Sub-Regional Hippocampal Injury is Associated with Fornix Degeneration in Alzheimer’s Disease

We examined in vivo evidence of axonal degeneration in association with neuronal pathology in Alzheimer’s disease (AD) through analysis of fornix microstructural integrity and measures of hippocampal subfield atrophy. Based on known anatomical topography, we hypothesized that the local thickness of subiculum and CA1 hippocampus fields would be associated with fornix integrity, reflecting an association between AD-related injury to hippocampal neurons and degeneration of associated axon fibers. To test this hypothesis, multi-modal imaging, combining measures of local hippocampal radii with diffusion tensor imaging (DTI), was applied to 44 individuals clinically diagnosed with AD, 44 individuals clinically diagnosed with mild cognitive impairment (MCI), and 96 cognitively normal individuals. Fornix microstructural degradation, as measured by reduced DTI-based fractional anisotropy (FA), was prominent in both MCI and AD, and was associated with reduced hippocampal volumes. Further, reduced fornix FA was associated with reduced anterior CA1 and antero-medial subiculum thickness. Finally, while both lesser fornix FA and lesser hippocampal volume were associated with lesser episodic memory, only the hippocampal measures were significant predictors of episodic memory in models including both hippocampal and fornix predictors. The region-specific association between fornix integrity and hippocampal neuronal death may provide in vivo evidence for degenerative white matter injury in AD: axonal pathology that is closely linked to neuronal injury

Age-related slowing of response selection and production in a visual choice reaction time task

Aging is associated with delayed processing in choice reaction time (CRT) tasks, but the processing stages most impacted by aging have not been clearly identified. Here, we analyzed CRT latencies in a computerized serial visual feature-conjunction task. Participants responded to a target letter (probability 40%) by pressing one mouse button, and responded to distractor letters differing either in color, shape, or both features from the target (probabilities 20% each), by pressing the other mouse button. Stimuli were presented randomly to the left and right visual fields and stimulus onset asynchronies (SOAs) were adaptively reduced following correct responses using a staircase procedure. In Experiment 1, we tested 1466 participants who ranged in age from 18 to 65 years. CRT latencies increased significantly with age (r = 0.47, 2.80 ms/year). Central processing time (CPT), isolated by subtracting simple reaction times (obtained in a companion experiment performed on the same day) from CRT latencies, accounted for more than 80% of age-related CRT slowing, with most of the remaining increase in latency due to slowed motor responses. Participants were faster and more accurate when the stimulus location was spatially compatible with the mouse button used for responding, and this effect increased slightly with age. Participants took longer to respond to distractors with target color or shape than to distractors with no target features. However, the additional time needed to discriminate the more target-like distractors did not increase with age. In Experiment 2, we replicated the findings of Experiment 1 in a second population of 178 participants (ages 18-82 years). CRT latencies did not differ significantly in the two experiments, and similar effects of age, distractor similarity, and stimulus-response spatial compatibility were found. The results suggest that the age-related slowing in visual CRT latencies is largely due to delays in response selection and production