Cognitive Decline May Begin in Middle Age



Cognitive decline may begin as early as age 45, according to a study published in the January 5 online BMJ.

Previous research has indicated that cognitive function does not decrease before age 60, although that viewpoint has not been universally accepted. “The age at which cognitive decline begins is important because behavioral or pharmacologic interventions designed to alter cognitive aging trajectories are more likely to work if they are applied when individuals first begin to experience decline,” stated Dr. Archana Singh-Manoux, Research Director at INSERM, the French National Institute of Health and Medical Research in Paris, and colleagues.

The Whitehall II Prospective Cohort Study
To investigate the onset age of cognitive decline, the research group used data from the Whitehall II prospective cohort study, which was established in 1985 on 10,308 British civil servants (73% of those invited), ages 35 to 55. The study design consists of clinical examinations every four to five years focusing on anthropometry, cardiovascular and metabolic risk factors, and disease. In the present study, data were analyzed from 7,390 (5,198 men) of the 10,308 study participants enrolled at inception. Those included in the analyses had higher education levels and were younger than those who had withdrawn from the study or died before the start of cognitive screening.

At three clinical examinations over 10 years (1997, 2002, 2007), the participants, ages 45 to 70 in 1997, completed a battery of cognitive tests, including the Alice Heim 4-I (AH4-I), which evaluates inductive reasoning by measuring the ability to identify patterns, principles, and rules. In addition, participants completed a verbal memory test, vocabulary test, and measures of phonemic and semantic fluency.

The study participants were grouped into five age categories—45 to 49, 50 to 54, 55 to 59, 60 to 64, and 65 to 70—and the investigators found that all cognitive scores, with the exception of vocabulary, declined for all age categories. Thus, decline was seen even in the 45 to 49 group, though the rate of decline was greater in older participants.

In men ages 45 to 49 at baseline, the 10-year decline rate in reasoning (change/range of test x 100) was –3.6%, while men ages 65 to 70 at baseline showed a 10-year decline rate of –9.6%. Women in the corresponding age categories had a –3.6% decline rate and –7.4% rate, respectively.

However, comparisons of longitudinal and cross-sectional effects of age indicated that cognitive decline in women may have been overestimated due to cohort differences in education, as younger women are more educated, noted Dr. Singh-Manoux. Although longitudinal analysis showed that reasoning scores in women ages 45 to 49 declined by –3.6%, the cross-sectional effects of age suggested a decline rate of –11.4%.

Implications for Future Research
The researchers concluded that cognitive decline is found in middle age, which points to the value of potential midlife interventions for dementia such as aggressively controlling behavioral and cardiovascular risk factors. “There is emerging consensus that ‘what is good for our hearts is good for our heads,’” the study authors wrote.

Most research on cognitive decline assesses risk factors and trajectories in elderly people and assumes that cognitive decline in those younger than 60 is not clinically important, they explained.

“I don’t think that clinical practice is going to change in the short term,” Dr. Singh-Manoux told Neurology Reviews, “but it is likely that clinicians will take [into account] the fact that adverse cognitive outcomes in old age are the result of long-term processes.”

She added, “In the future, better understanding of cognitive aging trajectories is likely to lead to age-specific norms of cognitive performance in order to be able to detect poor cognitive function. However, this is very much in the future and considerable work is also required to establish associations between cognition in midlife and dementia in old age.”

The investigators noted that the study’s results have profound implications for designing research used in studies of aging. “Future research needs to identify the determinants of cognitive decline and assess the extent to which the cognitive trajectories of individuals are modifiable.… Determining the age window at which potential interventions are likely to be most beneficial is also a crucial next step,” the study authors stated.

—Lauren LeBano

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