Context Some evidence suggests that treating vascular risk factors and performing mentally stimulating activities may delay cognitive impairment onset in older adults. Exposure to a complex ...neighborhood environment may be one mechanism to help delay cognitive decline. Evidence acquisition PubMed, Web of Science, and ProQuest Dissertation and Theses Global database were systematically reviewed, identifying 25 studies published from February 1, 1989 to March 5, 2016 (data synthesized, May 3, 2015 to October 7, 2016). The review was restricted to quantitative studies focused on: (1) neighborhood social and built environment and cognition; and (2) community-dwelling adults aged ≥45 years. Evidence synthesis The majority of studies were cross-sectional, U.S.-based, and found at least one significant association. The diversity of measures and neighborhood definitions limited the synthesis of findings in many instances. Evidence was moderately strong for an association between neighborhood SES and cognition, and modest for associations between neighborhood demographics, design, and destination accessibility and cognition. Most studies examining effect modification found significant associations, with some evidence for effect modification of the neighborhood SES−cognition association by individual-level SES. No studies had low risk of bias and many tested multiple associations that increased the chance of a statistically significant finding. Considering the studies to date, the evidence for an association between neighborhood characteristics and cognition is modest. Conclusions Future studies should include longitudinal measures of neighborhood characteristics and cognition; examine potential effect modifiers, such as sex and disability; and study mediators that may help elucidate the biological mechanisms linking neighborhood environment and cognition.
Summary Background Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and ...pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies. Methods In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of tau neurofibrillary tangles, neuritic plaques, α-synuclein inclusions, and other pathological changes in cortical regions. These samples were graded on an ordinal scale and genotyped for variants associated with synucleinopathies. We assessed the interval from onset of motor symptoms to onset of dementia, and overall survival in groups with varying levels of comorbid Alzheimer's disease pathology according to US National Institute on Aging–Alzheimer's Association neuropathological criteria, and used multivariate regression to control for age at death and sex. Findings On the basis of data from 213 patients who had been followed up to autopsy and met inclusion criteria of Lewy body disorder with autopsy-confirmed α synucleinopathy, we identified 49 (23%) patients with no Alzheimer's disease neuropathology, 56 (26%) with low-level Alzheimer's disease neuropathology, 45 (21%) with intermediate-level Alzheimer's disease neuropathology, and 63 (30%) with high-level Alzheimer's disease neuropathology. As levels of Alzheimer's disease neuropathology increased, cerebral α-synuclein scores were higher, and the interval between onset of motor and dementia symptoms and disease duration was shorter (p<0·0001 for all comparisons). Multivariate regression showed independent negative associations of cerebral tau neurofibrillary tangles score with the interval between onset of motor and dementia symptoms (β −4·0, 95% CI −5·5 to −2·6; p<0·0001; R2 0·22, p<0·0001) and with survival (–2·0, −3·2 to −0·8; 0·003; 0·15, <0·0001) in models that included age at death, sex, cerebral neuritic plaque scores, cerebral α-synuclein scores, presence of cerebrovascular disease, MAPT haplotype, and APOE genotype as covariates. Interpretation Alzheimer's disease neuropathology is common in synucleinopathies and confers a worse prognosis for each increasing level of neuropathological change. Cerebral neurofibrillary tangles burden, in addition to α-synuclein pathology and amyloid plaque pathology, are the strongest pathological predictors of a shorter interval between onset of motor and dementia symptoms and survival. Diagnostic criteria based on reliable biomarkers for Alzheimer's disease neuropathology in synucleinopathies should help to identify the most appropriate patients for clinical trials of emerging therapies targeting tau, amyloid-β or α synuclein, and to stratify them by level of Alzheimer's disease neuropathology. Funding US National Institutes of Health (National Institute on Aging and National Institute of Neurological Disorders and Stroke).
CLINICAL INVESTIGATIONS Ge Li, MD, PhD; Isaac C. Rhew, MPH; Jane B. Shofer, MS ...
Journal of the American Geriatrics Society (JAGS),
08/2007, Letnik:
55, Številka:
8
Journal Article
Recenzirano
To assess variation in the association between blood pressure (BP) and risk for dementia across a spectrum of older ages and to examine BP changes before dementia onset. Prospective cohort study. A ...large health maintenance organization in Seattle, Washington. A cohort of 2,356 members of a large health maintenance organization aged 65 and older who were initially without dementia. Dementia diagnosis was assessed biennially, and systolic (SBP) and diastolic BP (DBP) were measured at baseline and at four follow-up assessments. Cox proportional hazards models were used to estimate hazard ratios (HRs) for dementia and Alzheimer's disease (AD) associated with baseline BP in different age groups. Within the youngest age group (65-74 at enrollment) a greater risk for dementia was found in participants with high SBP (160 mmHg) (hazard ratio (HR)=1.60, 95% confidence interval (CI)=1.01-2.55) or borderline-high DBP (80-89 mmHg) (HR=1.59, 95% CI=1.07-2.35) than for those with normal BP (SBP <140 mmHg and DBP <80 mmHg). The dementia risk associated with SBP declined with increasing age (SBP-by-age interaction, P =.01). SBP declined similarly with aging in subjects who developed dementia and those who did not. Thus, in this sample, the association between SBP and dementia risk was not dependent on when BP was measured in relation to onset of dementia. High SBP was associated with greater risk of dementia in the young elderly (<75) but not in older subjects. Adequate control of hypertension in early old age may reduce the risk for dementia. PUBLICATION ABSTRACT
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