Background: White matter hyperintensities (WMH) show a robust relationship with arterial pressure as well as objective and subjective cognitive functioning. In addition, APOE epsilon 4 carriership... Show moreBackground: White matter hyperintensities (WMH) show a robust relationship with arterial pressure as well as objective and subjective cognitive functioning. In addition, APOE epsilon 4 carriership may influence how arterial pressure affects cognitive functioning.Objective: To determine the role of region-specific WMH burden and APOE epsilon 4 carriership on the relationship between mean arterial pressure (MAP) and cognitive function as well as subjective cognitive decline (SCD).Methods: The sample consisted of 87 cognitively unimpaired middle-aged to older adults aged 50-85. We measured WMH volume for the whole brain, anterior thalamic radiation (ATR), forceps minor, and superior longitudinal fasciculus (SLF). We examined whether WMH burden mediated the relationship between MAP and cognition (i.e., TMT-A score for processing speed; Stroop performance for executive function) as well as SCD (i.e., Frequency of Forgetting (FoF)), and whether APOE epsilon 4 carriership moderated that mediation.Results: WMH burden within SLF mediated the effect of MAP on Stroop performance. Both whole brain and ATR WMH burden mediated the effect of MAP on FoF score. In the MAP-WMH-Stroop relationship, the mediation effect of SLFWMH and the effect of MAP on SLF WMH were significant only in APOE epsilon 4 carriers. In the MAP-WMH-FoF relationship, the effect of MAP on whole brain WMH burden was significant only in epsilon 4 carriers.Conclusion: WMH burden and APOE genotype explain the link between blood pressure and cognitive function and may enable a more accurate assessment of the effect of high blood pressure on cognitive decline and risk for dementia. Show less
Viviano, R.P.; Hayes, J.M.; Pruitt, P.J.; Fernandez, Z.J.; Rooden, S. van; Grond, J. van der; ... ; Damoiseaux, J.S. 2019
Subjective cognitive decline, a perceived worsening of cognitive functioning without objective deficit onassessment, could indicate incipient dementia. However, the neural correlates of subjective... Show moreSubjective cognitive decline, a perceived worsening of cognitive functioning without objective deficit onassessment, could indicate incipient dementia. However, the neural correlates of subjective cognitive decline asassessed by magnetic resonance imaging remain somewhat unclear. Here, we evaluated differences in functionalconnectivity across memory regions, and cognitive performance, between healthy older adults aged 50 to 85 with(n¼35,Age¼68.57.7, 22 female), and without (n¼48,Age¼67.08.8, 29 female) subjective cognitivedecline. We also evaluated neurite density, fractional anisotropy, and mean diffusivity of the parahippocampalcingulum, cingulate gyrus cingulum, and uncinatefiber bundles in a subsample of participants (n¼37). Partic-ipants with subjective cognitive decline displayed lower average functional connectivity across regions of a pu-tative posterior memory system, and lower retrosplenial-precuneus functional connectivity specifically, than thosewithout memory complaints. Furthermore, participants with subjective cognitive decline performed poorer thancontrols on visual working memory. However, groups did not differ in cingulum or uncinate diffusion measures.Our results show differences in functional connectivity and visual working memory in participants with subjectivecognitive decline that could indicate potential incipient dementia. Show less
Rooden, S. van; Berg-Huysmans, A.A. van den; Croll, P.H.; Labadie, G.; Hayes, J.M.; Viviano, R.; ... ; Damoiseaux, J.S. 2018
Background:Research in older adults with subjective cognitive decline (SCD) has mainly focused on Alzheimer’s disease (AD)-related MRI markers, such as hippocampal volume. However, small vessel... Show moreBackground:Research in older adults with subjective cognitive decline (SCD) has mainly focused on Alzheimer’s disease (AD)-related MRI markers, such as hippocampal volume. However, small vessel disease (SVD) is currently established as serious comorbidity in dementia and its preliminary stages. It is therefore important to examine SVD markers in addition to AD markers in older adults presenting with SCD.Objective:The aim of our study was to elucidate the role of SVD markers in late middle-aged to older adults with and without SCD in addition to the commonly found role of AD markers (hippocampal volume).Methods:67 healthy late middle-aged to older adults participated in this study (mean age 68 years); 25 participants with SCD and 42 participants without SCD. We evaluated quantitative as well as qualitative AD markers (i.e., hippocampal volume and medial temporal lobe atrophy (MTA) scale) and SVD markers (i.e., white matter hyperintensities (WMH) volume, Fazekas scale, microbleeds, and lacunar infarcts), and neuropsychological function and amount of memory complaints.Results:We found a significant effect of SCD on hippocampal atrophy, as assessed using the MTA scale, but not on hippocampal volume. In addition, we found a significant effect of SCD, and amount of memory complaints, on WMH volume and Fazekas score, suggesting larger WMH volumes in participants with SCD.Conclusion:SVD MRI markers are related to amount of memory complaints, in addition to the commonly observed AD MRI markers, as demonstrated by the greater WMHs in healthy late middle-aged to older adults with SCD. Show less
Rooden, S. van; Berg-Huysmans, A.A. van den; Croll, P.H.; Labadie, G.; Hayes, J.M.; Viviano, R.; ... ; Damoiseaux, J.S. 2018
Background: Local network connectivity disruptions in Alzheimer's disease patients have been found using graph analysis in BOLD fMRI. Other studies using MEG and cortical thickness measures,... Show moreBackground: Local network connectivity disruptions in Alzheimer's disease patients have been found using graph analysis in BOLD fMRI. Other studies using MEG and cortical thickness measures, however, show more global long distance connectivity changes, both in functional and structural imaging data. The form and role of functional connectivity changes thus remains ambiguous. The current study shows more conclusive data on connectivity changes in early AD using graph analysis on resting-state condition fMRI data. Methodology/Principal Findings: 18 mild AD patients and 21 healthy age-matched control subjects without memory complaints were investigated in resting-state condition with MRI at 1.5 Tesla. Functional coupling between brain regions was calculated on the basis of pair-wise synchronizations between regional time-series. Local (cluster coefficient) and global (path length) network measures were quantitatively defined. Compared to controls, the characteristic path length of AD functional networks is closer to the theoretical values of random networks, while no significant differences were found in cluster coefficient. The whole-brain average synchronization does not differ between Alzheimer and healthy control groups. Post-hoc analysis of the regional synchronization reveals increased AD synchronization involving the frontal cortices and generalized decreases located at the parietal and occipital regions. This effectively translates in a global reduction of functional long-distance links between frontal and caudal brain regions. Conclusions/Significance: We present evidence of AD-induced changes in global brain functional connectivity specifically affecting long-distance connectivity. This finding is highly relevant for it supports the anterior-posterior disconnection theory and its role in AD. Our results can be interpreted as reflecting the randomization of the brain functional networks in AD, further suggesting a loss of global information integration in disease. Show less
