Are cytochrome P4502D6 and apolipoprotein E genotypes associated with long-term cognitive and functional changes in patients treated with donepezil?

AIM: We investigated the associations of the single-nucleotide polymorphism rs1080985 of cytochrome P4502D6 (CYP2D6) and the apolipoprotein E (APOE) genotypes with cognitive and functional changes in patients treated with donepezil. METHODS: Sixty-five outpatients with Alzheimer's disease or mixed dementia being treated with donepezil were assessed at baseline and over 27 months. Changes in cognitive status, assessed with the Mini-Mental State Examination, and in functional status, assessed by the Activities of Daily Living Scale and the Instrumental Activities of Daily Living Scale, were evaluated as a function of CYP2D6 and APOE genotypes by using linear mixed models. Multiplicative interactions between the CYP2D6 and APOE genotypes and time were investigated. RESULTS: Individuals with the mutated CYP2D6 exhibited a slower decline in total Mini-Mental State Examination scores, orientation, registration, and functional status than those with the wild type. A significant interaction between CYP2D6, APOE, and time was found for changes in the Activities of Daily Living Scale; among the ε4 carriers, those with the mutated CYP2D6 exhibited a slower decline on the Activities of Daily Living Scale than those with the wild type. CONCLUSION: The CYP2D6 and APOE genotypes may modulate the effectiveness of donepezil on cognitive and functional status.

Longitudinal investigation of the role of cognitive reserve in the evolution of dementia in outpatients prescribed AChEI.

Aim: The role of cognitive reserve (CR) in modulating dementia has been broadly investigated. We aimed to evaluate the long-term effects of CR on cognitive functions in outpatients newly treated with acetylcholinesterase inhibitors.Method: Fifty older adults with dementia (age 80 ± 6.4 years) were followed up over 27 months. CR was assessed with the Cognitive Reserve Index questionnaire (CRIq), which provides a Total CR index and three proxy measures: Education, Working Activity and Leisure Time. The association between CR and cognition, evaluated by the Mini-Mental State Examination (MMSE), was tested through linear mixed models.Results: The cognitive profile of High CR individuals (n = 16) was more fluctuating than that of patients with Low CR (n = 34) up to 15 months of treatment, showingan alternation of improvements and worsening. At linear mixed models, CRIq Total score was significantly associated with MMSE over the follow-up either when considered as continuous (ß = 0.13 [95%CI:0.07-0.19], p < .001, per each 1-unit increase) orcategorical variable (ß = 3.62 [95%CI:1.77-5.47], p = .002, High vs Low CR). Among the CR domains, higher CRIq Leisure-time scores were significantly associated with higher MMSE during the follow-up (ß = 0.05 [95%CI:0.02-0.09], p = .009, per each 1-unit increase).Conclusion: The study indicates that higher CR, and especially Leisure Time-related CR, was associated with better cognitive performance in older outpatients with dementia treated with AChEI for 27 months. These findings suggest that Leisure Time-related CR could influence the evolution of dementia, and support the need of further investigations to verify the potential usefulness of interventions enhancing such domain even in advanced age.

Fibrinogen Levels and the Risk of Cerebrovascular Events in Older Adults With Both Depressive Symptoms and Cognitive Impairment: A Prospective Study.

Depression and cognitive impairment have been identified as risk factors for cerebrovascular events (CVE), and one of their potential etiological pathways is inflammatory status. This prospective study aims to investigate the association between inflammatory markers and the risk of CVE in a population of 2659 older adults, enrolled in the Progetto Veneto Anziani (Pro.V.A.), with depressive symptoms, cognitive impairment, or both conditions. For each individual, we assessed at baseline the presence of depressive symptoms (defined as a Geriatric Depression Scale ≥11), cognitive impairment (defined as a Mini-Mental State Examination <24), and serum levels of fibrinogen, white blood cells (WBC), and erythrocyte sedimentation rate (ESR). During a 4.4-year follow-up, 188 (7.1%) participants had CVE. Among the inflammatory markers, high fibrinogen values were associated with a 50% higher risk of CVE in the whole sample, and with a 4-fold higher risk in individuals with both depressive symptoms and cognitive impairment (hazard ratio = 4.04, 95% confidence interval: 1.45-11.23). Elevated WBC were associated with a 5% higher risk of CVE in the whole sample and in those with both conditions. No significant association was observed with the ESR. In conclusion, our study found that high fibrinogen levels may predict the risk of CVE in older people with concomitant depressive symptoms and cognitive impairment. Therefore, fibrinogen could be considered as an easily accessible aging biomarker, which might estimate the chronic inflammatory status and its potential detrimental effects on the most vulnerable older adults.

Effects of 21 months of cholinesterase inhibitors on cognitive and functional decline in demented patients.

AIMS: The aim of this study was to assess, in a natural setting, the development of cognitive, behavioral and functional performance of elderly dementia patients treated with cholinesterase inhibitors (ChEIs) during a 21-month follow-up. Another aim was to compare patterns of clinical changes in relation to patients' level of cognitive impairment at the beginning of therapy. METHOD: Of the 1987 elderly demented patients seen at our unit, 143 met the inclusion/ exclusion criteria, were followed for at least 21 months, and were thus included in the study. At baseline and each control point (up to 21 months), patients were scored for Mini Mental State Examination (MMSE), Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). RESULTS: After 21 months' treatment with ChEIs, patients showed a significant reduction in MMSE, ADL and IADL values. The MMSE score decreased by 1.7 points/year (95% CI -2.1; -1.3), irrespective of initial cognitive level, and was lower than that expected in non-treated patients (-3/-4 points/year). CONCLUSION: ChEI therapy is effective in slowing the progression of dementia, even in the long term, irrespective of baseline cognitive level.

The importance of sexual health in the elderly: breaking down barriers and taboos.

Aging-related physical changes do not necessarily lead to a decline in sexual functioning: good physical and mental health, a positive attitude toward sex in later life, and access to a healthy partner are associated with continued sexual activity, and regular sexual expression is associated with good physical and mental health. However, it is usually assumed that older adults do not have sexual desires, and elderly people often find it difficult to discuss this topic with their doctor. There are many potential barriers concerning sexuality in older age: the lack of a healthy sexual partner, depression, the monotony of a repetitive sexual relationship, a spouse's physical unattractiveness, hormone variability, and illness and/or iatrogenic factors. Adaptive coping strategies can considerably mitigate the impact of such factors, however, and one way of contributing to breaking down barriers and taboos is undoubtedly to ensure that physicians are willing to discuss their patients' sexual history. The aim of this review was to explore the barriers and taboos to sexual expression in seniors, to propose strategies to foster this aspect of their lives, and to help physicians investigate the sexual history of their elderly patients.

Nutritional and global indexes of progression in dementia: a 12-month prospective study.

BACKGROUND: To assess the influence of body mass index (BMI) on the progression of dementia. METHODS: Sixty elderly outpatients with untreated dementia followed for 12 months. All patients underwent clinical, cognitive, functional, and nutritional assessment at the baseline and after 12 months. Patients were divided into 2 groups by baseline BMI (< or ≥25 kg/m(2)). RESULTS: Participants with a baseline BMI ≥25 kg/m(2) had significantly higher Mini-Mental State Examination (MMSE) scores (21 ± 5.1 vs 15.9 ± 5.5; P < .001), while clinical dementia rating (CDR) and multidimensional prognostic index (MPI) scores were similar in the 2 groups. After 12 months, the MMSE score decreased significantly in both groups compared to the baseline, while the CDR and MPI scores increased significantly for patients with a baseline BMI <25 kg/m(2). CONCLUSION: A BMI cutoff of 25 kg/m(2) could be useful for identifying frail patients with dementia who will experience a more rapid global impairment, which could be assessed adequately using multidimensional evaluation tools.

An open-ended question: Alzheimer's disease and involuntary weight loss: which comes first?

BACKGROUND AND AIMS: After the onset of Alzheimer's disease (AD), a substantial percentage of patients experience involuntary weight loss (IWL), but there is some debate as to whether IWL is a cause or a consequence of AD. It may play a causal role, because nutritional deficiencies have been found to be associated with worsened cognitive performance, even in subjects without dementia. Conversely, it may be an effect of the disease, considering the hypothesis that the neurodegenerative process associated with AD may itself lead to IWL. The aim of the present review was to help to shed some light on the relationship between IWL and AD. METHODS: We focus on the problem of the relationship between AD and IWL, and on which comes first. RESULTS: Even when external factors are well controlled, the association between IWL and the progression of AD seems, for the time being, to be unavoidable. CONCLUSION: In the light of the literature on the topic, we conclude that IWL is more a consequence than a cause of AD, although chronic diseases and disabilities are factors that may facilitate cognitive decline and accelerate the onset of AD if they are not adequately treated from the nutritional standpoint.