“Cognitive clock” emerges as a new way to measure brain health

By Benedette Cuffari, M.Sc.Reviewed by Emily Henderson, B.Sc.Jun 2 2021

Researchers from the Rush University Medical Center developed a novel method to monitor the brain health of patients to improve the early diagnosis and treatment of certain diseases including Alzheimer’s disease and dementia. This “cognitive clock,” which is the term that has been coined for this new screening technique, involves measuring an individual’s cognitive age, rather than their chronological age, to assess the patient’s risk of poor health outcomes.

Brain Health. Image Credit: HQuality/Shutterstock.com

Physical vs. mental aging

Aging, which is used to describe the increase in an individual’s chronological age, generally increases an individual’s risk for adverse health outcomes including dementia, disability, and mortality. While the link between advancing age and disease development has been widely documented, it is important to note that aging does not affect all people uniformly.

The cognitive decline that occurs in certain neuropathologies like Alzheimer’s disease and dementia, for example, is weakly related to the patient’s chronological age. Therefore, it appears that deteriorating brain health as a result of certain pathologic factors has a more significant impact on the development of these neurological diseases as compared to chronological age alone.

How can brain health be measured?

A considerable amount of research has been conducted over the past several decades to identify the different biomarkers that are responsible for a wide range of neurodegenerative and vascular pathologies. Despite these efforts, many of these hallmarks of brain aging cannot be identified while the patient is still alive, as they often require histopathological analysis of the brain. As a result, there remains a limited ability of healthcare practitioners to accurately assess brain health to more accurately predict the patient’s cognitive and other health outcomes.

Recently, researchers at the Rush University Medical Center in Chicago, Illinois developed the “cognitive clock” as a tool to monitor the brain health of patients by assessing their cognitive performance. The criteria for the 1,057 participants of this study included the absence of cognitive impairment at baseline, as well as a valid Mini-Mental Status Examination (MMSE) score that was repeated once a year for up to 24 years before the patients died.

During these annual clinical evaluations, the patients would undergo various neurologic examinations, cognitive assessments, and medical history interviews. Repeated MMSE scores were used as the primary cognitive measure in this study.

Some of the different questions that were incorporated into these evaluations included:

• What is today’s date?
• What town, county, and state are we in?
• I am going to name 3 objects. After I have said them, I want you to repeat them back to me. Remember what they are because I will ask you to name them again in a few minutes: Apply, Table, Penny.
• Please write a sentence.
• Take this piece of paper in your right hand, fold it in half with both hands, and put it in your lab.
• Here is a drawing. Please copy the drawing on the same piece of paper.
• Please repeat the following: No ifs, ands, or buts.
• What are the 3 objects I asked you to remember a few moments ago?

In addition to cognitive function testing, the researchers also collected the brains of test subjects after they had died for a post-mortem magnetic resonance imaging (MRI) scan, as well as neuropathologic assessment of brain sections. Taken together, the results of the participants’ yearly cognitive assessments and the pathologic findings following their death were analyzed to determine the contribution of their cognitive age or chronological age to their causes of death.

Assessing the efficacy of the “cognitive clock” approach

In their study, the researchers at Rush University found that an individual’s cognitive age, rather than their chronological age, was a better indicator of Alzheimer’s disease dementia, mild cognitive impairment (MCI), and mortality. Furthermore, cognitive age was found to more strongly be associated with neurobiological indices of brain health including neuropathology and total brain mass.

One important finding of this study is the fact that chronological age is an inadequate prognostic indicator of cognitive impairment and other adverse health outcomes. In fact, individuals of older cognitive age as compared to their chronological age at death were found to experience a higher frequency of dementia diagnosis, a more rapid time to death, a greater burden of potent neuropathologies, and overall lower cognitive scores.

Another significant finding of the current study was that cognitive age is a better predictor for Alzheimer’s disease, dementia, and death, as compared to chronological age. In fact, higher cognitive age was found to be more closely related to neurobiological indices including neuropathology and overall brain mass as compared to chronological age. Taken together, these findings indicate that a consistent evaluation of the cognitive age of patients could have an important role in the clinical setting to improve the early and accurate diagnosis of certain health conditions.