Vascular risk appears to be a strong predictor of dementia, especially in older individuals with high levels of brain beta-amyloids, and the interaction between these two risk factors might lead to a higher rate of cognitive decline, according to a recent study at the Massachusetts General Hospital.

Alzheimer’s disease (AD) is an age-related neurological disorder whose most feared outcome is dementia, along with other symptoms, such as behavioral issues, loss of motivation, and even the inability to take care of oneself. Patients suffering from AD exhibit an accumulation of plaques in their brains; these plaques, resulting from the build-up of amyloid-beta protein, have long been thought to be the cause of the disease, though other hypotheses have been put forward as well.

However, the presence of excess beta amyloids is a constant in all AD patients, and a recent study by researchers at the Massachusetts General Hospital has discovered that increased cardiovascular risk, combined with higher brain amyloid levels, is a predictor of faster cognitive decline in clinically normal elderly. [1]

A deadly interaction

Amyloid accumulation and cognitive decline aren’t equivalent: as said, AD patients affected by dementia invariably have plaques in their brains, but the converse is not true; there are people who have elevated plaque levels and never suffer from dementia. This has pushed researchers to look for other contributing factors that, together with amyloids, might trigger cognitive impairment.







Cerebrovascular disease would be a good guess, as it is one of the most common causes of dementia late in life and is often present in patients with AD. However, these two pathologies are generally considered to be separate risk factors for dementia, and MGH researchers wanted to see if the two interact to produce even higher risk; it turns out that this might just be the case.

The researchers have collected data from another study, the Harvard Aging Brain Study, which enrolled patients between 50 and 90 years of age to study the effect of brain changes on memory and cognition. Data from a cohort of 223 patients from this study was examined by MGH researchers, revealing that patients whose amyloid levels and vascular risk were both high at the beginning of the study had more rapid cognitive decline than others, and it appears that the two risk factors might interact, leading to a total risk that is higher than simply the sum of the two.

Additionally, even when other biomarkers were controlled for, vascular risk still remained a strong predictor of cognitive decline. This result is even more important because the patients enrolled for the Harvard Aging Brain Study are very healthy individuals with low levels of vascular risk; this means that however small this risk may be, it can interact with early-stage AD to speed up cognitive decline.

A two-fold benefit

The presence of high levels of beta-amyloid in the brain might be a necessary but not sufficient condition to develop cognitive decline. For this reason, it can be useful to find other markers that can help predict which individuals are at a higher risk for dementia. In the case of some of these markers, such as vascular risk factors, this is doubly advantageous. Being able to identify high-risk patients means being able to identify ideal candidates for clinical trials of AD prevention therapies while offering a way to mitigate the effects of dementia by intervening to control vascular risk.







Smoking, elevated blood pressure, and diabetes are all vascular risk factors, and they might speed up cognitive decline in elderly people with low amyloid levels—let alone in those with higher levels—therefore, appropriate medical interventions and lifestyle changes to mitigate these factors may reduce the ravages of dementia in at-risk individuals.

Literature

[1] Rabin, J.S., Schultz, A.P., Hedden, T., Viswanathan, A., Marshall, G.A., Kilpatrick, E., Klein, H., Buckley, R.F., Yang, H., Properzi, M., Rao, V., Kirn, D. R., Papp, K. V., Rentz, D.M., Johnson, K. A., Sperling, R. A, Chhatwal, J. P. (2018). Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals Findings From the Harvard Aging Brain Study. JAMA Neurology.