Silent brain infarcts and the risk of dementia and cognitive decline

BACKGROUND: Silent brain infarcts are frequently seen on magnetic resonance imaging (MRI) in healthy elderly people and may be associated with dementia and cognitive decline. METHODS: We studied the association between silent brain infarcts and the risk of dementia and cognitive decline in 1015 participants of the prospective, population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia and stroke at base line. Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period. We performed Cox proportional-hazards and multiple linear-regression analyses, adjusted for age, sex, and level of education and for the presence or absence of subcortical atrophy and white-matter lesions. RESULTS: During 3697 person-years of follow-up (mean per person, 3.6 years), dementia developed in 30 of the 1015 participants. The presence of silent brain infarcts at base line more than doubled the risk of dementia (hazard ratio, 2.26; 95 percent confidence interval, 1.09 to 4.70). The presence of silent brain infarcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function. Silent thalamic infarcts were associated with a decline in memory performance, and nonthalamic infarcts with a decline in psychomotor speed. When participants with silent brain infarcts at base line were subdivided into those with and those without additional infarcts at follow-up, the decline in cognitive function was restricted to those with additional silent infarcts. CONCLUSIONS: Elderly people with silent brain infarcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions

Alcohol intake in relation to brain magnetic resonance imaging findings in older persons without dementia

BACKGROUND: Consumers of light-to-moderate amounts of alcohol have a lower risk of dementia and, possibly, Alzheimer disease than do abstainers. Because vascular disease may contribute to symptoms of Alzheimer disease, reduction of cerebrovascular disease in consumers of light amounts of alcohol could account for that observation. However, a low concentration of alcohol may also have direct effects on the hippocampus, a brain structure highly affected by Alzheimer disease. OBJECTIVE: We investigated alcohol intake in relation to brain magnetic resonance imaging (MRI) findings of presumed vascular

Diversity in Alzheimer\u27s Disease Drug Trials: The Importance of Eligibility Criteria

INTRODUCTION: To generalize safety and efficacy findings, it is essential that diverse populations are well represented in Alzheimer\u27s disease (AD) drug trials. In this review, we aimed to investigate participant diversity in disease-modifying AD trials over time, and the frequencies of participant eligibility criteria. METHODS: A systematic review was performed using Medline, Embase, the Cochrane Library, and Clinicaltrials.gov, identifying 2247 records. RESULTS: In the 101 included AD trials, participants were predominantly White (median percentage: 94.7%, interquartile range: 81.0-96.7%); and this percentage showed no significant increase or decrease over time (2001-2019). Eligibility criteria such as exclusion of persons with psychiatric illness (78.2%), cardiovascular disease (71.3%) and cerebrovascular disease (68.3%), obligated caregiver attendance (80.2%), and specific Mini-Mental State Examination scores (90.1%; no significant increase/decrease over time) may have led to a disproportionate exclusion of ethnoracially diverse individuals. DISCUSSION: Ethnoracially diverse participants continue to be underrepresented in AD clinical trials. Several recommendations are provided to broaden eligibility criteria

Application of ultrasound to monitor in vivo residual bone movement within transtibial prosthetic sockets

Transtibial prosthetic users do often struggle to achieve an optimal prosthetic fit, leading to residual limb pain and stump-socket instability. Prosthetists face challenges in objectively assessing the impact of prosthetic adjustments on residual limb loading. Understanding the mechanical behaviour of the pseudo-joint formed by the residual bone and prosthesis may facilitate prosthetic adjustments and achieving optimal fit. This study aimed to assess the feasibility of using B-mode ultrasound to monitor in vivo residual bone movement within a transtibial prosthetic socket during different stepping tasks. Five transtibial prosthesis users participated, and ultrasound images were captured using a Samsung HM70A system during five dynamic conditions. Bone movement relative to the socket was quantified by tracking the bone contour using Adobe After-Effect. During the study a methodological adjustment was made to improve data quality, and the first two participants were excluded from analysis. The remaining three participants exhibited consistent range of motion, with a signal to noise ratio ranging from 1.12 to 2.59. Medial–lateral and anterior–posterior absolute range of motion varied between 0.03 to 0.88 cm and 0.14 to 0.87 cm, respectively. This study demonstrated that it is feasible to use B-mode ultrasound to monitor in vivo residual bone movement inside an intact prosthetic socket during stepping tasks

Subjective cognitive decline and self-reported sleep problems: The SCIENCe project

We aim to investigate the frequency and type of sleep problems in memory clinic patients with subjective cognitive decline (SCD) and their association with cognition, mental health, brain magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) biomarkers. Three hundred eight subjects (65 ± 8 years, 44% female) were selected from the Subjective Cognitive Impairment Cohort (SCIENCe) project. All subjects answered two sleep questionnaires, Berlin Questionnaire (sleep apnea) and Pittsburgh Sleep Quality Index (sleep quality) and underwent a standardized memory clinic work-up. One hundred ninety-eight (64%) subjects reported sleep problems, based on 107 (35%) positive screenings on sleep apnea and 162 (53%) on poor sleep quality. Subjects with sleep problems reported more severe depressive symptoms, more anxiety, and more severe SCD. Cognitive tests, MRI, and CSF biomarkers did not differ between groups. Our results suggest that improvement of sleep quality and behaviors are potential leads for treatment in many subjects with SCD to relieve the experienced cognitive complaints

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition

Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy: Collaborative Analysis of 21 European Cohort Studies.

BACKGROUND:  Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European observational HIV cohorts. METHODS:  We included HIV-positive adults starting cART after 1 January 1996. We analyzed incidence rates and risk factors for developing KS up to 90 and 180 days and 1, 2, 5, and 8 years after cART start and fitted univariable and multivariable Cox regression models. RESULTS:  We included 109 461 patients from 21 prospective clinical cohorts in Europe with 916 incident KS cases. The incidence rate per 100 000 person-years was highest 6 months after starting cART, at 953 (95% confidence interval, 866-1048), declining to 82 (68-100) after 5-8 years. In multivariable analyses adjusted for exposure group, origin, age, type of first-line regimen, and calendar year, low current CD4 cell counts increased the risk of developing KS throughout all observation periods after cART initiation. Lack of viral control was not associated with the hazard of developing KS in the first year after cART initiation, but was over time since starting cART increasingly positively associated (P < .001 for interaction). CONCLUSION:  In patients initiating cART, both incidence and risk factors for KS change with time since starting cART. Whereas soon after starting cART low CD4 cell count is the dominant risk factor, detectable HIV-1 RNA viral load becomes an increasingly important risk factor in patients who started cART several years earlier, independently of immunodeficiency