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Principal Investigator  
Principal Investigator's Name: Marco Canevelli
Institution: Sapienza University
Department: Department of Human Neuroscience
Proposed Analysis: Background Frailty is defined as a condition of reduced homeostatic reserves and increased vulnerability to stressors that expose the individual to negative health outcomes. This concept has already been explored in the field of cognitive disorders. It has been shown to increase: i) the risk of incident dementia in cognitively normal older individuals; ii) the probability of conversion to dementia in subjects with mild cognitive impairment; and iii) the risk of poorer outcomes in patients with Alzheimer's disease (AD). There is also emerging evidence that frailty can influence the neuropathological and biological changes occurring with neurodegeneration and affect their phenotypic manifestations. Hypothesis The individual frailty status can modify the relationship between candidate AD biomarkers and the cognitive manifestations occurring along the AD continuum. Aim We aim at investigating if and how frailty influences the changes in the main biomarkers of AD pathology and moderates their association with cognitive changes and dementia. Methods A measure of frailty, namely a Frailty Index, can potentially be computed in ADNI by considering the clinical variables collected during the screening and baseline procedures. The resulting variable can therefore be used in models exploring the association between the main AD biomarkers (e.g., CSF Aβ and tau, FDG PET, florbetapir PET) and their cognitive expression. References Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62. Rockwood K, Howlett SE. Age-related deficit accumulation and the diseases of ageing. Mech Ageing Dev. 2019;180:107–16. Wallace LMK, Theou O, Godin J, Andrew MK, Bennett DA, Rockwood K. Investigation of frailty as a moderator of the relationship between neuropathology and dementia in Alzheimer’s disease: a cross-sectional analysis of data from the Rush Memory and Aging Project. Lancet Neurol. 2019;18(2):177–84.
Additional Investigators