Presence of Cardiometabolic Disease Correlates with Accelerated Brain Aging

It is well known that metabolic dysfunction and cardiovascular disease correlate well with an accelerated onset and progression of neurodegenerative conditions. This is particularly evident when considering these conditions in the context of obesity. Age-related diseases are the late stage consequences of a progressive accumulation of cell and tissue damage, and so a lifestyle that accelerates those underlying damage processes will produce a greater incidence of all of the common age-related diseases. Suffering from one form of age-related disease thus implies greater odds of suffering other forms of age-related disease, as they all descend from the same roots.

As demonstrated in today's open access paper, it isn't just the end result of outright dementia that correlates with the presence of other forms of age-relate disease. Suffering from metabolic or cardiovascular disease clearly correlates with the earlier stages of brain aging as well, such as cognitive decline, measures of brain volume, and the presence of small white matter hyperintensities that result from ruptured capillaries in brain tissue. Some of these harms derive from the underlying forms of damage that cause age-related disease, others are downstream of vascular aging or the inflammation of metabolic disease, others are a mix.

Cardiometabolic disease, cognitive decline, and brain structure in middle and older age

Cardiometabolic diseases (CMDs), a cluster of related conditions including type 2 diabetes (T2D), heart disease (HD), and stroke, are well-established individual risk factors for cognitive/brain aging and dementia. Cardiometabolic multimorbidity - the coexistence of ≥ 2 CMDs in the same individual - has risen greatly with population aging and is estimated to affect up to 30% of older adults. Recent studies have described a dose-dependent increase in dementia risk with one, two, and three co-morbid CMDs. However, less is known about the combined influence of CMDs on the subtle cognitive decline and brain structural changes that can occur in the decades before dementia diagnosis.

Brain magnetic resonance imaging (MRI) studies have linked cardiometabolic multimorbidity and unfavorable cardiovascular risk profiles to lower volumes of subcortical structures and poorer white matter microstructural integrity in older age. Moreover, recent studies suggest that cardiovascular and metabolic risk factors could be associated with vascular lesions already in middle age. However, evidence is lacking on the relationship between cardiometabolic multimorbidity and brain structure at different stages of life.

In the present study, using longitudinal data from adults that were middle-aged, younger than 60 years, as well as individuals older than 60 years in the UK Biobank, we aimed to (1) assess the association between cardiometabolic multimorbidity and changes in global and domain-specific cognitive function and (2) identify the brain regions that are possibly associated with cardiometabolic multimorbidity in middle and older age. 46,562 dementia-free UK Biobank participants completed a cognitive test battery at baseline and a follow-up visit 9 years later, at which point 39,306 also underwent brain magnetic resonance imaging. CMDs were ascertained from medical records.

A higher number of CMDs was associated with significantly steeper global cognitive decline in the older but not middle aged cohort. Additionally, the presence of multiple CMDs was related to smaller total brain volume, gray matter volume, white matter volume, hippocampal volume, and larger white matter hyperintensity volume, even in middle age. Thus CMDs are associated with cognitive decline in older age and worse brain structural health beginning already in middle age.

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