Association of Cognitive Function Trajectories in Centenarians With Postmortem Neuropathology, Physical Health, and Other Risk Factors for Cognitive Decline

Abstract

IMPORTANCE Understanding mechanisms associated with prolonged cognitive health in combination with exceptional longevity might lead to approaches to enable successful aging. OBJECTIVE To investigate trajectories of cognitive functioning in centenarians across domains, and to examine the association of these trajectories with factors underlying cognitive reserve, physical health, and postmortem levels of Alzheimer disease (AD)-associated neuropathology. DESIGN, SETTING, AND PARTICIPANTS This cohort study used neuropsychological test data and postmortem neuropathological reports from Dutch centenarians who were drawn from the 100-plus Study between January 2013 and April 2019. Eligible participants self-reported being cognitively healthy, which was confirmed by a proxy. Data analysis was performed between June 2019 and June 2020. EXPOSURES Age, sex, APOE ε genotype, factors of cognitive reserve, physical health, and AD-associated neuropathology (ie, amyloid-β, neurofibrillary tangles, and neuritic plaques). MAIN OUTCOMES AND MEASURESIn annual visits (until death or until participation was no longer possible), centenarians underwent an extensive neuropsychological test battery, from which an mean z score of global cognition, memory, executive functions, verbal fluency, visuospatial functions, and attention/processing speed was calculated. Linear mixed models with a random intercept and time as independent variable were used to investigate cognitive trajectories, adjusted for sex, age, education, and vision and hearing capacities. In a second step, linear mixed models were used to associate cognitive trajectories with factors underlying cognitive reserve, physical health at baseline, and AD-associated neuropathology. RESULTSOf the 1023 centenarians approached, 340 were included in the study. We analyzed 330 centenarians for whom cognitive tests were available at baseline (239 [72.4%] women; median [interquartile range] age of 100.5 [100.2-101.7] years), with a mean (SD) follow-up duration of 1.6 (0.8) years. We observed no decline across investigated cognitive domains, with the exception of a slight decline in memory function (β, −0.10 SD per year; 95% CI, −0.14 to −0.05 SD; P < .001).

Association of Social Support With Brain Volume and Cognition

“…Studies 1 , 2 indicate that not all older adults with substantial neuropathology attributable to Alzheimer disease and related disorders (ADRD) develop dementia. Cognitive resilience is a theoretical concept that attempts to explain this general capacity to remain cognitively unimpaired despite age- or ADRD-related pathological changes, 3 , 4 , 5 , 6 so clarifying these pathways has important implications for dementia prevention initiatives.…”

Are Brain and Cognitive Reserve Shaped by Early Life Circumstances?

“…Although neuropathological signs of dementia disorders can often be demonstrated in brains of patients, the degree to which clinical symptoms are present does mostly not show a one-to-one relation with the amount of neuropathology present. An illustrative example of this has been provided by the 100-plus Study, which is a prospective cohort study of centenarians in the Netherlands who were cognitively healthy during inclusion into the study ( Beker et al, 2021 ). Postmortem observations in cohort members revealed that the centenarians were not without neuropathology, but showed varying loads of amyloid-β, neurofibrillary tangles, and neuritic plaques, which were however not associated with cognitive performance or decline ( Beker et al, 2021 ).…”

The Role of the Primary Care Physician in the Management of Parkinson’s Disease Dementia

“…In addition to above mentioned risk factors [7], genetic risk factors are concerning too. One gene, identified to be a risk factor, is the apolipoprotein E gene which presents in three allelic forms (ε2, ε3, and ε4), of which the ε4 allele is a risk factor for AD [23,24]. Recognizing some other factors in PD patients is also important for early diagnosis of PDD [25,26].…”