ArticleNPJ Parkinson's disease2025
Cognitive reserve, frailty status, and risk of neurodegenerative diseases: a prospective cohort study.
Article in NPJ Parkinson's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Beyond Amyloid: Systemic and Brain Frailty as Determinants of Response to Anti-Amyloid Therapy in Alzheimer's Disease-A Conceptual Review.Medicina (Kaunas, Lithuania) · 2026Review
- Selective amygdala subregional atrophy in Parkinson's disease: from subjective cognitive decline to mild cognitive impairment.Frontiers in aging neuroscience · 2026Article
- The Versatile Roles of Exosomes in Neurodegenerative Disorders: From Pathological Mechanism and Diagnostic Biomarkers to Therapeutic Application.Drug design, development and therapy · 2026Review
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Authors and funding
7 authors.
Funding
Abstract
Cognitive frailty has emerged as an important concept in research and clinical practice, yet the combined effect of cognitive reserve and frailty on neurodegenerative disease risk remains unexplored. This study included 346,025 UK Biobank participants followed for up to 15 years. Cognitive reserve indicators were generated using latent class analysis based on educational level, occupational achievement, confiding in others, social contact, leisure activities, and television viewing time. The primary outcome was neurodegenerative disease, with secondary outcomes including Parkinson's disease, Alzheimer's disease, and all-cause dementia. During a median follow-up of 13.7 years, 5,590 new cases of neurodegenerative diseases were diagnosed. Compared to non-frail individuals, pre-frail and frail individuals had 1.47-fold (95% CI: 1.39-1.55) and 2.74-fold (95% CI: 2.46-3.06) increased risk, respectively, while high cognitive reserve conferred protection (HR = 0.82, 95% CI: 0.76-0.87). In joint effect analysis, individuals with low levels of cognitive reserve and frailty had the highest risk (HR = 3.13, 95% CI: 2.70-3.63), demonstrating significant additive interaction. Cross-sectional neuroimaging analyses showed that lower cognitive reserve levels was associated with reduced total brain volume (β = -0.161), reduced hippocampal volumes (βleft = -0.085, βright = -0.097), and increased white matter hyperintensities (β = 0.045). These findings emphasize maintaining cognitive reserve and managing frailty as modifiable factors for preventing neurodegenerative diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.