The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.

A higher rate of good response was observed in this study compared to that in previous investigations. The pharmacogenetic aspects do not seem to have an influence in the response.

Life expectancy in Brazil has increased markedly over the last 30 years. Hence, age-related disorders, such as Alzheimer's disease (AD), warrant special attention due to their high prevalence in the elderly. Pharmacologic treatment of AD is based on cholinesterase inhibitors (ChEI) and memantine, leading to modest clinical benefits both in the short and long-term. However, clinical response is heterogeneous and needs further investigation.OBJECTIVETo investigate the rate of response to ChEI in AD after three months of treatment.METHODSPatients with mild or moderate dementia due to probable AD or to AD associated with cerebrovascular disease were included in the study. The subjects were assessed at baseline and again after three months of ChEI treatment. Subjects were submitted to the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale, Katz Basic Activities of Daily Living, Pfeffer Functional Activities Questionnaire, Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Good response was defined by a gain of ≥2 points on the MMSE after three months of treatment in relation to baseline.RESULTSSeventy-one patients, 66 (93%) with probable AD and five (7%) with AD associated with cerebrovascular disease, were evaluated. The good response rate at three months was 31.0%, being 37.2% and 21.4% in mild and moderate dementia, respectively. There were no significant differences on most tests, except for improvement in hallucinations, agitation and dysphoria in moderate dementia patients.CONCLUSIONThe rate of good clinical response to ChEI was higher than usually reported. Specific behavioral features significantly improved in the subgroup of moderate dementia.

Background: Validation of cognitive instruments for detection of Alzheimer's disease (AD) based on correlation with diagnostic biomarkers allows more reliable identification of the disease. Objectives: To investigate the accuracy of the Brief Cognitive Screening Battery (BCSB) in the differential diagnosis between AD, non-AD cognitive impairment (both defined by cerebrospinal fluid [CSF] biomarkers) and healthy cognition, and to correlate CSF biomarker results with cognitive performance. Methods: Overall, 117 individuals were evaluated: 45 patients with mild cognitive impairment (MCI) or mild dementia within the AD continuum defined by the AT(N) classification [A+T+/-(N)+/]; 27 non-AD patients with MCI or mild dementia [A-T+/-(N)+/-]; and 45 cognitively healthy individuals without CSF biomarker results. All participants underwent evaluation using the BCSB. Results: The total BCSB and delayed recall (DR) scores of the BCSB memory test showed high diagnostic accuracy, as indicated by areas under the ROC curve (AUC): 0.89 and 0.87, respectively, for discrimination between AD and non-AD versus cognitively healthy controls. Similarly, total BCSB and DR displayed high accuracy (AUC-ROC curves of 0.89 and 0.91, respectively) for differentiation between AD and controls. BCSB tests displayed low accuracy for differentiation between AD and non-AD. The CSF levels of biomarkers correlated significantly, though weakly, with DR. Conclusions: Total BCSB and DR scores presented good accuracy for differentiation between patients with a biological AD diagnosis and cognitively healthy individuals, but low accuracy for differentiating AD from non-AD patients.

Background: The National Institute on Aging and Alzheimer’s Association (NIA-AA) proposed the AT(N) model to diagnose Alzheimer’s disease (AD) considering some biomarkers: amyloid beta (A), phosphorylated tau (T), and neurodegeneration (N). Still, AT(N) correlation with cognitive markers is not yet covered. Objective: To investigate the neuropsychological profile of patients with CSF biomarkers according to AT(N) classification. Methods: Sixty-five patients with thorough neuropsychological data and results of CSF biomarkers were included in the study. We performed a cluster analysis using biomarkers results. The validity was checked by neuropsychological tests scores. Results: We found three clusters: Cluster 1 (n=24), classified as non-AD; Clusters 2 (n=9) and 3 (n=32), classified as AD. Cluster 2 had a higher burden of phosphorylated tau and total tau. All groups were similar regarding sociodemographics and functionality. AD groups had worse memory deficits than the non-AD cluster, but Cluster 2 was more affected than Cluster 3. No other cognitive difference was found, except in the Cubes subtest (Cluster 3>Cluster 2).Conclusion: Memory was the sole domain able to discriminate AD from non-AD, probably due to Cluster 1 heterogeneity. Further studies are warranted to explore this hypothesis. A smaller cluster with AD shows variability in the biomarker profile, which is relevant given its worse cognitive scores.