A randomized feasibility trial of the modified Atkins diet in older adults with mild cognitive impairment due to Alzheimer's disease.

Background: Alzheimer's disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory in persons with mild cognitive impairment due to early AD and explores potential mechanisms of action. Methods: We conducted a 12-week, parallel-group, controlled feasibility trial of a ketogenic diet, the modified Atkins diet (MAD), compared to a control diet in patients with cognitive impairments attributed to AD. We administered neuropsychological assessments, including memory tests, and collected blood samples at baseline and after 12 weeks of intervention. We performed untargeted lipidomic and targeted metabolomic analyses on plasma samples to detect changes over time. Results: A total of 839 individuals were screened to yield 38 randomized participants, with 20 assigned to receive MAD and 18 assigned to receive a control diet. Due to attrition, only 13 in the MAD arm and nine in the control arm were assessed for the primary endpoint, with two participants meeting ketosis levels used to define MAD adherence criteria. The average change from baseline in the Memory Composite Score was 1.37 (95% CI: -0.87, 4.90) points higher in the MAD group compared to the control group. The effect size of the intervention on baseline MAD change was moderate (Cohen's D = 0.57, 95% CI: -0.67, 1.33). In the 15 participants (nine MAD, six control) assessed for lipidomic and metabolomic-lipidomics and metabolomics, 13 metabolites and 10 lipids showed significant changes from baseline to 12 weeks, including triacylglycerols (TAGs, 50:5, 52:5, and 52:6), sphingomyelins (SM, 44:3, 46:0, 46:3, and 48:1), acetoacetate, fatty acylcarnitines, glycerol-3-phosphate, and hydroxy fatty acids. Conclusions: Attrition was greatest between baseline and week 6. All participants retained at week 6 completed the study. Despite low rates of adherence by criteria defined a priori, lipidomic and metabolomic analyses indicate significant changes from baseline in circulating lipids and metabolites between MAD and control participants at 12-week postrandomization, and MAD participants showed greater, albeit nonsignificant, improvement in memory.

Hearing Impairment and Physical Activity and Physical Functioning in Older Adults: Baseline Results From the ACHIEVE Trial.

BACKGROUND: Hearing loss is associated with restricted physical activity (PA) and impaired physical functioning, yet the relationship between severity of hearing impairment (HI) and novel PA measures in older adults with untreated HI is not well understood. METHODS: Analyses included 845 participants aged ≥70 years (mean = 76.6 years) with a better-hearing ear pure-tone average (PTA) ≥30 and <70 dB in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study who wore an ActiGraph accelerometer for 7 days. Physical functioning measures included grip strength and the Short Physical Performance Battery (SPPB). Linear regression models estimated the association by HI level (moderate or greater [PTA ≥ 40 dB] vs mild [PTA < 40 dB]) and continuous hearing with total daily activity counts, active minutes/day, activity fragmentation, grip strength, and gait speed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of poor performance on the SPPB (≤6) and its subtests (≤2). Mixed-effects models estimated differences by HI level in activity by time of day. RESULTS: Participants with moderate or greater HI had poorer physical functioning, particularly balance (OR = 2.17, 95% CI = 1.29-3.67), versus those with mild impairment. There was no association of HI level with activity quantities or fragmentation. For diurnal patterns of activity, participants with moderate or greater HI had fewer activity counts in the afternoon (12:00 pm -05:59 pm). CONCLUSIONS: Older adults with worse hearing had shifted diurnal patterns and poorer balance performance. Exercise programs should be tailored to older adults with different levels of HI to maintain PA and physical functioning, particularly balance control.

Description of the Baseline Audiologic Characteristics of the Participants Enrolled in the Aging and Cognitive Health Evaluation in Elders Study.

PURPOSE: The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a randomized clinical trial designed to determine the effects of a best-practice hearing intervention versus a successful aging health education control intervention on cognitive decline among community-dwelling older adults with untreated mild-to-moderate hearing loss. We describe the baseline audiologic characteristics of the ACHIEVE participants. METHOD: Participants aged 70-84 years (N = 977; Mage = 76.8) were enrolled at four U.S. sites through two recruitment routes: (a) an ongoing longitudinal study and (b) de novo through the community. Participants underwent diagnostic evaluation including otoscopy, tympanometry, pure-tone and speech audiometry, speech-in-noise testing, and provided self-reported hearing abilities. Baseline characteristics are reported as frequencies (percentages) for categorical variables or medians (interquartiles, Q1-Q3) for continuous variables. Between-groups comparisons were conducted using chi-square tests for categorical variables or Kruskal-Wallis test for continuous variables. Spearman correlations assessed relationships between measured hearing function and self-reported hearing handicap. RESULTS: The median four-frequency pure-tone average of the better ear was 39 dB HL, and the median speech-in-noise performance was a 6-dB SNR loss, indicating mild speech-in-noise difficulty. No clinically meaningful differences were found across sites. Significant differences in subjective measures were found for recruitment route. Expected correlations between hearing measurements and self-reported handicap were found. CONCLUSIONS: The extensive baseline audiologic characteristics reported here will inform future analyses examining associations between hearing loss and cognitive decline. The final ACHIEVE data set will be publicly available for use among the scientific community. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24756948.

Hearing loss and risk of depressive symptoms in older adults in the Health ABC study.

Objective: Hearing loss (HL) is highly prevalent among older adults and may lead to increased risk of depressive symptoms. In both cross-sectional and longitudinal analysis, we quantified the association between HL and depressive symptoms, incorporating the variable nature of depressive symptoms and characterizing by race and gender. Methods: Data were from the Health, Aging, and Body Composition study. Depressive symptoms were measured using the Center for Epidemiologic Study Depression Scale short form (CES-D 10), defined as CES-D 10 score ≥10 or treatment for depression. Hearing was defined via four-frequency pure-tone average (PTA) decibel hearing level (dB HL), categorized as normal hearing (PTA ≤25 dB HL), mild HL (PTA26-40 dB HL), and ≥moderate HL (PTA > 40 dB HL). Associations at baseline were quantified using logistic regression, incident depressive symptoms using Cox proportional hazard models, and change in depressive symptoms over time using growth mixture models and multinomial logistic regression. Results: Among 2,089 older adults (1,082 women, 793 Black; mean age 74.0 SD: 2.8), moderate or greater HL was associated with greater odds of concurrent [Odds Ratio (OR):2.45, 95% CI:1.33, 4.51] and incident depressive symptoms [Hazard Ratio (HR):1.26, 95% CI:1.00, 1.58]. Three depressive symptom trajectory patterns were identified from growth mixture models: low, moderate increasing, and borderline high depressive symptom levels. Those with moderate or greater HL were more likely to be in the borderline high depressive-symptom trajectory class than the low trajectory class [Relative Risk Ratio (RRR):1.16, 95% CI:1.01, 1.32]. Conclusions: HL was associated with greater depressive symptoms. Although findings were not statistically significantly different by gender and race, estimates were generally stronger for women and Black participants. Investigation of psychosocial factors and amelioration by hearing aid use could have significant benefit for older adults' quality of life.