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Cerebral arterial pulsatility is linked to hippocampal microvascular function and episodic memory in healthy older adults.

ABSTRACT: Microvascular damage in the hippocampus is emerging as a central cause of cognitive decline and dementia in aging. This could be a consequence of age-related decreases in vascular elasticity, exposing hippocampal capillaries to excessive cardiac-related pulsatile flow that disrupts the blood-brain barrier and the neurovascular unit. Previous studies have found altered intracranial hemodynamics in cognitive impairment and dementia, as well as negative associations between pulsatility and hippocampal volume. However, evidence linking features of the cerebral arterial flow waveform to hippocampal function is lacking. We used a high-resolution 4D flow MRI approach to estimate global representations of the time-resolved flow waveform in distal cortical arteries and in proximal arteries feeding the brain in healthy older adults. Waveform-based clustering revealed a group of individuals featuring steep systolic onset and high amplitude that had poorer hippocampus-sensitive episodic memory (p = 0.003), lower whole-brain perfusion (p = 0.001), and weaker microvascular low-frequency oscillations in the hippocampus (p = 0.035) and parahippocampal gyrus (p = 0.005), potentially indicating compromised neurovascular unit integrity. Our findings suggest that aberrant hemodynamic forces contribute to cerebral microvascular and hippocampal dysfunction in aging.

SUBMITTER: Vikner T

PROVIDER: S-EPMC8217890 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Cerebral arterial pulsatility is linked to hippocampal microvascular function and episodic memory in healthy older adults.

Vikner Tomas T Eklund Anders A Karalija Nina N Malm Jan J Riklund Katrine K Lindenberger Ulman U Bäckman Lars L Nyberg Lars L Wåhlin Anders A

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20210114 7

Microvascular damage in the hippocampus is emerging as a central cause of cognitive decline and dementia in aging. This could be a consequence of age-related decreases in vascular elasticity, exposing hippocampal capillaries to excessive cardiac-related pulsatile flow that disrupts the blood-brain barrier and the neurovascular unit. Previous studies have found altered intracranial hemodynamics in cognitive impairment and dementia, as well as negative associations between pulsatility and hippocam ...[more]

PMID: 33444091

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Project description:ObjectiveAge-related hippocampal atrophy is associated with memory loss in older adults, and certain hippocampal subfields are more vulnerable to age-related atrophy than others. Cardiorespiratory fitness (CRF) may be an important protective factor for preserving hippocampal volume, but little is known about how CRF relates to the volume of specific hippocampal subfields, and whether associations between CRF and hippocampal subfield volumes are related to episodic memory performance. To address these gaps, the current study evaluates the associations among baseline CRF, hippocampal subfield volumes, and episodic memory performance in cognitively unimpaired older adults from the Investigating Gains in Neurocognition Trial of Exercise (IGNITE) (NCT02875301).MethodsParticipants (N = 601, ages 65-80, 72% female) completed assessments including a graded exercise test measuring peak oxygen comsumption (VO2peak) to assess CRF, cognitive testing, and high-resolution magnetic resonance imaging of the hippocampus processed with Automated Segmentation of Hippocampal Subfields (ASHS). Separate linear regression models examined whether CRF was associated with hippocampal subfield volumes and whether those assocations were moderated by age or sex. Mediation models examined whether hippocampal volumes statistically mediated the relationship between CRF and episodic memory performance. Covariates included age, sex, years of education, body mass index, estimated intracranial volume, and study site.ResultsHigher CRF was significantly associated with greater total left (B = 5.82, p = 0.039) and total right (B = 7.64, p = 0.006) hippocampal volume, as well as greater left CA2 (B = 0.14, p = 0.022) and dentate gyrus (DG; B = 2.34, p = 0.031) volume, and greater right CA1 (B = 3.99, p = 0.011), CA2 (B = 0.15, p = 0.002), and subiculum (B = 1.56, p = 0.004) volume. Sex significantly moderated left DG volume (B = -4.26, p = 0.017), such that the association was positive and significant only for males. Total left hippocampal volume [indirect effect = 0.002, 95% CI (0.0002, 0.00), p = 0.027] and right subiculum volume [indirect effect = 0.002, 95% CI (0.0007, 0.01), p = 0.006] statistically mediated the relationship between CRF and episodic memory performance.DiscussionWhile higher CRF was significantly associated with greater total hippocampal volume, CRF was not associated with all underlying subfield volumes. Our results further demonstrate the relevance of the associations between CRF and hippocampal volume for episodic memory performance. Finally, our results suggest that the regionally-specific effects of aging and Alzheimer's disease on hippocampal subfields could be mitigated by maintaining higher CRF in older adulthood.

Dataset Information

Cerebral arterial pulsatility is linked to hippocampal microvascular function and episodic memory in healthy older adults.

Publications

Cerebral arterial pulsatility is linked to hippocampal microvascular function and episodic memory in healthy older adults.

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