Importance: An accessible marker of both biological age and dementia risk is crucial to advancing dementia prevention and treatment strategies. Although frailty is a candidate for that role, the nature of the relationship between frailty and dementia is not well understood.
Objective: To clarify the temporal relationship between frailty and incident dementia by investigating frailty trajectories in the years preceding dementia onset.
Design, Setting, And Participants: Participant data came from 4 prospective cohort studies: the English Longitudinal Study of Ageing, the Health and Retirement Study, the Rush Memory and Aging Project, and the National Alzheimer Coordinating Center. Data were collected between 1997 and 2024 and were analyzed from July 2023 to August 2024. The settings were retirement communities, national-level surveys, and a multiclinic-based cohort. Included individuals were 60 years or older and without cognitive impairment at baseline. Included individuals also had data on age, sex, education level, and ethnicity and a frailty index score calculated at baseline.
Exposure: Frailty was the main exposure, with participants' degrees of frailty quantified using retrospectively calculated frailty index scores.
Main Outcomes And Measures: Incident all-cause dementia ascertained through physician-derived diagnoses, self- and informant-report, and estimated classifications based on combinations of cognitive tests.
Results: The participant number before exclusions was 87 737. After exclusions, data from 29 849 participants (mean [SD] age, 71.6 [7.7] years; 18 369 female [62%]; 257 963 person-years of follow-up; 3154 cases of incident dementia) were analyzed. Bayesian generalized linear mixed regression models revealed accelerations in frailty trajectories 4 to 9 years before incident dementia. Overall, frailty was positively associated with dementia risk (adjusted hazard ratios [aHRs] ranged from 1.18; 95% CI, 1.13-1.24 to 1.73; 95% CI, 1.57-1.92). This association held among participants whose time between frailty measurement and incident dementia exceeded the identified acceleration period (aHRs ranged from 1.18; 95% CI, 1.12-1.23 to 1.43; 95% CI, 1.14-1.80).
Conclusions And Relevance: These findings suggest that frailty measurements may be used to identify high-risk population groups for preferential enrolment into clinical trials for dementia prevention and treatment. Frailty itself may represent a useful upstream target for behavioral and societal approaches to dementia prevention.
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http://dx.doi.org/10.1001/jamaneurol.2024.3774 | DOI Listing |
Sports Med
December 2024
Australian Catholic University, North Sydney, NSW, Australia.
J Neurol
December 2024
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Stockholm, Sweden.
Predicting amyloid status is crucial in light of upcoming disease-modifying therapies and the need to identify treatment-eligible patients with Alzheimer's disease. In our study, we aimed to predict CSF-amyloid status and eligibility for anti-amyloid treatment in a memory clinic by (I) comparing the performance of visual/automated rating scales and MRI volumetric analysis and (II) combining MRI volumetric data with neuropsychological tests and APOE4 status. Two hundred ninety patients underwent a comprehensive assessment.
View Article and Find Full Text PDFAlzheimers Res Ther
December 2024
Shiley-Marcos Alzheimer's Disease Research Center, Department of Neurosciences, University of California, San Diego, CA, USA.
Background: Alzheimer's disease neuropathologic change (ADNC) and Lewy pathology (LP) often coexist in cognitively impaired individuals. These pathologies' relative distribution and severity may modify these individuals' clinical presentation, cognitive profile, and prognosis. Therefore, we examined the contributions of LP and concomitant ADNC to disease survival and profiles of cognitive decline in preclinical and clinical stages in a large neuropathologically diagnosed group.
View Article and Find Full Text PDFDiabetes Care
December 2024
The Welch Center for Prevention, Epidemiology and Clinical Research, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Objective: To characterize the prevalence of continuous glucose monitoring (CGM)-defined glucose abnormalities in a large, community-based population of very old adults (>75 years).
Research Design And Methods: A cross-sectional analysis of 1,150 older adults with and without diabetes who attended the Atherosclerosis Risk in Communities Study (2021-2022). Diabetes was based on a self-reported diagnosis of diabetes by a health care provider, use of diabetes medication, or a hemoglobin A1c (HbA1c) ≥6.
Alzheimers Dement
December 2024
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
Introduction: This study investigated the associations of brain age gap (BAG)-a biological marker of brain resilience-with life exposures, neuroimaging measures, biological processes, and cognitive function.
Methods: We derived BAG by subtracting predicted brain age from chronological age in 739 septuagenarians without dementia or neurological disorders. Robust linear regression models assessed BAG associations with life exposures, plasma inflammatory and metabolic biomarkers, magnetic resonance imaging, and cerebrospinal fluid biomarkers of neurodegeneration and vascular brain injury, and cognitive performance.
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