Effects of regional white matter hyperintensities and β-amyloid on domain-specific cognition and progression to dementia.

Pattern of regional white matter hyperintensity volume in mild cognitive impairment subtypes and associations with decline in daily functioning

Differential effects of white matter hyperintensities and regional amyloid deposition on regional cortical thickness

Objective: Late-life depression (LLD) is associated with greater risk of suicide and white matter hyperintensity (WMH), which is also found in suicide attempter (SA) regardless of age. Greater periventricular WMH is related to worse cognitive function. We investigated the spatial distribution of WMH in suicide attempters with LLD and its association with cognitive function. Methods: We recruited 114 participants with LLD (34 with history of suicide attempt and 80 without) and 47 elderly controls (individuals without LLD or history of suicide attempt). Suicide attempters were also classified as early and late life SA (using 55 as median age). WMH was quantified by an automated segmentation algorithm and was classified into different regions including juxtaventricular, periventricular, deep, and juxtacortical WMH. We used analysis of covariance and generalized linear model to compare group differences in WMH (global and regional) and its association with neurocognitive function. Results: Suicide attempters with LLD had significantly higher global WMH (F3, 150 = 2.856, p = 0.039) and periventricular WMH (F3, 150 = 3.635, p=0.014) compared to other groups. This difference was primarily in early-life SAs compared to late-life. There was a significant interaction between global WMH and suicide attempt history on executive function, where SAs with high WMH had lower executive function. Conclusion: Individuals with LLD and a history of suicide attempt had greater WMH (primarily in periventricular WMH) compared to others without. WMH in SAs was associated with reduced executive function and may be an underlying mechanism for cognitive decline in older adults with suicidality. Funding Statement: This study was supported by funding from Supported by (1) medical research grants CMRPG3C0041/42 from Chang Gung Memorial Hospital and NRRPG2H0031 from Ministry of Science and Technology, Taiwan to Chemin Lin (2) NMRPG3G6031/32 and NMRPG3J0121 from Ministry of Science and Technology, Taiwan to Shwu-Hua, Lee (3) the KKHo International Charitable Foundation to Tatia Lee. Declaration of Interests: All authors declare that no support, financial or otherwise, has been received from any organization that may have an interest in the submitted work; and (ii) there are no other relationships or activities that could appear to have influenced the submitted work. Ethics Approval Statement: This project was approved by the ethics committee of the Chang Gung Memorial Hospital Institutional Review Board (IRB: 201601753B0C102).

Regional white matter hyperintensities in posterior cortical atrophy and logopenic progressive aphasia

To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. The Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden. Cardiovascular risk profiles were not predictive of progression in CSF β₄₂-amyloid, [¹⁸F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4. Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway.

Serum Arachidonic Acid Oxylipins Indicate Small Vessel Injury And the Related Executive Function Decline In Stroke Patients

Cross-sectional and longitudinal associations between total and regional white matter hyperintensity volume and cognitive and motor function in Parkinson's disease.

Suicide among older adults represents a major public health concern and is closely associated with late-life depression (LLD). White matter hyperintensities (WMHs), frequently observed in the aging population, have been linked to both LLD and cognitive impairment. However, the role of WMH burden and cognitive dysfunction in older adults with LLD who have recently attempted suicide remains unclear. This study aims to investigate differences in WMH burden and cognitive performance across three groups: LLD patients with a recent suicide attempt (recent suicide attempt group, RSA), non-suicidal LLD patients (non-suicidal group, NS), and healthy older adults (healthy comparison group, HC). We further examine whether the relationship between WMH load and cognitive function varies by suicide attempt status. This cross-sectional study included 58 adults aged 65 years and older. Participants were categorized into three groups: RSA (n = 17), NS (n = 20), and HC (n = 21). All participants underwent brain MRI and completed multiple psychological evaluations and neurocognitive tests, including the Cognitive Abilities Screening Instrument. We compared the three groups with respect to cognitive function, WMHs, and the relationship between WMH load and cognitive performance. LLD patients with a recent suicide attempt (RSA) had significantly poorer global cognitive function and greater periventricular WMH compared to non-suicidal LLD patients and healthy controls. Greater WMH was significantly associated with lower cognitive function only in the suicide-attempt group. Worse global cognitive function and greater WMHs may collectively increase the risk of suicidal attempts in LLD patients.

Greater white matter hyperintensities and the association with executive function in suicide attempters with late-life depression

White matter hyperintensities (WMHs) are pathological changes that occur with increased age and are associated with cognitive decline. Most WMH research has not examined regional differences and focuses on a whole-brain approach. This study examined regional WMHs between normal controls (NCs), people with mild cognitive impairment (MCI), and Alzheimer's disease (AD). We also examined whether WMHs were associated with cognitive decline. Participants from the Alzheimer's Disease Neuroimaging Initiative were included if they had at least one WMH measurement and cognitive scores examining global cognition, executive functioning, and memory. Only amyloid-positive MCI and AD participants were included. A total of 1573 participants with 7381 timepoints over a maximum period of 13years were included. Linear mixed-effects models examined group differences in WMH burden and associations between WMH burden and cognition. People with MCI and AD had increased total and regional WMHs compared to NCs. An association between WMHs and cognition was observed for global cognition, executive functioning, and memory in NCs in all regions. A steeper decline (stronger association between WMH and cognition) was observed in MCI compared to NCs for all cognitive domains in all regions. A steeper decline was observed in AD compared to NCs for global cognition in only the temporal region. A strong association is observed between all cognitive domains of interest and WMH burden in healthy aging and MCI, while those with AD only had a few associations between WMH and global cognition. These findings suggest that the WMH burden is associated with changes in cognition in healthy aging and early cognitive decline.

Greater white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are seen with transactive response DNA-binding protein 43 (TDP-43) pathology in frontotemporal lobar degeneration (FTLD-TDP). WMH associations with TDP-43 pathology in Alzheimer's disease (AD-TDP) remain unclear. A total of 157 participants from Mayo Clinic Rochester with autopsy-confirmed AD, known TDP-43 status, and antemortem fluid-attenuated inversion recovery (FLAIR) MRI were included. Vascular risk factors were assessed. A semi-automated WMH segmentation-quantification process produced total and regional WMH volumes. Penalized linear regression models adjusting for age at MRI analyzed TDP-43 associations (status and typing) with WMHs. TDP-43-positive status was not associated with WMH burden overall because opposite effects were seen based on AD-TDP typing. Despite similar antemortem vascular risk factors and postmortem vascular pathologies, AD-TDP type-α showed greater total and regional WMH burden (particularly in subcortical frontotemporal and basal ganglia regions) than TDP-43 negatives and AD-TDP type-β. AD-TDP types may have different WMH pathomechanisms, with type-α having associations more like FTLD-TDP than AD. In transactive response DNA-binding protein 43 (TDP-43) pathology in Alzheimer's disease (AD-TDP), TDP-43 status alone is not associated with total or regional WMH burden AD-TDP type-α shows greater total, frontotemporal subcortical, and basal ganglia white matter hyperintensities (WMHs) AD-TDP type-β shows less total and subcortical occipital WMHs AD-TDP type-α effect on WMH burden closely mimics the effects of frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) rather than AD Different relationships of AD-TDP types with WMHs suggest different pathomechanisms.

Pathways linking regional hyperintensities in the brain and slower gait

Introduction: Depression in the elderly can have a different pathophysiology and clinical profile, and studies have shown pathological changes in the brain on radio imaging. The present study aimed to find out the association of white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) with the severity of illness and cognition in elderly depressed patients. Methodology: This cross-sectional study included 68 elderly (>60 years of age) depressed patients who had undergone MRI at a tertiary care center, and based on the severity of WMH, they were divided into two groups: no or slight WMH group and moderate or severe WMH group. The severity of depression was assessed using the Hamilton Depression Rating Scale (HAM-D) scale, and neuropsychological assessments were made for testing attention, concentration and executive function. Results: HAM-D scores were found significantly higher in patients with moderate-to-severe WMH groups (22.6 ± 5.2) compared to those with no or slight WMH (16.3 ± 4.2). The cognitive performance evaluated by backward digit span test, Trail making Test A and B, and Color Stroop test was significantly poor in the moderate-to-severe WMH group. Conclusion: Elderly depressed patients having a greater WMH had more severe depression and poor cognitive performance, especially psychomotor and executive functioning. WMH could be a potential marker for the severity of illness and cognition in depression in elderly persons.

LOW GLUCOSE UTILIZATION AND HIGH LACTATE PRODUCTION IN THE ALZHEIMER'S DISEASE BRAIN

The association between white matter hyperintensities and executive decline in mild cognitive impairment is network dependent