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Cumulative Blood Pressure Exposure, Basal Ganglia, and Thalamic Morphology in Midlife.

ABSTRACT: High blood pressure (BP) negatively affects brain structure and function. Hypertension is associated with white matter hyperintensities, cognitive and mobility impairment in late-life. However, the impact of BP exposure from young adulthood on brain structure and function in mid-life is unclear. Identifying early brain structural changes associated with BP exposure, before clinical onset of cognitive dysfunction and mobility impairment, is essential for understanding mechanisms and developing interventions. We examined the effect of cumulative BP exposure from young adulthood on brain structure in a substudy of 144 (61 female) individuals from the CARDIA (Coronary Artery Risk Development in Young Adults) study. At year 30 (Y₃₀, ninth visit), participants (56±4 years old) completed brain magnetic resonance imaging and gait measures (pace, rhythm, and postural control). Cumulative systolic and diastolic BP (cumulative systolic blood pressure, cDBP) over 9 visits were calculated, multiplying mean values between 2 consecutive visits by years between visits. Surface-based analysis of basal ganglia and thalamus was achieved using FreeSurfer-initiated Large Deformation Diffeomorphic Metric Mapping. Morphometric changes were regressed onto cumulative BP to localize regions of shape variation. Y₃₀ white matter hyperintensity volumes were small and positively correlated with cumulative BP but not gait. Negative morphometric associations with cumulative systolic blood pressure were seen in the caudate, putamen, nucleus accumbens, pallidum, and thalamus. A concave right medial putamen shape mediated the relationship between cumulative systolic blood pressure and stride width. Basal ganglia and thalamic morphometric changes, rather than volumes, may be earlier manifestation of gray matter structural signatures of BP exposure that impact midlife gait.

SUBMITTER: Jenkins LM

PROVIDER: S-EPMC8189649 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHigh blood pressure (BP) is a known risk factor for mobility and cognitive impairment in older adults. This study tested the association of cumulative BP exposure from young adulthood to midlife with gait and cognitive function in midlife. Furthermore, we tested whether these associations were modified by cerebral white matter hyperintensity (WMH) burden.MethodsWe included 191 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults), a community-based cohort of young individuals followed over 30 years. Cumulative BP was calculated as the area under the curve (mm?Hg×years) from baseline up to year 30 examination. Gait and cognition were assessed at the year 30 examination. Cerebral WMH was available at year 30 in a subset of participants (n=144) who underwent magnetic resonance imaging. Multiple linear regression models were used to assess the association of cumulative BP exposure with gait and cognition. To test effect modification by WMH burden, participants were stratified at the median of WMH and tested for interaction.ResultsHigher cumulative systolic and diastolic BPs were associated with slower walking speed (both P=0.010), smaller step length (P=0.011 and 0.005, respectively), and higher gait variability (P=0.018 and 0.001, respectively). Higher cumulative systolic BP was associated with lower cognitive performance in the executive (P=0.021), memory (P=0.015), and global domains (P=0.010), and higher cumulative diastolic BP was associated with lower cognitive performance in the memory domain (P=0.012). All associations were independent of socio-demographics and vascular risk factors (body mass index, smoking, diabetes mellitus and total cholesterol). The association between cumulative BP and gait was moderated by WMH burden (interaction P<0.05). However, the relation between cumulative BP and cognitive function was not different based on the WMH burden (interaction P>0.05).ConclusionsExposure to higher BP levels from young to midlife is associated with worse gait and cognitive performance in midlife. Furthermore, WMH moderates the association of cumulative BP exposure with gait, but not with cognitive function in midlife. The mechanisms underpinning the impact of BP exposure on brain structure and function must be investigated in longitudinal studies using a life course approach.

Project description:Schizophrenia is characterized by hypoconnectivity or decreased intrinsic functional connectivity (iFC) between prefrontal-limbic cortices and thalamic nuclei, as well as hyperconnectivity or increased iFC between primary-sensorimotor cortices and thalamic nuclei. However, cortico-thalamic iFC overlaps with larger, structurally defined cortico-striato-pallido-thalamo-cortical (CSPTC) circuits. If such an overlap is relevant for intrinsic hypo-/hyperconnectivity, it suggests (i) that patterns of cortico-subcortical hypo-/hyperconnectivity extend consistently from thalamus to basal ganglia nuclei; and (ii) such consistent hypo-/hyperconnectivity might link distinctively but consonant with different symptom dimensions, namely cognitive and psychotic impairments. To test this hypothesis, 57 patients with schizophrenia and 61 healthy controls were assessed by resting-state functional magnetic resonance imaging (fMRI) and clinical-behavioral testing. IFC from intrinsic cortical networks into thalamus, striatum, and pallidum was estimated by partial correlations between fMRI time courses. In patients, the salience network covering prefrontal-limbic cortices was hypoconnected with the mediodorsal thalamus and ventral parts of striatum and pallidum; these iFC-hypoconnectivity patterns were correlated both among each other and specifically with patients' impaired cognition. In contrast, the auditory-sensorimotor network covering primary-sensorimotor cortices was hyperconnected with the anterior ventral nucleus of the thalamus and dorsal parts of striatum and pallidum; these iFC-hyperconnectivity patterns were likewise correlated among each other and specifically with patients' psychotic symptoms. The results demonstrate that prefrontal-limbic hypoconnectivity and primary-sensorimotor hyperconnectivity extend consistently across subcortical nuclei and specifically across distinct symptom dimensions. Data support the model of consistent cortico-subcortical hypo-/hyperconnectivity within CSPTC circuits in schizophrenia.

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Cumulative Blood Pressure Exposure, Basal Ganglia, and Thalamic Morphology in Midlife.

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