Alzheimer's Imaging Consortium

Background: Though frailty is common in aging, its impact on varied health outcomes has been grossly understudied among rural Indians. We aimed to cross-sectionally examine the impact of physical frailty on 13 health outcomes and brain structure in this population.

Method: Participants (n=5302) were non-demented, aging individuals (=45 years) from the ongoing Srinivaspura Aging Neuro Senescence and Cognition (SANSCOG) cohort in rural southern India. Physical frailty was evaluated using a modified version of Fried's criteria, and participants were classified as non-frail, pre-frail and frail. Cognitive functioning was assessed using a comprehensive, culture- and education-fair battery (COGNITO) spanning multiple cognitive domains. Psychological assessments included Generalized Depression Scale (GDS-30), Generalized Anxiety Disorder (GAD-7) scale and Pittsburgh Sleep Quality Index (PSQI). Cohen's Social Networking Index (SNI) and Instrumental Activities of Daily Living for Elderly (IADL-E) were used to assess social networking and functional outcomes, respectively. Multimorbidity was assessed using self-reported/objective measures. A subset of participants (n=981) underwent 3-Tesla brain MRI. Regional brain volumes (total grey matter, total white matter, right/left hippocampus, parahippocampus, entorhinal cortex, cuneus and precuneus) and WMH volume were derived using standard protocols. Multivariable Linear/logistic regression models were used, adjusting for age, sex, education, income, waist-to-hip ratio, tobacco and alcohol use.

Result: Frailty was significantly associated with poorer cognitive performance, overall (ß=-0.14 [-0.23,-0.05] and for attention (ß=-0.15 [-0.28,-0.02]), language (ß=-0.24 [-0.41,-0.08], visuospatial (ß=-0.13 [-0.30,0.03]) and executive functioning (ß=-0.20 [-0.35,-0.04]), higher depression (ß=-5.41 [4.77,6.05]) and anxiety (ß=-2.34 [1.76,2.92]) scores, poorer sleep quality (ß=0.05 [-0.50,0.59]), lower SNI scores (ß=-0.58 [-0.68,-0.48]), higher cognitive (ß=3.41 [2.61,4.21]) and physical disability (ß=3.34 [2.53,4.14]) scores and higher odds of multimorbidity (AOR=1.41 [1.10,1.82]). Prefrailty was associated with poorer overall cognition (ß=-0.04 [-0.07,-0.005]) and visuospatial ability (ß=-0.07 [-0.13,-0.003], higher depression (ß=1.91 [1.62,2.21]) and anxiety (ß=0.71 [0.48,0.93]) scores, lower SNI scores (ß=-0.14 [-0.19,-0.10]), higher cognitive (ß=0.80 [0.43,1.17]) and physical disability (ß=0.71 [0.34,1.08]) scores. Frailty and prefrailty were not significantly associated with any of the brain MRI parameters.

Conclusion: Physical frailty is associated with multiple adverse health outcomes but not with brain structural parameters, cross-sectionally. Early identification and mitigation of frailty could potentially reduce dementia risk and improve overall health and functioning in the aging population.