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Dementia risk and thalamic nuclei volumetry in healthy midlife adults: the PREVENT Dementia study.

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Peer-reviewed

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Authors

Dounavi, Maria-Eleni  ORCID logo  https://orcid.org/0000-0001-8287-346X
Lawlor, Brian 
Naci, Lorina 

Abstract

A reduction in the volume of the thalamus and its nuclei has been reported in Alzheimer's disease, mild cognitive impairment and asymptomatic individuals with risk factors for early-onset Alzheimer's disease. Some studies have reported thalamic atrophy to occur prior to hippocampal atrophy, suggesting thalamic pathology may be an early sign of cognitive decline. We aimed to investigate volumetric differences in thalamic nuclei in middle-aged, cognitively unimpaired people with respect to dementia family history and apolipoprotein ε4 allele carriership and the relationship with cognition. Seven hundred participants aged 40-59 years were recruited into the PREVENT Dementia study. Individuals were stratified according to dementia risk (approximately half with and without parental dementia history). The subnuclei of the thalamus of 645 participants were segmented on T1-weighted 3 T MRI scans using FreeSurfer 7.1.0. Thalamic nuclei were grouped into six regions: (i) anterior, (ii) lateral, (iii) ventral, (iv) intralaminar, (v) medial and (vi) posterior. Cognitive performance was evaluated using the computerized assessment of the information-processing battery. Robust linear regression was used to analyse differences in thalamic nuclei volumes and their association with cognitive performance, with age, sex, total intracranial volume and years of education as covariates and false discovery rate correction for multiple comparisons. We did not find significant volumetric differences in the thalamus or its subregions, which survived false discovery rate correction, with respect to first-degree family history of dementia or apolipoprotein ε4 allele status. Greater age was associated with smaller volumes of thalamic subregions, except for the medial thalamus, but only in those without a dementia family history. A larger volume of the mediodorsal medial nucleus (Pfalse discovery rate = 0.019) was associated with a faster processing speed in those without a dementia family history. Larger volumes of the thalamus (P = 0.016) and posterior thalamus (Pfalse discovery rate = 0.022) were associated with significantly worse performance in the immediate recall test in apolipoprotein ε4 allele carriers. We did not find significant volumetric differences in thalamic subregions in relation to dementia risk but did identify an interaction between dementia family history and age. Larger medial thalamic nuclei may exert a protective effect on cognitive performance in individuals without a dementia family history but have little effect on those with a dementia family history. Larger volumes of posterior thalamic nuclei were associated with worse recall in apolipoprotein ε4 carriers. Our results could represent initial dysregulation in the disease process; further study is needed with functional imaging and longitudinal analysis.

Description

Acknowledgements: The authors acknowledge the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The authors thank the PREVENT Dementia participants.


Funder: National Institute for Health; DOI: https://doi.org/10.13039/100000002


Funder: Alzheimer’s Society; DOI: https://doi.org/10.13039/501100000320


Funder: Alzheimer’s Association; DOI: https://doi.org/10.13039/100000957


Funder: Oxford Health Biomedical Research Centre


Funder: Medical Research Council; DOI: https://doi.org/10.13039/501100000265


Funder: NIHR; DOI: https://doi.org/10.13039/501100000272


Funder: NIHR Cambridge Biomedical Research Centre; DOI: https://doi.org/10.13039/501100018956

Keywords

neuroimaging biomarkers, preclinical dementia, thalamic segmentation, volumetric analysis

Journal Title

Brain Commun

Conference Name

Journal ISSN

2632-1297
2632-1297

Volume Title

6

Publisher

Oxford University Press (OUP)
Sponsorship
MRC (via University of Oxford) (MR/T033371/1)