Trajectories of Centenarian Cognitive Health are Associated with Risk Factors for Cognitive Decline

by | Feb 8, 2021 | 2021, Aging, Brain Health, Cognitive Health

Written by Joyce Smith, BS. Cognitively healthy centenarians maintained high levels of cognitive performance even when exposed to risk factors of cognitive decline, including Alzheimer’s disease and associated neuropathologies.

agingStudies have shown that during the aging process, people who are 20-90 years of age maintain their language, abstract reasoning, and visuospatial functions while their processing speed, executive functions, and episodic and working memory 1,2 tend to decline. But how resilient are cognitively healthy centenarians against further cognitive decline? Dementia risk increases exponentially with age and reaches approximately 40% per year for people aged 100 years 3,4. For those who live beyond the 100 years, researchers believe the incidence of dementia should be measurable as it continues to increase.

To make a cognitive trajectory, researchers used a perspective cohort study 5 to analyze neuropsychological test data and postmortem neuropathology reports on 320 Dutch centenarians who were participants in the 100-plus Study between January 2013 and April 2019. The study objective was to explore a possible association between the cognitive performance of cognitively healthy centenarians and their risk of cognitive decline including Alzheimer’s disease 6. Mini-Mental State Examination (MMSE) scores were used to determine baseline cognitive performance 7. To investigate the projected outcome of cognitive performance over time, researchers calculated mean z scores for global cognition, memory, executive functions, verbal fluency, visuospatial functions, and attention/processing speed based on neuropsychological test scores.

Final analysis revealed that of the 320 centenarians (median age 100.5, 72% women), at least half (56.7%) of them lived independently. The median score of the participant Mini-Mental State Examination scores was 25.2, suggesting that all participants had normal cognition at baseline. Of the participants, 79% walked independently, 66% had good vision, 56% good hearing, and 30% had a prior stroke or transient ischemic attack and 63% had hypertension. A mean follow-up of 1.6 years saw no decline in most cognitive domains with the exception of a decrease in memory function (β −0.10 SD per year (P<0.001),

A subgroup of 43 centenarians, who survived the longest and maintained a high level of cognitive health (MMSE ≥ 26 for at least 2 years after study inclusion) had slightly less memory decline (P=0.01) and attention/processing speed in 3rd year (P=0.006) compared to all centenarians. Also, compared to all centenarians, those who lived independently had better scores in all domains except executive function possibly due to their better vision and hearing, higher education and more cognitive stimulation. Postmortem findings in 44 participants showed varying loads of amyloid beta, neurofibrillary tangles, and neuritic plaques, none of which were linked to cognitive performance or decline; however, high performing centenarians had the highest stages of amyloid beta pathology but not of neurofibrillary tangles and neuritic plaques, suggesting a resilience and resistance against them. Carrying an APOE4 or APOE2 allele did not affect cognition or rate of cognitive decline suggesting the effects of APOE alleles are exerted before the age of 100 years. Based on these collective findings, researchers suggest that mechanisms underlying resilience against risk factors of cognitive decline may be responsible for the centenarians’ prolonged maintenance of cognitive function.

The study had limitations in that the sample population does not represent all centenarians, and unmeasured confounders may have influenced results.

Source: Beker, Nina, Andrea Ganz, Marc Hulsman, Thomas Klausch, Ben A. Schmand, Philip Scheltens, Sietske AM Sikkes, and Henne Holstege. “Association of Cognitive Function Trajectories in Centenarians With Postmortem Neuropathology, Physical Health, and Other Risk Factors for Cognitive Decline.” JAMA Network Open 4, no. 1 (2021): e2031654-e2031654.

© JAMA Network Open. 2021;4(1):e2031654. doi:10.1001/jamanetworkopen.2020.31654

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Posted February 8, 2021.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

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