Biological brain age and resilience in cognitively unimpaired 70-year-old individuals

 You don't want any brain age gap as a result of your stroke, so DEMAND YOUR COMPETENT? DOCTOR  have EXACT protocols to address your 5 lost years of brain cognition due to your stroke.

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'Younger' Brain Associated With Lower Risk of Post-Stroke Cognitive Disorders April 2022

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Biological brain age and resilience in cognitively unimpaired 70-year-old individuals

Anna Marseglia, Caroline Dartora, Jessica Samuelsson, Konstantinos Poulakis, Rosaleena Mohanty, Sara Shams, Olof Lindberg, Lina Rydén, Therese Rydberg Sterner, Johan Skoog … See all authors

First published: 20 December 2024

https://doi.org/10.1002/alz.14435

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Abstract

INTRODUCTION

This study investigated the associations of brain age gap (BAG)—a biological marker of brain resilience—with life exposures, neuroimaging measures, biological processes, and cognitive function.

METHODS

We derived BAG by subtracting predicted brain age from chronological age in 739 septuagenarians without dementia or neurological disorders. Robust linear regression models assessed BAG associations with life exposures, plasma inflammatory and metabolic biomarkers, magnetic resonance imaging, and cerebrospinal fluid biomarkers of neurodegeneration and vascular brain injury, and cognitive performance.

RESULTS

Greater BAG (older-looking brains) was associated with physical inactivity, diabetes, and stroke, while prediabetes was related to lower BAG, that is, younger-looking brains. Physical activity mitigated the link between obesity and BAG. Greater BAG was associated with greater small vessel disease burden, white-matter alterations, inflammation, high glucose, poorer vascular-related cognitive domains. Sex-specific associations were identified.

DISCUSSION

Vascular-related lifestyles and health shape brain appearance. Inflammation and insulin-related processes may be keys to understanding vascular cognitive disorders.

Highlights

• BAG, reflecting deviations from CA, can indicate resilience.
• Diabetes, stroke, and low physical activity link to “older” brains (greater BAG).
• Physical activity yielded to “younger” brains in septuagenarians with obesity.
• High cerebrovascular burden, inflammation, and glucose associate with “older” brains.
• Sex differences were detected in all BAG-associated factors.

1 BACKGROUND

Individuals show different brain aging trajectories influenced by a spectrum of negative and positive life exposures across their lifespan. Unhealthy lifestyle habits (e.g., diet, sedentary behaviors) coupled with cardiometabolic risk factors and disorders (CMDs; e.g., hypertension, heart disease, diabetes, obesity) heighten the risk of cognitive disorders, including dementia.¹ Research consistently demonstrated the significant contribution of CMDs to brain atrophy and vascular brain injury, including markers of small vessel disease (SVD) and early changes in white matter microstructure.^2-4 Such structural alterations can manifest as an aged brain appearance on neuroimaging. However, the processes linking structural brain alterations to clinically manifest cognitive disorders remain largely elusive. Inflammation and disruptions in glucose and lipid metabolism could be key underlying pathways. Growing literature showed that systemic inflammation is linked to CMDs,⁵ Alzheimer's disease (AD), SVD, and dementia.^6-8 Studies examining changes in glucose and/or lipids biomarkers, alone or alongside inflammation, on the other hand, yielded mixed results.^{9, 10} Conversely, positive life exposures (e.g., high educational attainment, challenging jobs, social/physical/mental engagement) can influence brain aging fostering greater resilience.¹¹ Resilience, encompassing the brain's ability to preserve cognitive function through structural preservation (brain maintenance) or adaptation to pathology (cognitive reserve),¹² has traditionally posed challenges for biological measurements. Advancements in artificial intelligence facilitated the development of brain age models using the whole structural magnetic resonance imaging (MRI), capturing the resilience's core biological dimension.¹³ The brain age gap (BAG), derived from differences between an individual's predicted brain age (PBA) and chronological age (CA), can serve as a valuable biomarker of brain health.¹⁴ BAG is particularly promising for assessing resilience mechanisms, with negative values indicating younger brains (i.e., brain maintenance) and positive values indicating older brains (Figure 1A). In the long term, identifying the modifiable risk factors and biological processes driving BAG holds promises for uncovering neuroprotective intervention targets to improve brain health. Emerging studies have linked diastolic blood pressure, alcohol intake, and smoking to greater BAGs (older brains).^{15, 16} Also, white matter hyperintensity, that is, a SVD marker, has been linked to greater BAGs.¹⁷ However, the extent to which CMDs, vascular-related biological processes (e.g., inflammation, glucose, and lipids alterations), neurodegenerative and vascular brain injury contribute to the BAG remains poorly understood. Also, to fully realize BAG's potential as a resilience biomarker, its role in cognitive function must be clarified. While studies consistently show that greater BAG is associated with poor cognition findings across key cognitive processes in aging are less consistent.^18-21

FIGURE 1

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Brain age gap as potential biological markers of brain resilience. Panel A (left) presents a conceptual framework illustrating two complimentary resilience mechanisms (brain maintenance and cognitive reserve) based on the differences between an individual's PBA and CA, knows as the BAG. These differences can serve as personalized biomarkers of brain and/or cognitive health. Hypothetically, younger-appearing brains (negative differences, PBA < CA) suggest preserved brain structure, indicative of brain maintenance. Conversely, older-appearing brains (positive differences, PBA > CA), especially in the presence of no/minimal cognitive decline, suggest coping abilities linked to cognitive reserve. Panel B (right) shows the T1-weighted and FLAIR brain MRIs from three participants in the Gothenburg H70 Birth Cohort Studies–Birth cohort 1944. The images illustrate cases where there are no differences between PBA and CA (BAG = 0 years), a negative difference indicative of a younger-appearing brain (BAG = −3.7 years), and a positive difference indicative of an older-appearing brain (BAG = +3.7 years). BAG, brain age gap; CA, chronological age; FLAIR, fluid attenuated inversion recovery; MRI, magnetic resonance imaging; PBA, predicted brain age.