TY - JOUR
T1 - Cortical lobar volume reductions associated with homocysteine-related subcortical brain atrophy and poorer cognition in healthy aging
AU - Song, Hyun
AU - Bharadwaj, Pradyumna K.
AU - Raichlen, David A.
AU - Habeck, Christian G.
AU - Grilli, Matthew D.
AU - Huentelman, Matthew J.
AU - Hishaw, Georg A.
AU - Trouard, Theodore P.
AU - Alexander, Gene E.
N1 - Publisher Copyright:
Copyright © 2024 Song, Bharadwaj, Raichlen, Habeck, Grilli, Huentelman, Hishaw, Trouard and Alexander.
PY - 2024
Y1 - 2024
N2 - Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer’s disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging.
AB - Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer’s disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging.
KW - cognitive aging
KW - gray matter atrophy
KW - scaled subprofile model
KW - vascular risk
KW - white matter hyperintensity
UR - http://www.scopus.com/inward/record.url?scp=85201592028&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85201592028&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2024.1406394
DO - 10.3389/fnagi.2024.1406394
M3 - Article
AN - SCOPUS:85201592028
SN - 1663-4365
VL - 16
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
M1 - 1406394
ER -