Background: This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia. Method: Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGI-C) scales. Results: A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean ± SE dose of risperidone was 0.95 ± 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p < .001). A similar improvement was also seen for the CMAI total non-aggression subscale (p < .002) and for the BEHAVE-AD total (p < .001) and psychotic symptoms subscale (p = .004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p < .001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups. Conclusion: Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.

Aims/hypothesis The aim was to investigate the relationship between severe hypoglycaemia and cognitive impairment in older patients with diabetes. Methods A sample of 302 diabetic patients aged ≥70 years was assessed for dementia or cognitive impairment without dementia in 2001-2002 and a subsample of non-demented patients (n=205) was followed to assess cognitive decline. A history of severe hypoglycaemia was determined from self-reports, physician assessments and records of health service use for hypoglycaemia (HSH). Prospective HSH was determined up to 2006. Data analysis, including multiple logistic and Cox regression models, was used to determine whether: (1) there were cross-sectional associations between hypoglycaemia and cognitive status, (2) historical hypoglycaemia predicted cognitive decline, and (3) baseline cognitive status predicted subsequent HSH.Results There were significant cross-sectional associations between both cognitive impairment and dementia and hypoglycaemia. Independent risk factors for future HSH included dementia (hazard ratio 3.00, 95% CI 1.06-8.48) and inability to self-manage medications (hazard ratio 4.17, 95% CI 1.43-12.13). However, there were no significant associations between historical hypoglycaemia, incident HSH and cognitive decline. Conclusions/interpretation Dementia is an important risk factor for hypoglycaemia requiring health service utilisation. We found no evidence that hypoglycaemia contributes to cognitive impairment in older patients with diabetes.

Aims/hypothesis Diabetes is associated with an increased risk of dementia but the reasons for this association are unclear because there are many potential mechanisms. We explored the relative contribution of diabetes-related variables as predictors of dementia in older individuals with diabetes. Methods Survivors, aged ≥70 or more, were recruited from an existing observational cohort study 7.6±1.0 years after baseline, when they underwent a comprehensive assessment of diabetes, complications and cardiovascular risk factors. Dementia, probable Alzheimer's disease and cognitive impairment without dementia were diagnosed clinically. Logistic regression modelling determined independent predictors of cognitive diagnoses. Results Of 302 participants, aged 75.7±4.6 years, 28 (9.3%) had dementia (16 with probable Alzheimer's disease) and 60 (19.9%) had cognitive impairment without dementia. The major independent longitudinal predictors of dementia were older age (per decade; odds ratio 4.0, 95% CI 1.59-10.10), diabetes duration (for each 5 years; odds ratio 1.69, 95% CI 1.24-2.32), peripheral arterial disease (odds ratio 5.35, 95% CI 2.08-13.72) and exercise (which was protective; odds ratio 0.26, 95% CI 0.09-0.73). For Alzheimer's disease, diabetes duration was an independent predictor in addition to age and diastolic blood pressure. The results of the cross-sectional analyses were similar with respect to diabetes duration and peripheral arterial disease. Conclusions/interpretation Peripheral arterial disease is a strong independent risk factor for dementia in diabetes. After adjustment for a wide range of potential risk factors, diabetes duration remains independently associated with dementia and probable Alzheimer's disease, indicating that factors not measured in this study may be important in the pathogenesis of dementia in diabetes.

This study provides Class I evidence that vitamin supplementation with daily doses of 500 μg [DOSAGE ERROR CORRECTED] of B(12), 2 mg of folic acid, and 25 mg of B(6) over 2 years does not improve cognitive function in hypertensive men aged 75 and older.

OBJECTIVE -The purpose of this study was to determine longitudinal predictors of cognitive decline in older individuals with diabetes who did not have dementia.RESEARCH DESIGN AND METHODS -Cognitive assessments were performed in 205 subjects with diabetes (mean age 75.3 years) and repeated a median 1.6 years later. The sample was drawn from an existing cohort study, and data on diabetes, cardiovascular risk factors, and complications were collected 7.6 Ϯ 1.1 years before and at the time of the initial cognitive assessment. Cognitive status was defined using the Clinical Dementia Rating (CDR) scale, and cognitive decline was defined by change in CDR.RESULTS -The sample included 164 subjects with normal cognition (CDR 0) and 41 with cognitive impairment without dementia (CDR 0.5). At follow-up, 33 (16.1%) had experienced cognitive decline (4 new cases of dementia and 29 cognitive impairment without dementia). Only educational attainment predicted cognitive decline from the data collected 7.6 years before cognitive assessment. Univariate predictors of cognitive decline at the time of the first cognitive assessment included age, education, urinary albumin-to-creatinine ratio (ACR), and treatment with either ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). With multiple logistic regression controlling for age and education, cognitive decline was predicted by natural logarithm ACR (odds ratio 1.37 [95% CI 1.05-1.78], P ϭ 0.021), whereas treatment with either ACEIs or ARBs was protective (0.28 [0.12-0.65], P ϭ 0.003).CONCLUSIONS -In this sample of older patients with diabetes, microalbuminuria was a risk factor for cognitive decline, whereas drugs that inhibit the renin-angiotensin system were protective. These observations require confirmation because of their considerable potential clinical implications.