Cognitive performance declines 18 years before a dementia diagnosis

In a study published in the journal Neurology, researchers report that people who will go on to develop Alzheimer disease dementia over the course of the 18-year study score lower on cognitive tests than people who will not develop Alzheimer disease dementia.

Researchers measured study participants’ cognitive ability using various tests of memory, executive function, and global cognition. Tests of memory included immediate and delayed recall of a story. Executive function is a set of cognitive abilities that we use to plan and execute goal-directed behaviour. To test executive function, participants were shown number-symbol pairs, then asked to substitute a number for its corresponding geometric symbol. To test global function, researchers administered a test that is commonly used in elderly populations to measure cognitive abilities related to orientation, attention, memory, language, and visual-spatial abilities. Cognitive tests were carried out in 3-year cycles for up to 18 years.

Participants with any kind of dementia (Alzheimer or non-Alzheimer disease dementia) at the start of the study were excluded. Once the study began, Alzheimer disease dementia was diagnosed by a neurologist according to criteria specified in national guidelines, and diagnoses occurred within a year of the most recent cognitive assessment. Scientists used statistical modeling to examine associations between scores on cognitive tests and whether participants developed Alzheimer disease dementia in the ensuing 18-year study period.

THE FINDINGS

Over 2100 participants over the age of 65 took part in the study, and they were of African American and European American descent. About one in five participants developed Alzheimer disease dementia over the course of the study. The average age at diagnosis was 84 years. Diagnoses of Alzheimer disease dementia was more prevalent amoung African American participants, with about one in four participants being diagnosed, compared with European Americans where about one in six were diagnosed with Alzheimer disease dementia.

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Alzheimer disease dementia diagnoses over the course of the 18-year study 

Researchers counted how many study participants developed Alzheimer disease dementia according to the number of years before participants were diagnosed. They devised the following diagnosis intervals: less than 1 year before being diagnosed, 1 to 4 years before being diagnosed, 4 to 7 years before being diagnosed, 7 to 10 years before being diagnosed, 10 to 13 years before being diagnosed, and 13 to 18 years before being diagnosed with Alzheimer disease dementia. 

The percentage of African American individuals who were diagnosed with Alzheimer disease dementia stayed about the same across each of the diagnosis intervals and ranged from 22% to 26%. The percentage of European American individuals who were diagnosed with Alzheimer disease dementia increased from 10% (13 to 18 years before being diagnosed) to 17% (less than one year before being diagnosed).

Associations between cognitive test scores and Alzheimer disease dementia diagnosis

Researchers constructed a single overall cognitive test score that encompassed participants’ scores on all of the cognitive tests. They then calculated average overall cognitive scores for people who were not diagnosed with Alzheimer disease dementia and compared them to the average scores of the people who were diagnosed. For each of the diagnosis intervals listed above, the cognitive test scores of the people who went on to develop Alzheimer disease dementia were significantly lower than the cognitive test scores of the people who did not develop Alzheimer disease dementia. The differences between the test scores were smaller towards the longer times before being diagnosed, yet cognitive test scores for those who developed Alzheimer disease dementia were still statistically lower than those who did not.

“Cognitive impairment can occur as many as 18 years before a clinical diagnosis of Alzheimer disease dementia.”

For each of the diagnosis intervals, researchers calculated odds ratios, which estimate the association between cognitive test scores and being diagnosed with Alzheimer disease dementia. Over the course of the 18-year study, the overall cognitive test scores predicted a clinical diagnosis of Alzheimer disease dementia. Cognitive test scores more strongly predicted Alzheimer disease dementia diagnoses towards the shorter diagnosis intervals.  Towards the longer diagnosis intervals, the association between overall cognitive test score and developing Alzheimer diseases dementia was lower, but still predicted a diagnosis. For each of the diagnosis intervals, the association between overall cognitive test score and an Alzheimer disease dementia diagnosis was 1.5-fold to 2.5-fold greater for European Americans than African Americans.

 

RELEVANCE OF THE STUDY

Previous studies have shown that a decline in cognitive performance can be detected as many as 10 or 12 years before an Alzheimer disease dementia diagnosis. This study addresses a gap in the literature because it was not known that cognitive impairment could occur as many as 18 years before a clinical diagnosis of Alzheimer disease dementia. This study further advances our understanding because the early stages of Alzheimer disease dementia (before a clinical diagnosis) have not been well-studied in minority populations. This study provides evidence of the effects of impaired cognition as it relates to future Alzheimer disease dementia diagnoses in African American and European American populations. The results of this study also align with a previous study which provided evidence that a decline in performance on visual memory tests can predict Alzheimer’s disease more than ten years before receiving a clinical diagnosis.