Decline in Cognitive Function is Small Prior to Age 65

Researchers here process the enormous set of health data found in the UK Biobank to conclude that there is comparatively little sign of cognitive decline in cohorts younger than age 65. After that, loss of function sets in quite rapidly, however. This is good news for those of us taking good care of our health, and who have a long time yet before reaching 65. Not so great for the older contingent in the population, but we really don't need any more incentives than already exist in order to forge ahead with the development of rejuvenation therapies. Repair of the damage that causes aging, and aging of the brain in particular, is the only path forward likely to produce meaningful results in the clinic over the next ten to twenty years.

Age is a key risk factor for cognitive performance. Cognitive decline is common in older ages but recently there has been interest in understanding the age at which significant decline in cognitive abilities begins. Such knowledge has implications for the design of behavioral or pharmacological interventions since they are more likely to work if they are applied when, or even years before, individuals first begin to experience decline. Efforts to date are often based on cross-sectional studies which may be confounded by 'cohort effects'. Longitudinal studies suggest evidence of cognitive decline in middle age but that age trajectories differ by sex and cognition domain or task.

Longitudinal data that span many decades generally report minimal cognitive decline before the age of 65, but such studies are rare and also subject to limitations including small sample size, selection attrition, and retest or practice effects. Researchers examined cognitive decline among ~2,500 participants aged 25 to 95 years at recruitment in the Midlife in the United States (MIDUS) study, and all cognitive domains measured showed significant but small declines over 9 years, with differences in the timing and extent of change. The largest analysis to-date included a 10 year follow-up of ~7,400 participants aged 45-70 at recruitment of the Whitehall Study. The design of this study allowed for cross-sectional and longitudinal analysis. For the former analysis, performance on several tests were progressively lower with older age categories. In longitudinal analyses, there was some evidence of greater decline at older ages and of a linear trend in decline with increasing age for some of the tests, particularly in men.

UK Biobank is a large population cohort of adults who underwent medical, sociodemographic, mental health and cognitive assessment in 2006-2010 and are being followed up at intervals. The large age-distribution and follow-up enables cross-sectional as well as longitudinal analysis of age. In the current study of individuals aged 38 to 73 at baseline, we observed significantly lower performance on memory, attention, and processing tasks across successive age groups. Reasoning scores, based on the fluid intelligence test, were higher with successive age group until 60, then dropped to less than that of under 45 year olds. Longitudinal analysis of a subset of individuals with repeated measures of four tests showed linear declines in visual memory and processing speed tasks with age but of a much lesser degree than those observed in cross-sectional analyses. Decline rates in reasoning and prospective memory did not significantly differ with age. Taken together, our findings suggest that decline in cognitive abilities before age 65 is evident but small, and that observed cross-sectional differences in cognition from middle to older adult years may be due largely to age cohort effects.


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