Purpose of the study To examine the effect of late-life body mass index (BMI) and rapid weight loss on incident mild cognitive impairment (MCI) and Alzheimer’s disease (AD) Design Prospective longitudinal cohort study Setting National Alzheimer’s Coordinating Center (NACC) Uniform Data Set, including 34 past and current National Institute on Aging-funded AD Centers across the United States Participants 6940 older adults (n=5061 normal cognition (NC); n=1879 MCI) Measurements BMI (kg/m2) and modified Framingham Stroke Risk Profile (FSRP) score (sex, age, systolic blood pressure, anti-hypertension medication, diabetes mellitus, cigarette smoking, prevalent cardiovascular disease, atrial fibrillation) were assessed at baseline. Cognition and weight were assessed annually. Results Multivariable binary logistic regression, adjusting for age, sex, race, education, length of follow-up, and modified FSRP related late-life BMI to risk of diagnostic conversion from NC to MCI or AD and from MCI to AD. Secondary analyses related late-life BMI to diagnostic conversion in the presence of rapid weight loss (>5% decrease in 12 months) and apolipoprotein E (APOE) ε4. During a mean 3.8-year follow-up period, 12% of NC participants converted to MCI or AD and 49% of MCI participants converted to AD. Higher baseline BMI was associated with a reduced probability of diagnostic conversion, such that for each one-unit increase in baseline BMI there was a reduction in diagnostic conversion for both NC (OR=0.977, 95%CI 0.958–0.996, p=0.015) and MCI participants (OR=0.962, 95%CI 0.942–0.983, p<0.001). The protective effect of higher baseline BMI did not persist in the setting of rapid weight loss but did persist when adjusting for APOE. Conclusions Higher late-life BMI is associated with a lower risk of incident MCI and AD but is not protective in the presence of rapid weight loss.

BackgroundA better understanding of the optimal “dose” of behavioral interventions to affect change in weight-related outcomes is a critical topic for childhood obesity intervention research. The objective of this review was to quantify the relationship between dose and outcome in behavioral trials targeting childhood obesity to guide future intervention development.MethodsA systematic review and meta-regression included randomized controlled trials published between 1990 and June 2017 that tested a behavioral intervention for obesity among children 2–18 years old. Searches were conducted among PubMed (Web-based), Cumulative Index to Nursing and Allied Health Literature (EBSCO platform), PsycINFO (Ovid platform) and EMBASE (Ovid Platform). Two coders independently reviewed and abstracted each included study. Dose was extracted as intended intervention duration, number of sessions, and length of sessions. Standardized effect sizes were calculated from change in weight-related outcome (e.g., BMI-Z score).ResultsOf the 258 studies identified, 133 had sufficient data to be included in the meta-regression. Average intended total contact (# sessions x length of sessions) was 27.7 (SD 32.2) hours and average duration was 26.0 (SD 23.4) weeks. When controlling for study covariates, a random-effects meta-regression revealed no significant association between contact hours, intended duration or their interaction and effect size.ConclusionsThis systematic review identified wide variation in the dose of behavioral interventions to prevent and treat pediatric obesity, but was unable to detect a clear relationship between dose and weight-related outcomes. There is insufficient evidence to provide quantitative guidance for future intervention development. One limitation of this review was the ability to uniformly quantify dose due to a wide range of reporting strategies. Future trials should report dose intended, delivered, and received to facilitate quantitative evaluation of optimal dose.Trial registrationsThe protocol was registered on PROSPERO (Registration #CRD42016036124).Electronic supplementary materialThe online version of this article (10.1186/s12966-017-0615-7) contains supplementary material, which is available to authorized users.

SummaryObjectiveThere are conflicting data regarding the association between body mass index (BMI) and health‐related quality of life (HRQoL), especially among certain population subgroups and for mental and physical health domains.MethodsThis study analysed the relationship between BMI and HRQoL (Patient‐Reported Outcomes Measurement Information System mental and physical health scales) using ordinary least squares regression. Each model allowed for the possibility of a non‐linear relationship between BMI and the outcome, adjusting for age, gender, comorbidities, diet and physical activity.ResultsA total of 10,133 respondents were predominantly female (71.7%), White (84.1%), median age of 52.1 years (interquartile range 37.2–63.3) and median BMI of 27.9 (interquartile range 24.0–33.2). In adjusted models, BMI was significantly associated with physical and mental HRQoL (p < 0.001). For physical HRQoL, there was a significant interaction with age (p = 0.02). For mental HRQoL, there was a significant interaction with sex (p = 0.0004) but not age (p = 0.7).ConclusionsThis study demonstrates a non‐linear association of variable clinical relevance between BMI and HRQoL after adjusting for demographic factors and comorbidities. The relationship between BMI and HRQoL is nuanced and impacted by gender and age. These findings challenge the idea of obesity as a main driver of reduced HRQoL, particularly among women and with respect to mental HRQoL.

White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of β-amyloid42 deposition (Aβ42), hyperphosphorylated tau pathology (p-tau), neurodegeneration (total tau), and axonal injury (neurofilament light; NFL) in relation to log-transformed WMHs volume. Participants free of clinical stroke and dementia were drawn from the Vanderbilt Memory & Aging Project (n=148, 72±6 years). Linear regression models adjusted for age, sex, race/ethnicity, education, intracranial volume, modified Framingham Stroke Risk Profile (excluding points assigned for age), cognitive diagnosis, and APOE-ε4 carrier status. Aβ42 (β=−0.001, p=0.007) and NFL (β=0.0003, p=0.01) concentrations related to WMHs, but neither p-tau nor total tau associations with WMHs reached statistical significance (p-values>0.21). In a combined model, NFL accounted for 3.2% of unique variance in WMHs and Aβ42 accounted for an additional 4.3% beyond NFL, providing novel evidence of the co-occurrence of at least two distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury.

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