychiatric symptoms in AD. To date, the status of muscarinic acetylcholine receptor subtypes in AD in relation to accompanying behavioral disturbances is unknown. This study aimed to measure alterations of muscarinic M1 and M2 receptor binding in the frontal and temporal cortex of AD and to correlate the neurochemical findings with clinical features. Methods: The cognitive and behavioral features of 26 patients with AD were assessed prospectively using standardized tests. Together with 14 matched controls, the status of muscarinic M1 and M2 receptors in the postmortem frontal and temporal cortex of these patients were measured by radioligand binding assays and were correlated with clinical data. Results: Compared with controls, M2 receptor density was reduced only in the frontal cortex of AD, whereas M1 was unaffected. Within the AD group, the neurochemical variables were not affected by demographic factors, disease severity, or cognition. Instead, M2 receptor density was increased in the frontal and temporal cortex of patients with AD with psychotic symptoms compared with those without these symptoms. Conclusions: This study suggests a role for M2 receptors in the psychosis of AD and may provide the rationale for treatment of behaviorally perturbed patients with AD with cholinomimetics and M2 antagonists.

The Present Behavioural Examination (PBE): the development of an interview to measure current behavioural abnormalities.

Behavioural problems are an important feature of dementia and other neuropsychiatric conditions. This paper describes the development and performance of an investigator-based interview (the PBE) for the detailed assessment of the behaviour of subjects over the preceding four weeks. The interview is designed to be administered to carers. A test-retest reliability study was carried out on the penultimate edition of this interview; and the inter-rater reliability of the final edition was measured. These studies show that the reliability of the PBE is comparable with that of other investigator-based interviews.

Behaviour changes in dementia 2: Are there behavioural syndromes?

Objective. To establish whether robust behavioural ‘syndromes’ can be identified from among the widely heterogeneous behavioural changes which occur in dementia.

Life problems and physical illness as risk factors for suicide in older people: a descriptive and case-control study

BACKGROUND The role of physical illness and life problems in contributing to suicide in older people is potentially important with regard to suicide prevention. METHOD The aim of the study was to determine the life problems other than psychiatric illness contributing to suicide in older people. Semi-structured psychological autopsy interviews, covering life problems and physical illness prior to death, were conducted with informants for 100 people aged 60 years old and over who died through suicide in five English counties. Interviews were completed with informants for 54 age- and sex-matched control subjects who died through natural causes. RESULTS The three most frequent life problems associated with suicide were physical illness, interpersonal problems, and bereavement. Physical health problems were present in 82% and felt to be contributory to death in 62%. Pain, breathlessness and functional limitation were the most frequent symptoms. Interpersonal problems were present in 55% of the sample and contributory in 31%. The corresponding figures for bereavement-related problems were 47% and 25%. In the case-control analysis, the problems found to be risk factors for suicide were problems related to a bereavement over 1 year before death (OR 3.5, 95% CI 1.2-10.6), and problems with accommodation (OR 5.0, 95% CI 1.1-22.8), finances (p=0.01), and retirement (p=0.02). CONCLUSION Physical illness, interpersonal problems and bereavement are commonly associated with suicide in older people, but financial, accommodation, retirement and long- term bereavement-related problems may be more specific risk factors.