Cognitive Decline Detectable Even in Middle-Aged Adults

From Medscape Education Clinical Briefs News Author: Emma Hitt, PhD CME Author: Charles P. Vega, MD CME Released: 01/11/2012; Clinical Context There is no known cure for dementia, but there is debate as to when the process of cognitive decline begins among adults. The authors of the current study describe that neurofibrillary tangles and amyloid plaques, the pathologic hallmarks of dementia, can be found in the brains of young adults. Although cognitive performance earlier in life can help to predict an individual's future risk for dementia, there are no reliable biomarkers that indicate a higher risk for dementia. Nonetheless, there is evidence that controlling traditional cardiovascular risk factors can have a salutary effect in the prevention of dementia. But when should clinicians be concerned regarding the incipient stages of cognitive decline? The current study by Singh-Manoux and colleagues addresses this issue. Study Synopsis and Perspective Cognitive decline is detectable in persons aged 45 to 49 years and may not uniformly start later, in persons aged approximately 60 years, as previously thought, new research suggests. The study, using data from the longitudinal Whitehall II cohort study, followed participants aged 45 to 70 years at baseline using 3 cognitive assessments over a period of 10 years. The investigators report that average performance in all cognitive domains except vocabulary, which is known not to be affected by age, declined over the follow-up period in all age groups, including persons aged 45 to 49 years. Archana Singh-Manoux, MD, with the Hôpital Paul Brousse, Villejuif, France, and colleagues from the University of London, in the United Kingdom, reported their findings online January 5 in the BMJ. The Subject of Debate According to the researchers, "the age at which cognitive decline becomes evident at the population level remains the subject of debate." They add that some studies suggest that there is little evidence of cognitive decline before the age of 60 years, but they note that "this point of view…is not universally accepted." They sought to determine whether cognitive decline begins before the age of 60 years using a large sample of middle-aged adults from the longitudinal Whitehall II cohort study. The prospective cohort study, beginning in 1985 to 1988, included participants who worked in civil service departments in London. All participants (5198 men and 2192 women) were aged 45 to 70 years at the beginning of cognitive testing in the period from 1997 to 1999. Participants underwent repeated measures of cognitive function over a decade of follow-up across multiple cognitive domains. They found that cognitive scores declined in all categories (memory, reasoning, and phonemic and semantic fluency) except vocabulary; the decline was faster among older people. Over the 10-year study period, there was also a -3.6% decline in mental reasoning in men aged 45 to 49 years and a -9.6% decline in those aged 65 to 70 years. The corresponding figures for women were -3.6% and -7.4%. According to the researchers, robust evidence showing cognitive decline before the age of 60 years has important ramifications because it demonstrates the importance of promoting healthy lifestyles, particularly cardiovascular health, because there is emerging evidence that "what is good for our hearts is also good for our heads." They add that targeting patients who suffer from one or more risk factors for heart disease (obesity, high blood pressure, and high cholesterol levels) could not only protect their hearts but also safeguard them from dementia in later life. "Determining the age window at which potential interventions are likely to be most beneficial is also a crucial next step," they suggest. A "Slightly Different" Research Agenda In an accompanying editorial, Francine Grodstein, MD, associate professor of medicine at Brigham and Women’s Hospital in Boston, Massachusetts, notes that the study suggests that "it may be possible to identify those at increased risk of dementia as early as in their 40s," and that "this finding potentially has profound implications for prevention of dementia and public health." By finding cognitive decline in young adults, these researchers "have set a new benchmark for future research, and eventually clinical practice," Dr. Grodstein writes. "That is, efforts to prevent dementia may need to start in adults as young as 45 years," whereas most research has focused on those aged 65 years and older. "The major challenge will be to design prospective research studies that include much younger age groups — a dramatic change from the status quo," she writes. To begin studying risk factors for cognitive decline in middle-aged persons will require large sample sizes, "probably tens of thousands of participants," and more creativity in research methods, perhaps incorporating telephone interviews or computerized cognitive assessments. "We are entering a new era of research and prevention in dementia," Dr. Grodstein concludes. "There is probably greater hope of identifying ways to intervene in the development of dementia, but the challenge will be to change the status quo and find creative approaches to a slightly different research agenda." The study was not commercially funded. The authors and editorialists report no relevant financial relationships. BMJ. 2011;343. Published online January 5, 2012. Abstract, Editorial Study Highlights Researchers focused on the Whitehall II cohort to examine the rate of cognitive decline among middle-aged adults. Study participants were British civil servants between the ages of 35 to 55 years during study enrollment in 1985. Participants underwent cognitive testing in 3 phases during 1997 to 1999, 2002 to 2004, and 2007 to 2009. Researchers used a variety of validated instruments to assess different domains of cognitive function. The main study outcome was cognitive performance as time progressed. 7390 participants provided data for the current analysis. 70% of participants were men, and 90% were white. The cohort was fairly evenly divided among different educational levels, including achievement of less than secondary school. 63% of the study cohort underwent cognitive evaluations at all 3 follow-up points. Older age at baseline was associated with lower cognitive scores in reasoning, memory, phonemic fluency, and semantic fluency. However, it did not affect vocabulary scores. There were trends toward worse performance on multiple cognitive domains with age, with a more pronounced effect among men vs women. Compared with men 45 to 49 years old at baseline, the average decline in reasoning skills was -3.6% at ages 55 to 59 years and -9.6% at ages 65 to 70 years. The corresponding average declines among women were -3.6% and -7.4%. Results from testing of all of the other cognitive domains also declined with age, with the exception of vocabulary. On examination of cross-sectional effects of the data, differences in the level of education led to an overestimation of cognitive decline with age among women, but not men. However, longitudinal analyses did not demonstrate a substantial effect of educational level in altering the main study results. Clinical Implications Neurofibrillary tangles and amyloid plaques can be found in the brains of young adults. Although cognitive performance earlier in life can help to predict an individual's risk for dementia in the future, there are no reliable biomarkers that indicate a higher risk for dementia. Nonetheless, there is evidence that controlling traditional cardiovascular risk factors can have a salutary effect in the prevention of dementia. The current study by Singh-Manoux and colleagues suggests that cognitive decline begins in middle age and affects multiple domains, with the exception of vocabulary.