Post by Deborah Joye
What's the science?
In general, our cognitive abilities decline as we get older. Sometimes cognitive decline is related to a disease state, such as Alzheimer’s Disease or other dementias, but many non-disease factors likely contribute as well. To better prevent or treat age-related cognitive decline, we must first understand the many intersecting processes that contribute to it and how they interact. For example, systemic vascular issues such as rapid increases in blood pressure in mid-life can negatively impact brain health later in life. Declining vascular health also contributes to small vessel disease and white matter hyperintensities which can decrease the structural integrity of brain fibres. However, some loss of brain tissue integrity is also a normal part of aging, so consideration of normal age-related brain changes is also warranted. There may also be factors that increase the brain’s resilience to aging, such as intellectual enrichment. This week in Annals of Neurology, Vemuri and colleagues model the complex process of cognitive aging and examine several possible causal mechanisms including systemic vascular health, cognitive abilities, brain health indicators such as amyloid build-up (amyloidosis), cortical thickness, integrity of fibers in the corpus callosum, and resilience effects of education and occupation.
How did they do it?
The authors selected 1230 participants enrolled in the Mayo Clinic Study of Aging, aged 50 years or older who had undergone brain scans and had at least two clinical follow-ups. The authors also calculated a composite cardiovascular health score for each participant that considered cardiovascular and metabolic conditions such as hypertension, diabetes, and stroke prior to the brain scans. The authors analyzed brain scans of participants to quantify average cortical thickness in brain regions known to be affected by Alzheimer’s Disease pathology and created a single measure as a proxy for aging- and Alzheimer’s-related neurodegeneration. They also computed a measure of amyloid levels in each participant’s brain (high levels can indicate pre-clinical stages of Alzheimer’s disease). To quantify brain tissue integrity, the authors measured the fractional anisotropy of a region of the corpus callosum. Fractional anisotropy quantifies the directionality of a diffusion process on a scale from 0 to 1, where a value of 0 means particles can diffuse in equally in all directions such as in a liquid (or cerebrospinal fluid), whereas a value of 1 means that particles can diffuse in only one direction, usually indicating the presence of dense fibre bundles. Finally, the authors estimated a cognitive score for each participant based on their performance on tests of executive function, language, memory, and visuospatial performance.
What did they find?
The authors found that cognition generally worsened with age, and that reduced brain tissue integrity predicted later decreases in cortical thickness. The authors also found that older age was associated with lower education (younger generations tend to be more educated), worse cardiovascular and metabolic condition, and reduced brain tissue integrity. Older women had the most risk of amyloid deposition, though older men had the most risk for cortical thinning. The authors also found that the strongest predictors of lower cognitive performance were old age, male sex, high amyloid, and decreased brain tissue integrity and cortical thickness. Factors that increased resilience of the brain included higher levels of education and occupation. Interestingly, higher education was associated with better systemic vascular health, which contributed to better brain tissue integrity, increased cortical thickness, and ultimately better cognition and reduced risk of dementia, suggesting that early-life exposures had an impact on life-long health. Finally, the authors found that increased amyloid levels predicted accelerated cognitive decline and increased risk of dementia. Notably, the authors describe that cerebrovascular, amyloid/Alzheimer’s, and resilience factors have converging effects on cortical thickness and cognitive decline. Amyloid/Alzheimer’s factors generally result in neuronal loss and a decrease in grey matter integrity, but cerebrovascular and resilience factors affect white matter integrity which can subsequently impact grey matter changes.
What's the impact?
This is the first study to demonstrate that resilience and vascular factors contribute to the degradation of white matter, which then contributes to shrinkage of grey matter regions as seen in Alzheimer’s and aging. This suggests an important effect of vascular health on cognitive decline in the aging brain. This study expands our knowledge of the complex and dynamic processes of age-related cognitive decline and has broad implications for improving therapies and preventative treatments for cognitive impairment.
Vemuri et al., Amyloid, vascular, and resilience pathways associated with cognitive aging, Annals of Neurology (2019). Access the original scientific publication here.