• J. Neurol. Neurosurg. Psychiatr. · Jul 2024

    Rates of cortical thinning in Alzheimer's disease signature regions associate with vascular burden but not with β-amyloid status in cognitively normal adults at age 70.

    • Sarah E Keuss, William Coath, David M Cash, Josephine Barnes, Jennifer M Nicholas, Christopher A Lane, Thomas D Parker, Ashvini Keshavan, Sarah M Buchanan, Aaron Z Wagen, Mathew Storey, Matthew Harris, Kirsty Lu, Sarah-Naomi James, Rebecca Street, Ian B Malone, Carole H Sudre, David L Thomas, John C Dickson, Frederik Barkhof, Heidi Murray-Smith, Andrew Wong, Marcus Richards, Nick C Fox, and Jonathan M Schott.
    • Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.
    • J. Neurol. Neurosurg. Psychiatr. 2024 Jul 15; 95 (8): 748752748-752.

    BackgroundConsistent patterns of reduced cortical thickness have been identified in early Alzheimer's disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear.MethodsParticipants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations of baseline cerebral β-amyloid (Aβ) deposition, measured using florbetapir positron emission tomography, and baseline white matter hyperintensity volume (WMHV) on MRI, a marker of cerebral small vessel disease, with subsequent longitudinal changes in AD signature cortical thickness quantified from baseline and repeat MRI (mean [SD] interval 2.4 [0.2] years).ResultsIn a population-based sample of 337 cognitively normal older white adults (mean [SD] age at baseline 70.5 [0.6] years; 48.1% female), higher global WMHV at baseline related to faster subsequent rates of cortical thinning in both AD signature regions (~0.15%/year faster per 10 mL additional WMHV), whereas baseline Aβ status did not. Among Aβ positive participants (n=56), there was some evidence that greater global Aβ standardised uptake value ratio at baseline related to faster cortical thinning in the AD signature Mayo region, but this did not reach statistical significance (p=0.08).ConclusionsCortical thinning within AD signature regions may develop via cerebrovascular pathways. Perhaps reflecting the age of the cohort and relatively low prevalence of Aβ-positivity, robust Aβ-related differences were not detected. Longitudinal follow-up incorporating additional biomarkers will allow assessment of how these relationships evolve closer to expected dementia onset.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

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