Development, validation and application of a new fornix template for studies of aging and preclinical Alzheimer's disease

Abstract

We developed a merged younger-older adult template of the fornix and demonstrated its utility for studies of aging and preclinical Alzheimer's disease (AD). In Experiment 1, probabilistic tractography was used to reconstruct the fornix in younger and older adults and successful streamlines were then averaged to create a merged template in standard space. The new template includes the majority of the fornix from the hippocampal formation to the subcallosal region and the thalamus/hypothalamus. In Experiment 2, the merged template was validated as an appropriate measure for studies of aging, with comparisons against manual tracing measures indicating identical spatial coverage in younger and older adult groups. In Experiment 3, the merged template was found to outperform age-specific templates in measures of sensitivity and specificity computed on diffusion tensor imaging data of an independent participant cohort. In Experiment 4, relevance to preclinical AD was demonstrated via associations between fractional anisotropy within the new fornix template and cerebrospinal fluid markers of AD pathology (Aβ42 and the t-tau/Aβ42 ratio) in a third independent cohort of cognitively normal older adults. Our new template provides an appropriate measure for use in future studies seeking to characterize microstructural alterations in the fornix associated with aging and preclinical AD.

Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease

“…Although the instability of the fornix is well‐described in AD, it is unclear if alterations at the microstructural level are observable in relation to pathological burden in cognitively healthy individuals. Contradictory results have been reported in relation to Aβ: both a lower (Brown et al, ; Gold et al, ) and greater (Racine et al, ) fractional anisotropy in the fornix have been associated with Aβ burden. CSF tau concentration has been associated with lower mean diffusivity in white matter adjacent to the hippocampus (Bendlin et al, ).…”

New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders

“…The T1 data were acquired and pre-processed centrally by UKB. The brain regions were defined by combining the Harvard-Oxford cortical and subcortical atlases 78 (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/Atlases) and the Diedrichsen cerebellar atlas 79 (http://www.diedrichsenlab.org/imaging/propatlas.htm). FAST (FMRIB's Automated Segmentation Tool) 80 was then used to estimate the grey matter partial volume within each brain region.…”

Genome-wide association and functional studies identify 46 novel loci for alcohol consumption and suggest common genetic mechanisms with neuropsychiatric disorders

“…The T1 data were acquired and pre-processed centrally by UKB. The brain regions were defined by combining the Harvard-Oxford cortical and subcortical atlases 74 (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/Atlases) and the Diedrichsen cerebellar atlas 75 (http://www.diedrichsenlab.org/imaging/propatlas.htm). FAST (FMRIB’s Automated Segmentation Tool) 76 was then used to estimate the grey matter partial volume within each brain region.…”