The balance between cognitive reserve and brain imaging biomarkers of cerebrovascular and Alzheimer's diseases

Abstract

The cognitive reserve hypothesis explains the disparity between clinical and pathological phenotypes and why, in two individuals with the same extent of neuropathology, one may be demented while the other remains cognitively intact. We examined the balance between brain magnetic resonance imaging measures of the two most common pathologies associated with brain ageing, cerebrovascular disease and Alzheimer's disease, and parameters of cerebral reserve in well-characterized participants born in 1936, for whom childhood intelligence is known. Brain magnetic resonance imaging was carried out at 1.5T using fluid attenuation inversion recovery and T(1)-weighted volumetric sequences in 249 participants. Cerebrovascular disease was quantified by measuring brain white matter hyperintensities on fluid attenuation inversion recovery images using Scheltens' scale and Alzheimer's disease was measured from volumetric data using FreeSurfer to extract whole brain volume and hippocampal volumes in turn. The effect of these measures of brain burden on life-long cognitive ageing from the age of 11 to 68 years was compared with the effect of educational attainment and occupational grade using structural equation modelling. Complete brain burden and reserve data were available in 224 participants. We found that educational attainment, but not occupation, has a measurable and positive effect, with a standardized regression weight of +0.23, on late life cognitive ability in people without cognitive impairment aged 68 years, allowing for the influence of childhood intelligence and the two most common subclinical brain pathological burdens in the ageing brain. In addition, we demonstrate that the magnitude of the contribution of education is greater than the negative impact of either neuropathological burden alone, with standardized regression weights of -0.14 for white matter hyperintensities and -0.20 for hippocampal atrophy. This study illustrates how education counteracts the deleterious effects of cerebrovascular disease and Alzheimer's disease and highlights the importance of quantifying cognitive reserve in dementia research.

Cognitive reserve impacts on inter-individual variability in resting-state cerebral metabolism in normal aging

“…Recently, there has been increasing interest in the factors that could contribute to individual differences in cognitive and cerebral aging. In particular, there is evidence that cognitive decline is attenuated in elderly people with high levels of intelligence, education, literacy, and occupational attainment (Albert et al, 1995;Christensen, 2001;Manly, Schupf, Tang, & Stern, 2005;Murray et al, 2011). The idea that individuals with stimulating lifetime experience can cope better than others with age-related neural changes and thus minimize cognitive decline has been formalized in the cognitive reserve hypothesis (Steffener & Stern, 2012;Stern, 2002Stern, , 2006Stern, , 2009Tucker & Stern, 2011).…”

Early Life Risk Factors for Stroke and Cognitive Impairment

“…These mechanisms are often referred to as the theory of cognitive reserve which proposes that greater brain integrity can protect the brain from negative neurological sequela through both 'active' and 'passive' pathways [67]. While passive cognitive reserve relates to histology and brain size, active reserve refers to the ability of redundant pathways to take over following damage to the brain [67].…”

Cognitive reserve and executive function: Effect on judgment of health and safety

“…This pattern has been observed across a wide range of brain pathologies, including moderate to severe traumatic brain injury [9], cerebrovascular disease [10], hepatitis C [11], and AD [12]. Overall, a strong body of research has found support that intellectual ability, education, and occupational attainment are associated with cognitive reserve [7,[11][12][13][14][15][16][17].…”