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Although there is a strong interaction between motor and cognitive functions, intact speech motor control is a crucial yet often\u2010overlooked component of cognitive functioning. Additionally, motor decline can occur independently and may precede the onset of cognitive impairment in neurodegenerative conditions. These impairments can confound measures of higher\u2010order cognition, typically assessed through behavioral performance. Notably, the associations between cognitive performance and biological indices of speech motor production have been largely unexplored. This study is the first to examine cognitive associations of cortical thickness in brain regions implicated in speech motor performance across the adult lifespan, and to investigate whether age\u2010related structural changes in speech motor regions precede those seen in the hippocampus. Our sample included 699 cognitively healthy adults (56% female) spanning 35\u201390\u2009years from the Human Connectome Project (HCP)\u2010Aging dataset. Cognition was estimated using standard neuropsychological assessments including: the Trail Making Task A\/B (TMT), the Rey Auditory Verbal Learning Test (RAVLT), and a cognitive composite score (summating cognitive performance across multiple tasks). Whole\u2010brain T1\u2010 and T2\u2010weighted MRI images were acquired using 3\u2010Tesla scanners across multiple study sites. Structural images were preprocessed using the HCP minimal preprocessed pipelines to reconstruct cortical surfaces. Volume\u2010based estimates including hippocampal volume and total gray matter volume were adjusted for head size using an adjusted measure of estimated Total Intracranial Volume (eTIV). Speech motor regions were investigated relative to well\u2010characterized relationships with hippocampal volume (a hallmark region for memory and cognition and AD\u2010related atrophy). Estimates of cortical thickness were extracted from 14 bilateral speech motor control regions spanning premotor, motor, somatosensory, insular, and prefrontal cortices. Performance across all cognitive tasks and estimates of brain structure were all highly correlated with age. After controlling for the effects of age, greater hippocampal volume remained correlated with better cognitive performance across all cognitive tasks. However, only cognitive associations with greater total gray matter volume survived correction for multiple comparisons. As expected, age associations with hippocampal volume differed between early (\u22120.191%\/year) and late adulthood (\u22120.714%\/year) (<jats:italic>T<\/jats:italic>\u2009=\u20096.179, <jats:italic>p<\/jats:italic>\u2009=\u20090.0002). Age associations with speech motor control regions significantly differed from the associations seen in GMV, mCT, and\/or hippocampal volume across the lifespan (Pcor &lt;\u20090.0001) and during late adulthood when compared separately. Half the speech motor control regions explored showed decelerated estimated percent difference per year from early and late adulthood. Our results suggest that neurocognitive relationships are highly impacted and often confounded by age. The thickness of several speech motor regions was not associated with cognitive performance and can therefore provide a more <jats:italic>intrinsic<\/jats:italic> measure of aging. Additionally, speech motor control regions decline earlier in adulthood than hippocampal volume and may therefore serve as a target and early indicator of AD\u2010related neurodegeneration. This nuanced understanding is critical for refining early diagnostic criteria for neurodegenerative diseases, including AD, and sheds light on the complex interplay between age\u2010related changes, disease pathology, and cognitive decline.<\/jats:p>","DOI":"10.1002\/hbm.70288","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T13:31:09Z","timestamp":1753277469000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Age\u2010Associated Cortical Thinning in Speech Motor Regions Precedes Hippocampal Decline: Implications for Alzheimer's Disease"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5788-9651","authenticated-orcid":false,"given":"Lindsay C.","family":"Hanford","sequence":"first","affiliation":[{"name":"Department of Psychology Harvard University  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Harvard Medical School, Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Salat","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Harvard Medical School, Massachusetts General Hospital  Charlestown Massachusetts USA"},{"name":"Neuroimaging Research for Veterans Center, VA Boston Healthcare System  Jamaica Plain Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Neurology Harvard Medical School, Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marziye","family":"Eshghi","sequence":"additional","affiliation":[{"name":"Athinoula A. 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