The wiser mind mourns less for what age takes away than what it leaves behind.William Wordsworth, The Fountain
The wiser mind mourns less for what age takes away than what it leaves behind.
William Wordsworth, The Fountain
As a greater proportion of the world’s population live beyond age 65 years, there is increasing awareness of age-related differences in cognitive ability and a rising interest in finding ways to maintain healthy brain aging with the hope to avoid dementia. Although conventional wisdom stresses the inevitable decline of cognitive ability with age, seminal work by Wilson et al1 finds that individual trajectories of cognitive ability vary greatly, suggesting that at least some of the age-related differences in cognitive ability are due to incipient disease. Conventional wisdom also stresses that incipient or clinically expressed Alzheimer disease (AD) explains most cognitive decline and incident dementia among older individuals. The negative impact of incipient AD on cognitive ability among apparently cognitively normal older individuals is further supported by the long prodromal period of the AD process. The advent of in vivo amyloid imaging (and even eventually tau imaging) has stimulated intense interest regarding the role of incipient AD in relationship to cognitive aging. Early reports suggest a strong relationship between memory performance and cortical amyloid retention in a group of individuals with various degrees of cognitive ability. Later studies also found that increased cerebral amyloid burden, which is highly associated with age and the apolipoprotein E ε4 (APOE ε4) genotype2 among cognitively normal individuals, is associated with subtle declines in cognitive performance3 and increased risk for future dementia.4 This work and the increasing availability of biological markers of AD pathology have led to a proposed biological cascade model of AD5 and reevaluation of diagnostic criteria for AD.6 If one ascribes religiously to the concept that a large proportion of cognitive differences with age are driven by incipient disease, then one might expect that memory performance—a cognitive ability that changes most dramatically with age and is common to AD—would follow increasing levels of associated cerebral amyloid and be strongly associated with hippocampal atrophy. In their article, Jack et al7 present new information that challenges the notion that amyloid accumulation explains memory performance across the entire age range. Importantly, this work does not only address the likely highly significant impact of cerebral amyloid accumulation on dementia risk, but also extends current knowledge relating to the impact of the aging process across the spectrum of ages 30 to 95 years to brain structure, amyloid accumulation, and memory performance among cognitively normal individuals.
DeCarli C. A Call for New Thoughts About What Might Influence Human Brain Aging: Aging, Apolipoprotein E, and Amyloid. JAMA Neurol. 2015;72(5):500–502. doi:10.1001/jamaneurol.2015.33
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