Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer's disease

Abstract

Background The fornix is the predominant outflow tract of the hippocampus, a brain region known to be affected early in the course of Alzheimer’s disease (AD). The aims of the present study were to: 1) examine the cross-sectional relationship between fornix DTI measurements (fractional anisotropy (FA), and mean (MD), axial (DA) and radial (DR) diffusivities), hippocampal volume, and memory performance, and 2) compare fornix DTI measures to hippocampal volumes as predictors of progression and transition from amnestic mild cognitive impairment (MCI) to AD dementia. Methods 23 MCI participants with baseline hippocampal volumetry and diffusion tensor imaging received detailed evaluations at baseline, 3, 6, 12 months, and 2.5 years. Six participants converted to AD over the follow-up. Fornix and posterior cingulum DTI measurements and hippocampal volumes were ascertained using manual measures. Random effects models assessed each of the neuroimaging measures as predictors of decline on the MMSE, CDR-Sum of boxes and Memory z-scores; ROC analyses examined the predictive value for conversion to AD. Results There was a significant correlation between fornix FA and hippocampal volumes. However, only the fornix measurements (FA, MD, DR, DA) were cross-sectionally correlated with memory z-scores. Both fornix FA and hippocampal volumes were predictive of memory decline. Individually, fornix FA and MD and hippocampal volumes were very good predictors of progression with likelihood ratios>83, and better than 90% accuracy. Conclusion Fornix FA both cross-sectionally correlated with and longitudinally predicted memory decline and progression to AD. Manually-drawn fornix ROI shows comparable promise to hippocampal volume as a predictive biomarker of progression and warrants replication in a larger study.

Cognitive function is associated with impaired heart rate variability in ageing adults: the Irish longitudinal study on ageing wave one results

“…This is in accordance with previous studies reporting significant associations between HRV and verbal memory recall [35]. The integrity of the fornix, which is the predominant outflow tract of the hippocampus, is predictive of memory performance and progression from MCI to AD [19]. This region is also implicated in autonomic control [6], suggesting that the fornix may form the anatomical location underlying the relationship between HRV and cognition.…”

“…Emerging evidence suggests an association between cognitive impairment and autonomic dysfunction. This relationship may be bidirectional with autonomic dysfunction causing systemic hypotension that leads to cognitive impairment [27], while neurodegenerative processes influence autonomic pathways, causing autonomic dysfunction [19].…”

Age-Related Changes in Diffusion Tensor Imaging Metrics of Fornix Subregions in Healthy Humans

“…The importance of the role of the fornix in memory function is well known, with lesions in both animals [7,8,9] and humans [10,11,12,13,14] producing many memory deficits, with particular impairments in memory formation [for reviews, see [15,16]. Moreover, neuroimaging research suggests that loss of fornix integrity is an early event in Alzheimer's disease and precedes hippocampal volume loss [17]. Deep brain stimulation of the fornix can elicit memory recollection [18], and these findings have driven promising studies aimed at improving memory function in those with early stage Alzheimer's disease [19].…”

The association between functional connectivity and cognition in older adults

“…Study participants completed tests of executive function and memory, both of which decline with age and predict the onset of dementia [27][28][29][30][31].…”