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Cardiovascular health and brain aging : a population-based MRI study

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posted on 2024-09-03, 06:09 authored by Yuanjing LiYuanjing Li

Deterioration of brain structure and cognitive function occurs as individuals reach advanced age. The former can be observed through various markers of cerebral small vessel disease on magnetic resonance imaging (MRI) scans and the later can be assessed by neuropsychological tests and clinical examinations. In addition, maintaining a favorable cardiovascular health (CVH) status may contribute to delaying brain aging. Having a higher cognitive reserve (CR) capacity may contribute to preserving cognitive function even in the presence of brain damage. In this thesis, we aimed to examine the progression and interrelationships of MRI markers of structural brain aging and the association between the progression of these markers and cognitive decline. Furthermore, we aimed to investigate whether maintaining a favorable CVH status would be related to a slower deterioration of brain structure and whether having a higher CR capacity would be associated with a lower risk of cognitive deterioration and death. Data were derived from the population-based Swedish National study on Aging and Care in Kungsholmen from 2001–2004 to 2016–2019 and the MRI sub-study from 2001–2003 to 2007–2010.

Study I: This six-year follow-up study showed that the progression rate of cerebral small vessel disease markers including expansion rates of white matter hyperintensities (WMHs) and lateral ventricles, incidence of lacunes, and shrinkage rate of gray matter volume, but not the progression rate of perivascular spaces (PVSs), steadily increased with aging (P < 0.05). The progression rate of regional WMHs was faster in males than in females and in people without a university degree than those with a degree (P < 0.05). In addition, a higher load of microvascular lesions (i.e., WMHs, PVSs, and lacunes) at baseline was related to faster progression of both microvascular lesions (WMHs and lacunes) and gray matter atrophy (P < 0.05).

Study II: This follow-up study showed that a greater burden of WMHs at baseline was associated with a faster decline in executive function, letter fluency, perceptual speed, and global cognition over 15 years (P < 0.05), but not in episodic or semantic memory. The faster deterioration in category fluency was linked to greater periventricular WMHs at baseline only in people carrying the APOE-ε4 allele (multivariable-adjusted β-coefficients and 95% confidence interval [CI]: -0.018, -0.031– -0.004). Accelerated decline in perceptual speed over 15 years was linked to a faster increase in deep and periventricular WMHs during the first six years, and accelerated decline in executive function and global cognition was linked to a faster increase in deep WMHs during the first six years (P < 0.05).

Study III: This six-year follow-up study showed that compared to the unfavorable global CVH profile, the intermediate-to-favorable profiles were associated with a slower accumulation of WMHs (multivariable-adjusted β-coefficients and 95% CI: -0.019, -0.035– -0.002 and -0.018, -0.034– -0.001, respectively). Intermediate-to-favorable biological CVH profiles were associated with a slower WMH increase among people aged 60–72 years, but not in those aged 78 years and above. Furthermore, a higher metabolic genetic risk was linked to a faster accumulation of WMHs in people with intermediate-to-favorable global or behavioral CVH profiles, but not in those with favorable CVH profiles (P for both interactions = 0.001).

Study IV: This 15-year follow-up study revealed that a higher composite CR score, which was estimated from early-life education, midlife work complexity, late-life leisure activities, and late-life social network, was associated with a reduced risk of transition from normal cognition to cognitive impairment, no dementia (CIND) (multivariable-adjusted hazards ratio and 95% CI: 0.78, 0.72–0.85) and death (0.85, 0.79–0.93) and from CIND to death (0.82, 0.73–0.91), but not from CIND to dementia neither from CIND to normal cognition (P > 0.05). The risk of transitions from normal cognition to CIND or death did not change after controlling for brain aging markers, while the risk of transition from CIND to death became not significant. Furthermore, a higher CR score was associated with a lower risk of transition from CIND to death among people aged 60–72 years (0.65, 0.54–0.77) while not among those aged 78 years and above (0.87, 0.75–1.01) (P for interaction = 0.010).

Conclusions: First, the deterioration of brain structure accelerates with advancing age. Cerebral microvascular lesions are associated with accelerated brain atrophy. Second, WMHs are linked to an accelerated decline in multiple cognitive domains except memory. A faster accumulation of WMHs in deep brain regions is associated with an accelerated decline in perceptual speed and executive function. Third, having a favorable CVH profile is associated with a slower progression of structural brain aging attributable to metabolic genetic risk. Finally, having a greater CR capacity might play a crucial role in preserving cognitive health and reducing mortality rate in the prodromal phase of dementia, independent of brain aging markers. The association between higher CR capacity and lower likelihood of transition from CIND to death exists particularly among people in the early stage of older adulthood.

List of scientific papers

I. Li Y, Kalpouzos G, Laukka EJ, Dekhtyar S, Bäckman L, Fratiglioni L, Qiu C. Progression of neuroimaging markers of cerebral small vessel disease in older adults: a 6-year follow-up study. Neurobiol Aging. 2022 Apr;112:204-211.
https://doi.org/10.1016/j.neurobiolaging.2022.01.006

II. Li Y, Kalpouzos G, Bäckman L, Qiu C, Laukka EJ. Association of white matter hyperintensity accumulation with domain-specific cognitive decline: a population-based cohort study. [Submitted]

III. Li Y, Laukka EJ, Dekhtyar S, Papenberg G, Speh A, Fratiglioni L, Kalpouzos G, Qiu C. Association between behavioral, biological, and genetic markers of cardiovascular health and MRI markers of brain aging: a cohort study. Neurology. 2023 Jan;100(1):e38-e48.
https://doi.org/10.1212/WNL.0000000000201346

IV. Li Y, Dekhtyar S, Grande G, Kalpouzos G, Laukka EJ, Qiu C. Association of cognitive reserve with transitions across cognitive states and death in older adults: a 15-year follow-up study. [Manuscript]

History

Defence date

2023-09-06

Department

  • Department of Neurobiology, Care Sciences and Society

Publisher/Institution

Karolinska Institutet

Main supervisor

Qiu, Chengxuan

Co-supervisors

Laukka, Erika; Dekhtyar, Serhiy; Kalpouzos, Grégoria

Publication year

2023

Thesis type

  • Doctoral thesis

ISBN

978-91-8016-959-2

Number of supporting papers

4

Language

  • eng

Original publication date

2023-08-14

Author name in thesis

Li, Yuanjing

Original department name

Department of Neurobiology, Care Sciences and Society

Place of publication

Stockholm

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