Aging, amyloid and Alzheimer’s Disease

Cognition remains an important measure of brain health and function in everyday life, however we still do not know what a cognitively healthy older adult is and how cognitive changes during the aging process are related to those observed in Alzheimer’s Disease (AD).   

Denise C Park, PhD (The University of Texas at Dallas, USA) discussed cognitive aging and the development of AD in her plenary lecture.

Integrated models of aging and AD are useful in studying the relationship between brain structure, function and cognition

As we age, decreases are seen in many cognitive measures but our experience and knowledge increases, often masking deficits in other areas such as executive functioning.¹ In an effort to understand the relationship between brain structure, function and cognition, the Scaffolding Theory of Aging and Cognition (STAC) considers the overall level of brain degradation and how brain activity compensates as we age.² The National Institute on Aging and Alzheimer's Association Research Framework has developed  a new model that integrates non-AD and AD pathology, using biomarkers of amyloid-beta (Aβ) deposition, pathogenic tau, and neurodegeneration to define AD, and determine level of cognitive function and predict change.³

Prevalence of Aβ positivity increases with age

The Dallas Lifespan Brain Study aimed to capture longitudinal changes in the brain and cognition in healthy adults from 20–89 years of age. Very different Aβ levels were seen in the brains of cognitively normal older adults. The prevalence of Aβ positivity increases with age in cognitively normal older adults,⁴ with marked increases seen in a subset of individuals ≥60 years of age,⁵ although the rate of accumulation does plateau towards disease state.⁶ These findings suggest that it takes about 10 years to transition from Aβ levels seen in normal cognition to the threshold of abnormality, and a further 20 years to reach the levels seen in mild AD.⁶ Interestingly, ApoE4 has been shown to accelerate Aβ deposition in healthy individuals.⁷

Greater Aβ burden in cognitively normal older adults is associated with memory decline

New data are suggesting that the rate of cognitive change increases as we age. In healthy adults, higher Aβ burden at baseline is associated with an increased rate of cognitive decline over 4 years, particularly in episodic memory.⁸ In fact, increased Aβ is associated with a decline in memory even in individuals with subthreshold Aβ levels.⁹

Aβ burden also seems to predict subjective memory complaints; this relationship is mediated by actual memory function but is not impacted by depression or patient anxiety. In addition, individuals with greater hippocampal activity and Aβ burden have increased memory complaints.

Future studies of adults who have maintained brain health, many of whom are Aβ free, will provide valuable information on cognitive resilience and reserve in aging.