Neurocognitive disorders, particularly in older adults, significantly affect functional abilities and global health. Physical activity has emerged as a potential non-pharmacological intervention to improve cognitive performance in patients with neurodegenerative diseases. This review specifically addressed the issue of tailored physical activity interventions for individuals with various neurocognitive disorders. This literature review analyzed studies investigating the effects of physical activity on cognitive function in patients with Alzheimer's disease (AD), vascular cognitive impairment, Parkinson's disease, and Lewy body dementia. The studies were evaluated for methodological rigor, participant characteristics, types of physical activities, and cognitive outcomes. Of the 21 studies reviewed, 14 reported beneficial effects of physical exercise on cognitive function, particularly with aerobic activities. While most studies observed improvements in cognitive performance and physical functional capacity, results were inconsistent, and effect sizes were modest. Mechanisms proposed for cognitive improvement in AD included reductions in β-amyloid and tau protein burdens, improved glucose metabolism, and enhanced brain-derived neurotrophic factor levels. Specific improvements were noted in Parkinson's disease, with evidence suggesting mediation through dopamine pathways. Despite evidence of short-term benefits, significant variability exists among studies, highlighting the need for individualized exercise programs tailored to specific neurocognitive conditions. Physical activity stands as a cornerstone non-pharmacological intervention, essential for supporting cognitive health in individuals with neurodegenerative diseases. Further research is necessary to establish long-term effects and optimal exercise modalities, along with standardized evaluation criteria to assess the cognitive impacts of physical activity reliably.

The use of cerebrospinal (CSF) biomarkers in the diagnosis of Alzheimer's disease (AD) has been gaining interest in clinical practice. Although their usefulness has been demonstrated, their potential value in older patients remains debated. To assess whether knowledge of the results of CSF AD biomarkers was associated with the same gain in diagnostic confidence in older adults > 80 than in younger patients. Prospective multicenter study, including memory clinics physicians who completed a two-part questionnaire for all their patients addressing the requirement for assessment of Alzheimer's disease biomarkers in CSF proposed as part of routine care during the study period. 30 secondary or tertiary memory clinics in France. Clinicians indicated their diagnosis hypothesis and an estimate of their diagnostic confidence [scale 1-10]. Receiver operating characteristic (ROC) analysis, including the calculation of the area under the curve (AUC), was conducted using logistic regression to evaluate the diagnostic performance of CSF AD biomarkers. In 813 consecutive patients, median age 70 [interquartile range (IQR) = 63 - 77] including 132 patients over 80 years, we observed a similar confidence gain in CSF biomarkers between older and younger patients, both for AD and non-AD diagnoses. In older patients, the added value of CSF biomarkers was greater when CSF biomarkers indicated AD profile whereas the initial hypothesis was "non-AD", leading to a final diagnosis of AD (2.4 ± 1.6 versus 1.1 ± 2.1, p-value, p = 0.03). ROC analyses showed similar performance of AD CSF biomarkers in older and younger patients. CSF AD biomarkers added substantial value to clinical assessment in patients over 80. Their use seems crucial in the diagnostic process for older adults referred to memory clinics.

Purpose: Polypharmacy is a frequent situation in older adults that increases the risk of drug-drug interactions (DDIs), both pharmacokinetic (PK) and pharmacodynamic (PD). Direct oral anticoagulants (DOACs) are frequently prescribed in older adults, mainly because of the high prevalence of atrial fibrillation (AF). DOACs are subject to cytochrome P450 3A4 (CYP3A4)- and/or P-glycoprotein (P-gp)-mediated PK DDIs and PD DDIs when co-administered with drugs that interfere with platelet function. The aim of our study was to assess the prevalence of DDIs involving DOACs in older adults and the associated risk factors at admission and discharge. Methods: This was a cross-sectional study conducted in an acute geriatric unit between January 1, 2018 and December 31, 2022, including patients over 75 years of age treated with DOACs at admission and/or discharge, for whom a comprehensive collection of co-medications was performed. Results: From 909 hospitalizations collected, the prevalence of PK DDIs involving DOACs was 16.9% at admission and 20.7% at discharge, and the prevalence of PD DDIs was 20.7% at admission and 20.2% at discharge. Factors associated with DDIs were bleeding history [adjusted odds ratio (ORa) 1.74, 95% confidence interval (CI) 1.13–2.68], number of drugs > 6 (ORa 2.54, 95% CI 1.88–3.46) and reduced dose of DOACs (ORa 0.39, 95% CI 0.28–0.54) at admission and age > 87 years (ORa 0.74, 95% CI 0.55–0.99), number of drugs > 6 (ORa 2.01, 95% CI 1.48–2.72) and reduced dose of DOACs (ORa 0.41, 95% CI 0.30–0.57) at discharge. Conclusion: This study provides an indication of the prevalence of DDIs as well as the profile of DDIs and patients treated with DOACs.

Hyperhomocysteinemia (HHcy) is an established risk factor for cognitive impairment. The specific role of HHcy in the pathophysiology of Alzheimer's disease (AD) is debated, as most of the suspected mechanisms overlap with those of vascular dementia (VD). The aim of this study was to explore the association between plasma homocysteine (Hcy) levels and cerebrospinal fluid (CSF) biomarkers of AD, as well as brain magnetic resonance imaging (MRI) features. Cross-sectional observational analysis from a single-center tertiary memory clinic. We first assessed the association between Hcy in tertiles and the CSF AD biomarkers (according to the Amyloid (A) Tau (T) Neurodegeneration (N) classification) with further adjustments for age and sex. Then, we analyzed the relationship between HHcy and hippocampal atrophy (Scheltens scale) and white matter lesions (WML) (Fazekas scale) on brain MRI. We included 507 patients [mean age 68.9 (standard deviation=8.9)] with mean plasma Hcy at 13.3 (4.7) µmol/L in this study. There was no significant association between Hcy tertiles and CSF AD biomarkers. Plasma Hcy levels showed no correlation with any CSF AD biomarkers. The severity of WML increased with higher Hcy tertiles (p<0.0001). Patients with a CSF AD (A+T+) profile exhibited elevated mean Hcy levels when they presented moderate to severe WML (p<0.0001). Our findings challenge the link between Hcy and AD pathophysiology while highlighting a significant connection between Hcy and microvascular cognitive impairment. Further longitudinal studies are needed to validate these conclusions.