BACKGROUND
Adults with Down syndrome (DS) have a high risk for Alzheimer's disease (AD). While exercise improves cognition and brain health in the general population, few long-term studies have evaluated its effects in DS.
OBJECTIVE
We examined the impact of a 12-month remotely delivered exercise program on cognitive function and brain volume in adults with DS.
METHODS
81 adults with DS (mean age = 27 years) were randomized to high-frequency remote exercise (3 sessions/week, RH), low-frequency remote exercise (1 session/week, RL), or a support and education control (SE). Cognitive function was assessed using the DS-adapted Cambridge Neuropsychological Test Automated Battery (CANTAB), and brain volumes were measured via MRI at baseline and 12 months.
RESULTS
There were no significant changes in any group in executive function or episodic memory (all p > 0.05), but the RH arm significantly improved processing speed across the 12-month intervention (EMM change: 0.17; p = 0.04). No between-group differences were observed for changes in overall cognitive scores. The RL group showed a decrease in total grey matter volume (EMM change -0.82; p = 0.02) and the RH group had no change (EMM change: 0.08; p = 0.72), yielding a significant group effect across time (EMM: 0.90; p = 0.04). Additionally, the RH arm had an increase in right hippocampal volume over 12 months (EMM change: 0.004; p = 0.04).
CONCLUSION
The improvements in reaction time, right hippocampal volume, and grey matter preservation suggest that structured exercise may influence cognition and brain health in adults with DS.
CLINICAL TRIALS REGISTRATION
NCT04048759.
L. Ptomey, A. Aschenbrenner, B. Helsel et al.· Disability and Health Journa...· 0 citations
Background About one third of amyloid positive, cognitively normal individuals develop mild cognitive impairment or clinical Alzheimer dementia (AD) over 5 years of follow-up. Sensitive cognitive measures, in addition to biomarkers of amyloid pathology, add to the efficiency of secondary prevention trials by identifying cognitively normal individuals at greatest risk of clinical progression. The Stages of Objective Memory Impairment (SOMI) system, based on the picture version of the Free and Cued Selective Reminding Test with immediate recall (pFCSRT+IR), predicted clinical progression in two observational studies. Objective Our objective was to extend SOMI’s findings to clinical trials using participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s(A4) study. Methods Eligible participants were cognitively normal, had a Clinical Dementia Rating (CDR) =0, an elevated amyloid level, the pFCSRT+IR, pTau217, and longitudinal data on the CDR. Cox proportional hazards model was used to assess the association of baseline SOMI stage for clinical progression defined by time to the first of 2 consecutive CDRs > 0 or CDR>0 at last assessment. The sample was censored at 4.5 years of follow-up. Results Of the 911 eligible participants, mean age was 72 years, 59% were female, 62% were APOE ε4 carriers, and 37% progressed over 4.5 years. Hazard ratios (HR) for progression were estimated with follow-up time as the timescale and the SOMI 0 group as the reference. The HRs for progression across SOMI stage increased from 1.48(1.15–1.92 p=.003) for SOMI-1, to 1.83 (1.32–2.54, p ≤ 0.001) for SOMI-2, and to 3.04 (1.97–4.68, p ≤ 0.001) for SOMI 3/4. SOMI remained an independent and significant predictor when pTau217 was added to the model. Conclusion SOMI’s risk profile in A4 was similar to prior findings in observational cohorts. SOMI provides a low-cost, non-invasive enrichment tool for identifying individuals at risk for early cognitive decline in secondary prevention trials.
Priyanka Kumari, R. Lipton, A. Aschenbrenner et al.· The journal of prevention of...· 0 citations
ABSTRACT INTRODUCTION Early detection of cognitive decline in Alzheimer's disease (AD), particularly in preclinical stages, is critical for evaluating therapeutic interventions. Traditional cognitive assessments often require lengthy in‐person visits, and may therefore limit scalability for younger, trial‐ready populations for primary and secondary prevention studies. We evaluated the feasibility, reliability, and validity of high‐frequency remote digital cognitive assessments in individuals with autosomal dominant AD (ADAD). METHODS One hundred twenty‐three mutation carriers and non‐carriers from the Dominantly Inherited Alzheimer Network Trials Unit from 20 international sites (Ages 19–66 years) completed remote assessments via personal smartphones, prompted four times daily for 7 days (≈ 3 minutes per session), and conventional in‐clinic cognitive testing at baseline. Adherence, between‐person reliability, test–retest reliability (intraclass correlation coefficients [ICCs]), construct validity (confirmatory factor analysis), and sensitivity to clinical disease progression were evaluated. RESULTS Remote measures demonstrated excellent reliability (ICCs > 0.90 after just 10 sessions) and strong construct validity, with tasks loading onto memory, attention, and executive function domains. A composite of the remote tests slightly outperformed a traditional composite at separating mutation carriers from non‐carriers. Average adherence to the study protocol was 42%, lower that observed in previous studies of older adults. DISCUSSION High‐frequency remote cognitive assessment is feasible, reliable, and valid in a relatively young international ADAD cohort. This approach offers substantial utility for clinical trials, including improved accessibility and enhanced reliability, supporting its integration into early‐intervention studies.
A. Aschenbrenner, H. Wilks, Matthew S. Welhaf et al.· Alzheimer's & Dementia· 1 citation
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