Brain Health: how early is early enough?

How soon is early enough? The study below supports the need for lifestyle behaviours to improve Brain Health having to start early even before you are middle-aged. In this study of 40- to 54-year-old employees of the Banco Santander in Madrid, Spain who didn’t have any apparent cardiovascular disease were assessed using the 30-year Framingham cardiovascular risk score (FCRS) and other investigations to detect atherosclerosis. A proportion of the 946 of the subjects who had early atherosclerosis underwent metabolic PET imaging of their brain to assess brain metabolism.

Higher 30-year FCRS was associated with global and regional brain hypometabolism, particularly in the parietotemporal region. The carotid artery atherosclerosis burden was associated with this brain hypometabolism, which is an early biomarker of neurodegeneration. These people have poor brain health a reduced brain reserve and are at greater risk of dementia in the future. Importantly, it was hypertension that was the main driver of the high 30-year FCRS, which means we need to prevent and treat hypertension early if we want to maximise our brain health. When I say early it seems as if interventions need to start in your 30s and maybe even earlier.

The big elephant in the room is what drives essential hypertension and is there anything we can do about it? Yes, there is a lot we can do about it. Hypertension is one of the main axes of metabolic syndrome, which also includes abdominal or visceral obesity, diabetes/prediabetes, hypercholesterolaemia/dyslipidaemia and some would argue non-alcoholic fatty liver. Underlying metabolic syndrome is driven by insulin resistance and the downstream effects of insulin resistance.

We now know how to treat insulin resistance with lifestyle interventions and/or medications. The lifestyle intervention includes exercise, a healthy diet low in processed and ultra-processed carbohydrates and biohacking, i.e. using caloric restriction, intermittent fasting or ketogenic diets to flatten your area-under-the-insulin curve. Medications that are used to treat insulin resistance are not actually used to prevent metabolic syndrome but are only prescribed once a component of the disease is diagnosed. What I am saying is sort your lifestyle out and forget about popping pills. 

The message from this study is clear; cardiovascular and brain health is a lifelong challenge. Don’t think you can leave it until you are in your 40s and 50s to tackle it. This is one of the reasons why we have launched our #ThinkBrainHealth global campaign, which is underpinned by an evidence-based international consensus report 'Time matters: a call to prioritize brain health'.

The aim is to help healthcare professionals, policymakers, researchers and the general public to act early to:

1. promote public understanding that preventing brain disease is possible and that 'what’s good for the heart is good for the brain'
2. prepare healthcare professionals to manage people with or at risk of neurodegenerative brain disease
3. prioritize research and build infrastructure to enable prevention, early detection and management of neurodegenerative brain disease.

Cortes-Canteli et al. Subclinical Atherosclerosis and Brain Metabolism in Middle-Aged Individuals: The PESA Study. J Am Coll Cardiol. 2021 Feb 23;77(7):888-898.

Background: Atherosclerosis has been linked to cognitive decline in late life; however, the impact of cardiovascular risk factors (CVRFs) and subclinical atherosclerosis on brain metabolism at earlier stages remains unexplored.

Objectives: This study sought to determine the association between brain metabolism, subclinical atherosclerosis, and CVRFs in middle-aged asymptomatic individuals.

Methods: This study included 547 asymptomatic middle-aged participants (50 ± 4 years, 82% men) from the PESA (Progression of Early Subclinical Atherosclerosis) study with evidence of subclinical atherosclerosis. Participants underwent 18F-fluorodeoxyglucose (FDG)-positron emission tomography. Global brain FDG uptake and voxel-wise analyses were used to evaluate the associations of cerebral metabolism with CVRFs and atherosclerotic plaque burden in carotids and femorals assessed by 3-dimensional vascular ultrasound.

Results: Global FDG uptake showed an inverse correlation with 30-year Framingham Risk Score (FRS) (β = -0.15, p < 0.001). This association was mainly driven by the presence of hypertension (d = 0.36, p < 0.001). Carotid plaque burden was inversely associated with global brain FDG uptake (β = -0.16, p < 0.001), even after adjusting for 30-year FRS. Voxel-wise approaches revealed that the brain areas most strongly affected by hypometabolism in association with 30-year FRS, hypertension, and carotid plaque burden were parietotemporal regions (angular, supramarginal, and inferior/middle temporal gyri) and the cingulate gyrus.

Conclusions: In asymptomatic middle-aged individuals, cardiovascular risk is associated with brain hypometabolism, with hypertension being the modifiable CVRF showing the strongest association. Subclinical carotid plaque burden is also linked to reduced brain metabolism independently of CVRFs. Cerebral areas showing hypometabolism include those known to be affected in dementia. These data reinforce the need to control CVRFs early in life in order to potentially reduce the brain's midlife vulnerability to future cognitive dysfunction.

CoI: multiple

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