Cognitive Clock Predicts Brain Health

Cognitive age — assessed by a novel tool known as a “cognitive clock” — predicted adverse health outcomes better than chronological age, two independent datasets showed.

A measure of cognitive performance, cognitive age was a strong prognostic indicator of dementia, mild cognitive impairment, and mortality, and was associated more strongly with neuropathology and brain atrophy than chronological age, reported Patricia Boyle, PhD, of Rush University Medical Center in Chicago, and colleagues in Alzheimer’s & Dementia.

“Alzheimer’s and other diseases of the brain accumulate slowly over time as people get older,” Boyle said in a statement. “Age is widely recognized as the main risk factor for Alzheimer’s disease, but it’s a very imperfect predictor, since not everyone develops dementia as they age.”

The cognitive clock provides a specific estimate of cognitive age and can help detect who’s at highest risk of developing cognitive impairment in the coming years, Boyle noted.

“For some people, cognition remains fairly stable as they age,” she said. “But, for others, cognition declines slowly over time, and still others show steep declines.”

To construct the cognitive clock, Boyle and colleagues used long-term cognitive testing data from three studies: the Rush Memory and Aging Project of people who had lived in greater Chicago, the Religious Orders Study of older Catholic clergy from across the U.S., and the Chicago Health and Aging Project, a biracial population-based study.

A total of 1,057 deceased participants in the Memory and Aging Project and the Religious Orders Study with no cognitive impairment at baseline had yearly cognitive assessments including the Mini-Mental State Exam (MMSE) for up to 24 years. Participants also had medical history assessments, neurologic examinations, neurocognitive tests, and brain autopsy.

At baseline, participants were age 79 on average and had a mean 16 years of education, as well as a MMSE of 28.4. Most participants (69%) were female. Participants died at a mean age of 89 with mean MMSE proximate to death of 23.5. At death, 443 people had no cognitive impairment, 232 had mild cognitive impairment, and 316 had Alzheimer’s dementia.

The researchers modeled patterns of cognitive decline to produce estimates of cognitive age. After aligning cognitive trajectories to the cognitive clock, they determined an individual’s position on the clock at a given time point — their cognitive age — to make inferences about brain health. They found clear distinctions among people who had no cognitive impairment, mild cognitive impairment, and Alzheimer’s dementia when they modeled trajectories using cognitive age, but no such distinctions when they used chronological age.

Compared with chronological age at death, an older cognitive age was associated with lower cognition, higher frequency of and more rapid time to dementia diagnosis, more rapid time to death, and greater burden of neuropathology. An independent validation sample of 2,592 participants from the Chicago Health and Aging Project confirmed the predictive utility of cognitive age.

The cognitive clock may aid aging research and offer a new tool to identify at-risk individuals, Boyle noted.

“It is very difficult to develop a test or biomarker that accurately predicts health outcomes on an individual level,” she said. “This has been a longstanding challenge in aging research. However, we are hoping that with additional research and validation, we may be able to extend the approach applied here to clinical settings.”