Differences in structural MRI and diffusion tensor imaging underlie visuomotor performance declines in older adults with an increased risk for Alzheimer’s disease

Abstract

IntroductionVisuomotor impairments have been demonstrated in preclinical AD in individuals with a positive family history of dementia and APOE e4 carriers. Previous behavioral findings have also reported sex-differences in performance of visuomotor tasks involving a visual feedback reversal. The current study investigated the relationship between grey and white matter changes and non-standard visuomotor performance, as well as the effects of APOE status, family history of dementia, and sex on these brain-behavior relationships.MethodsOlder adults (n = 49) with no cognitive impairments completed non-standard visuomotor tasks involving a visual feedback reversal, plane-change, or combination of the two. Participants with a family history of dementia or who were APOE e4 carriers were considered at an increased risk for AD. T1-weighted anatomical scans were used to quantify grey matter volume and thickness, and diffusion tensor imaging measures were used to quantify white matter integrity.ResultsIn APOE e4 carriers, grey and white matter structural measures were associated with visuomotor performance. Regression analyses showed that visuomotor deficits were predicted by lower grey matter thickness and volume in areas of the medial temporal lobe previously implicated in visuomotor control (entorhinal and parahippocampal cortices). This finding was replicated in the diffusion data, where regression analyses revealed that lower white matter integrity (lower FA, higher MD, higher RD, higher AxD) was a significant predictor of worse visuomotor performance in the forceps minor, forceps major, cingulum, inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF). Some of these tracts overlap with those important for visuomotor integration, namely the forceps minor, forceps major, SLF, IFOF, and ILF.ConclusionThese findings suggest that measuring the dysfunction of brain networks underlying visuomotor control in early-stage AD may provide a novel behavioral target for dementia risk detection that is easily accessible, non-invasive, and cost-effective. The results also provide insight into the structural differences in inferior parietal lobule that may underlie previously reported sex-differences in performance of the visual feedback reversal task.

Bridging Reduced Grip Strength and Altered Executive Function: Specific Brain White Matter Structural Changes in Patients with Alzheimer’s Disease

“…Disruption of the SLF in AD patients can cause hypofunction of the DMN, sensorimotor and frontoparietal cortices, accompanied by decreased motor and executive abilities, 55 as the SLF connects the frontal, parietal, temporal and occipital lobes that are vital for language, visuospatial function and metacognitive function. 56,57 For example, in clinical pre-AD patients with a family history of dementia or carrying APOE e4, damage to the WM integrity of SLF, UF, CC and cingulum serve as an important predictor of poorer visual-motor integration ability, 58 which can impact grip strength performance. 59 MCI patients have more Aβ and tau protein deposition 60 and microstructural WM damage in UF is also related to memory and executive function in AD and amnestic MCI patients.…”

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi‐Cohort Mega‐Analysis

“…Contrary to our hypotheses, APOE ε4 did not have a greater PAD compared to non‐carriers. Of note, the APOE literature is mixed, with some findings revealing a clear effect of APOE on brain volumetrics, 40 while others show no relationship 41 . In 1 recent examination of over 1,100 individuals, examiners showed a differential effect of APOE on brain volume with the ε4 allele based on age, i.e., a paradoxical “protective” effect in individuals <60 years of age 42 that reversed in older age groups.…”

Accelerated Aging after Traumatic Brain Injury: an ENIGMA Multi-Cohort Mega-Analysis

“…Although we hypothesized that APOE ε4 carriers would have a greater PAD compared to non-carriers, our data show no relationship. Of note, the APOE literature is mixed, with some findings revealing a clear effect of APOE on brain volumetrics, 38 while others show no relationship. 39 In one recent examination of over 1100 individuals, examiners showed a differential effect of APOE on brain volume with the ε4 allele based on age, i.e.…”