Introduction Grip strength and walking pace have been linked to cognitive dysfunction. Their relationships, however, demand further clarification as the evidence is derived primarily from less‐comprehensive investigations. Methods A total of 340212 UK Biobank participants without dementia and cardiovascular diseases at baseline were analyzed. Cox proportional hazard models assessed the longitudinal associations. Results Over a mean follow‐up of 8.51 ± 2.68 years, 2424 incident dementia cases were documented. A 5 kg increment of absolute grip strength was associated with lower risks of all‐cause dementia (hazard ratio [HR] 0.857), Alzheimer's disease (HR 0.874), and vascular dementia (HR 0.788). The patterns of associations remained similar when grip strength was expressed in relative terms and quintiles. A slow walking pace demonstrated consistent associations with increased risks of all dementia types. Discussion Our findings provide amplified evidence and suggest that muscle fitness, reflected by objective grip strength measures and self‐reported walking pace, may be imperative for estimating the risks of dementia.
Background and purpose Circulating metabolites have been implicated in stroke pathogenesis, but their genetic determinants are understudied. Using a Mendelian randomization approach, our aim was to provide evidence for the relationship of circulating metabolites and the risk of stroke and its subtypes. Methods Genetic instruments of 102 circulating metabolites were obtained from a genome‐wide association study, including 24,925 European individuals. Stroke was extracted from the MEGASTROKE dataset (67,162 cases; 454,450 controls) and a lacunar stroke dataset (7338 cases; 254,798 controls). The magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury were evaluated by a genome‐wide association study of white matter hyperintensities (N = 18,381), fractional anisotropy (N = 17,663), mean diffusivity (N = 17,467) and brain microbleeds (N = 25,862). The inverse‐variance weighted method Mendelian randomization was used as the primary analytical method, and directional pleiotropy and heterogeneity were examined in sensitivity analyses. Results A genetic predisposition to a higher level of cholesterol in small and low‐density lipoprotein (LDL) was associated with risk of stroke (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.08–1.21, p = 5.98 × 10−7), especially for large‐artery atherosclerotic stroke (OR 1.34, 95% CI 1.19–1.52, p = 1.90 × 10−6). Total lipids in LDL particles were also associated with risk of stroke. A genetically determined higher cholesterol level in high‐density lipoprotein (HDL‐C) was associated with risk of intracerebral haemorrhage (OR 1.74, 95% CI 1.23–2.45, p = 1.66 × 10−3). No statistically significant association was found between genetic predisposition to circulating metabolites and magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury. Conclusions Genetically determined levels of lipids in small LDL were associated with the risk of stroke, suggesting that a therapeutic strategy targeting small LDL levels may be crucial for stroke prevention. HDL‐C was positively associated with the risk of intracerebral haemorrhage.
Background Neuropsychiatric symptoms (NPS) of dementia are a common issue in dementia patients. It generally presents as three disparate symptom clusters—agitation, psychosis, and mood disorders which have different biological and psychosocial triggers. Therefore, a “one size fits all” solution may not exist. Pharmacological treatments are its treatment of choice, but there is controversy about which agent should be used. We aimed to update and expand our previous work to compare and rank drugs for the treatment of neuropsychiatric symptoms of dementia. Methods We included all randomized controlled trials reported as double‐blind and comparing one active drug with another or with placebo. Studies searched Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, EMBASE, from database inception to Jun 28, 2019. Our primary outcome was change in overall neuropsychiatric symptoms measured with standardised rating scales. And the secondary outcomes were change in aggressive behavior, psychosis, apathy, and depressive symptoms. Effect size measures were standardised mean differences (SMD) with 95% credible intervals (CrIs). We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking probabilities. We conducted subgroup analyses to assess the robustness of our findings. Confidence in the evidence was assessed using CINeMA. The study protocol is registered with PROSPERO, number CRD42019132231. Results We identified 8175 citations and of these included 114 trials comprising nearly thirty thousand participants. Effect size estimates suggested galantamine was more effective than placebo for reducing overall neuropsychiatric symptoms. SMD compared with placebo for reduction of aggressive behavior found that aripiprazole and risperidone appeared to be more efficacious, citalopram and methylphenidate for reduction of apathy symptoms, memantine and donepezil for reduction of psychosis. While the certainty of evidence was low to very low. Conclusion This systematic review synthesized the available evidence on the comparative efficacy of different pharmacological approaches in the management of overall NPS, agitation, psychosis, apathy and depressive symptoms in dementia patients. These results may serve evidence‐based practice and inform patients, physicians, guideline developers. Especially, clinicians should differentiate these disparate symptom clusters since the appreciation of such complexity is vital to determine the appropriate treatment.
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