ABSTRACT
OBJECTIVE: To investigate in a longitudinal cohort of people with Alzheimer's disease whether taking antipsychotics is associated with more rapid cognitive deterioration. METHOD: From a sample of 224 people with Alzheimer's disease recruited as epidemiologically representative, those taking antipsychotic drugs for more than 6 months were compared with those who were not, in terms of change in three measures of cognition. The effects of potential mediators and confounders (demographic factors, neuropsychiatric symptoms, cognitive severity and cholinesterase inhibitors) were also examined. RESULTS: No significant difference was observed in cognitive decline between those taking antipsychotics (atypical or any) and others on any measure of cognition. The only predictor of more cognitive decline was greater baseline cognitive severity (B = 3.3, 95% confidence interval 0.6 to 6.1, t = 2.4, p<0.05). Although mortality was higher in those treated with antipsychotics, this reflected their greater age and severity of dementia. The results were the same when the whole cohort was included rather than the select group with potential to change who had been taking antipsychotics continuously. CONCLUSIONS: In this, the first cohort study investigating the effects of atypical antipsychotics on cognitive outcome in Alzheimer's disease, those taking antipsychotics were no more likely to decline cognitively over 6 months. Although clinicians should remain cautious when prescribing antipsychotic drugs to people with Alzheimer's disease, any increase in cognitive deterioration is not of the magnitude previously reported. There is a need for cohort studies that follow up patients from first prescription in clinical practice for a period of months rather than weeks to determine "real-life" risks and benefits.
Subject(s)
Alzheimer Disease/drug therapy , Alzheimer Disease/psychology , Antipsychotic Agents/adverse effects , Cognition Disorders/etiology , Aged , Aged, 80 and over , Alzheimer Disease/complications , Antipsychotic Agents/therapeutic use , Disease Progression , Female , Humans , Longitudinal Studies , Male , Severity of Illness IndexABSTRACT
The objective was to explore caregivers' experience of and concerns about the safety of care recipients (CRs) with Alzheimer's disease (AD) living at home. We interviewed family caregivers about their concerns regarding CR's safety, occurrence of risk over the last year and safety measures taken to manage risk. A total of 89 family caregiver/CR dyads participated. All had been recruited as part of a larger longitudinal study based in London and South East Region (LASER) of the UK. Caregivers spent a substantial proportion of the day supervising the CR (mean = 15.5 hours). Most caregivers (39; 81.2%) of the 48/89 CRs left alone worried about their safety. Sixty-one (68.5%) caregivers reported at least one incident in which the CR had been at risk within the past year. A majority (71; 79.8%) had taken measures to prevent risk behaviours. Greater impairment in activities of daily living and the caregiver not being the CR's spouse were associated with more measures being taken. Caregivers themselves provide supervision most of the time for the CR, and are worried when they are left alone. This is realistic as despite caregiver's attempts at managing their CR's risks, including direct supervision, dangerous incidents still frequently occur in people with AD.
Subject(s)
Alzheimer Disease/therapy , Anxiety/epidemiology , Caregivers/psychology , Caregivers/statistics & numerical data , Safety Management , Surveys and Questionnaires , Activities of Daily Living , Aged , Aged, 80 and over , Anxiety/psychology , Demography , Depression/epidemiology , Depression/psychology , Female , Follow-Up Studies , Harm Reduction , Humans , Male , Middle Aged , Risk FactorsABSTRACT
OBJECTIVE: To study the nigrostriatal pathways in 21 patients with dementia with Lewy bodies (DLB), 19 drug naive Parkinson disease (PD) patients, and 16 controls using a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) and SPECT in order to assess similarities or differences between DLB and PD. METHODS: A SPECT scan was carried out 3 to 4 hours after administration of 185 MBq (IV) of FP-CIT. Using occipital cortex as a radioactivity uptake reference, ratios for the caudate nuclei and the anterior and posterior putamina of both hemispheres were calculated. From the FP-CIT binding measurements, asymmetry indices and caudate:putamen ratios were derived. RESULTS: The DLB and PD groups had lower FP-CIT binding in all striatal areas than controls (analysis of variance: p < 0.001 in all measures). DLB patients also had significantly lower binding in the caudate nucleus than the PD patients. There was greater asymmetry of uptake in the posterior putamina of PD patients than DLB patients (p < 0.04) and controls (p < 0.01). The mean caudate:putamen ratio for the DLB group was not significantly different from that of the controls, while the mean caudate:putamen ratio of the PD group was higher than that of the control group (p < 0.001) and the DLB group (p < 0.001). CONCLUSION: This study showed differences between PD and DLB in the pattern of striatal dopaminergic dysfunction. DLB patients do not have the characteristic selective degeneration of ventrolateral nigral neurons seen in PD. This could explain some of the clinical differences between DLB and PD.
Subject(s)
Corpus Striatum/metabolism , Lewy Body Disease/metabolism , Membrane Glycoproteins/metabolism , Membrane Transport Proteins/metabolism , Nerve Tissue Proteins/metabolism , Parkinson Disease/metabolism , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/metabolism , Corpus Striatum/diagnostic imaging , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins , Functional Laterality , Humans , Lewy Body Disease/diagnosis , Lewy Body Disease/diagnostic imaging , Neurologic Examination , Occipital Lobe/diagnostic imaging , Occipital Lobe/metabolism , Parkinson Disease/diagnosis , Parkinson Disease/diagnostic imaging , Psychiatric Status Rating Scales , Putamen/diagnostic imaging , Putamen/metabolism , Severity of Illness Index , Striatonigral Degeneration/diagnostic imaging , Striatonigral Degeneration/metabolism , Tomography, Emission-Computed, Single-Photon , TropanesABSTRACT
BACKGROUND: Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40-70% loss of striatal dopamine. OBJECTIVE: To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life. METHODS: The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, (123)I-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method. RESULTS: Both DLB and PD patients had significantly lower uptake of radioactivity than patients with AD (p<0.001) and controls (p<0.001) in the caudate nucleus and the anterior and posterior putamen. CONCLUSION: FP-CIT SPET provides a means of distinguishing DLB from AD during life.
