Basic Science and Pathogenesis.

Background: White matter hyperintensities (WMHs) are increasingly recognized for their role in cognitive decline and the progression of neurodegenerative conditions including Alzheimer's disease (AD). Despite advances in imaging technologies, the exact contribution of WMHs to disease processes remains a subject of ongoing research. This study aims to apply machine learning approaches to determine critical features of AD-related neuropathologies in vivo.

Basic Science and Pathogenesis.

Background: High blood pressure (BP) is one of the twelve modifiable risk factors that contribute to 40% of dementia cases that could be delayed or prevented. Although high BP is associated with cognitive decline and structural brain changes, less is known about the long-term association between variable BP and cognitive/brain changes. This study was designed to examine the relationship between variable BP and longitudinal cognitive, post-mortem neuropathology, white matter hyperintensity (WMH), gray matter (GM) volume, and white matter (WM) volume change over time.

Clinical Manifestations.

Background: Subjective cognitive decline (SCD), or self-perceived declines in memory/cognition in cognitively healthy older adults is linked to increased cognitive decline, neurodegeneration, and white matter hyperintensity (WMH) burden. However, there is no consistent definition of how to classify people with SCD. This study investigated if individual questions in the Cognitive Change Index (CCI) and Everyday Cognition Scale (ECog), commonly used to classify SCD, are associated with brain volume and WMHs to the same degree.

Beyond Hypertension: Examining Variable Blood Pressure's Role in Cognition and Brain Structure.

Objectives: Hypertension or high blood pressure (BP) is one of the 12 modifiable risk factors that contribute to 40% of dementia cases that could be delayed or prevented. Although hypertension is associated with cognitive decline and structural brain changes, less is known about the long-term association between variable BP and cognitive/brain changes. This study examined the relationship between variable BP and longitudinal cognitive, white matter hyperintensity (WMH), gray matter (GM), and white matter (WM) volume change over time and postmortem neuropathology.

Investigating the relationship between sleep disturbances and white matter hyperintensities in older adults on the Alzheimer's disease spectrum.

Introduction: While studies report that sleep disturbance can have negative effects on brain vasculature, its impact on cerebrovascular diseases such as white matter hyperintensities (WMHs) in beta-amyloid-positive older adults remains unexplored.

Methods: Sleep disturbance, WMH burden, and cognition in normal controls (NCs), and individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD), were examined at baseline and longitudinally. A total of 912 amyloid-positive participants were included (198 NC, 504 MCI, and 210 AD).

Beyond Hypertension: Examining Variable Blood Pressure's Role in Cognition and Brain Structure.

Importance: Hypertension is a known risk factor for cognitive decline and structural brain changes in aging and dementia. In addition to high blood pressure (BP), individuals may also experience variable BP, meaning that their BP fluctuates between normal and high. It is currently unclear what the effects of variable BP are on cognition and brain structure.

The influence of APOE status on rate of cognitive decline.

Background: Apolipoprotein (APOE) ɛ4 positivity and subjective cognitive decline (SCD) both increase risk of Alzheimer's disease (AD) development. However, few studies have examined the relationship between SCD and APOE status, especially using longitudinal data. The current study examined whether APOE is associated with the rate of cognitive change in SCD and mild cognitive impairment (MCI).

Differences in Alzheimer's Disease-Related Pathology Profiles Across Apolipoprotein Groups.

The apolipoprotein (APOE) ɛ4 allele is a risk factor for Alzheimer's disease (AD), whereas the ɛ2 allele is thought to be protective against AD. Few studies have examined the relationship between brain pathologies, atrophy, white matter hyperintensities (WMHs) and APOE status in those with the ɛ2ɛ4 genotype and results are inconsistent for those with an ɛ2 allele. Alzheimer's disease neuroimaging participants were divided into 1 of 4 APOE allele profiles (E4 = ɛ4ɛ4 or ɛ3ɛ4; E2 = ɛ2ɛ2 or ɛ2ɛ3; E3 = ɛ3ɛ3; or E24 = ɛ2ɛ4).

Sex differences in risk factors, burden, and outcomes of cerebrovascular disease in Alzheimer's disease populations.

Background: White matter hyperintensities (WMHs) are associated with cognitive decline and progression to mild cognitive impairment (MCI) and dementia. It remains unclear if sex differences influence WMH progression or the relationship between WMH and cognition.

Methods: Linear mixed models examined the relationship between risk factors, WMHs, and cognition in males and females.

White Matter Hyperintensity Trajectories in Patients With Progressive and Stable Mild Cognitive Impairment.

Background And Objectives: White matter hyperintensities (WMH) are pathologic brain changes that are associated with increased age and cognitive decline. However, the association of WMH burden with amyloid positivity and conversion to dementia in people with mild cognitive impairment (MCI) is unclear. The aim of this study was to expand on this research by examining whether change in WMH burden over time differs in amyloid-negative (Aβ-) and amyloid-positive (Aβ+) people with MCI who either remain stable or convert to dementia.

Hippocampal grading provides higher classification accuracy for those in the AD trajectory than hippocampal volume.

Much research has focused on neurodegeneration in aging and Alzheimer's disease (AD). We developed Scoring by Nonlocal Image Patch Estimator (SNIPE), a non-local patch-based measure of anatomical similarity and hippocampal segmentation to measure hippocampal change. While SNIPE shows enhanced predictive power over hippocampal volume, it is unknown whether SNIPE is more strongly associated with group differences between normal controls (NC), early MCI (eMCI), late (lMCI), and AD than hippocampal volume.

Differences in AD-related pathology profiles across APOE groups.

Background: The apolipoprotein (APOE) e4 allele is a known risk factor for Alzheimer's disease (AD), while the e2 allele is thought to be protective against AD. Few studies have examined the relationship between brain pathologies, atrophy, and white matter hyperintensities (WMHs) and APOE status in those with the e2e4 genotype and results are inconsistent for those with an e2 allele.

Methods: We analyzed Alzheimer's Disease Neuroimaging participants that had APOE genotyping and at least one of the following metrics: regional WMH load, ventricle size, hippocampal (HC) and entorhinal cortex (EC) volume, amyloid level (i.

Investigating the relationship between sleep disturbances and white matter hyperintensities in older adults on the Alzheimer's disease spectrum.

Background: While studies report that sleep disturbance can have negative effects on brain vasculature, its impact on cerebrovascular disease such as white matter hyperintensities (WMHs) in beta-amyloid positive older adults remains unexplored.

Methods: Linear regressions, mixed effects models, and mediation analysis examined the crosssectional and longitudinal associations between sleep disturbance, cognition, and WMH burden, and cognition in normal controls (NCs), mild cognitive impairment (MCI), and Alzheimer's disease (AD) at baseline and longitudinally.

Results: People with AD reported more sleep disturbance than NC and MCI.

The use of hippocampal grading as a biomarker for preclinical and prodromal Alzheimer's disease.

Hippocampal changes are associated with increased age and cognitive decline due to mild cognitive impairment (MCI) and Alzheimer's disease (AD). These associations are often observed only in the later stages of decline. This study examined if hippocampal grading, a method measuring local morphological similarity of the hippocampus to cognitively normal controls (NCs) and AD participants, is associated with cognition in NCs, subjective cognitive decline (SCD), early (eMCI), late (lMCI), and AD.

Subjective cognitive decline is a better marker for future cognitive decline in females than in males.

Background: The identification of biomarkers for early detection of Alzheimer's disease (AD) is critical to the development of therapies and interventions targeted at symptom management and tracking the pathophysiology of disease. The endorsement of subjective cognitive decline (SCD) has emerged as a potential indicator of early change in cognitive status that may be predictive of future impairment at a time when measurable declines in neuropsychological performance cannot be detected. While there are numerous findings revealing sex differences in the prevalence of AD, there is a paucity of research examining sex differences in SCD.

Racial differences in white matter hyperintensity burden in older adults.

White matter hyperintensities (WMHs) may be one of the earliest pathological changes in aging. Race differences in WMH burden has been conflicting. This study examined if race influences WMHs and whether these differences are influenced by vascular risk factors.

White matter hyperintensity load varies depending on subjective cognitive decline criteria.

Increased age and cognitive impairment is associated with an increase in cerebrovascular pathology often measured as white matter hyperintensities (WMHs) on MRI. Whether WMH burden differs between cognitively unimpaired older adults with subjective cognitive decline (SCD +) and without subjective cognitive decline (SCD -) remains conflicting, and could be related to the methods used to identify SCD. Our goal was to examine if four common SCD classification methods are associated with different WMH accumulation patterns between SCD + and SCD - .

Subjective Cognitive Decline Is Associated With Lower Baseline Cognition and Increased Rate of Cognitive Decline.

Objectives: Subjective cognitive decline (SCD) is a known risk factor for Alzheimer's disease. However, little research has examined whether healthy older adults with SCD (SCD+) exhibit lower cognition and increased rates of cognitive decline compared to those without SCD (SCD-). The goal of this study was to examine if cognitive change over a 15-year period differs between SCD+ and SCD-.

Topographical differences in white matter hyperintensity burden and cognition in aging, MCI, and AD.

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).

White matter lesions may be an early marker for age-related cognitive decline.

Background: Research suggests that cerebral small vessel disease (CSVD), amyloid, and pTau contribute to age-related cognitive decline. It remains unknown how these factors relate to one another and how they jointly contribute to cognitive decline in normal aging. This project examines the association between these factors and their relationship to cognitive decline in cognitively unimpaired older adults without subjective cognitive decline.

Regional brain atrophy and cognitive decline depend on definition of subjective cognitive decline.

Background: People with subjective cognitive decline (SCD) may be at increased risk for Alzheimer's disease (AD). However, not all studies have observed this increased risk. This project examined whether four common methods of defining SCD yields different patterns of atrophy and future cognitive decline between cognitively normal older adults with (SCD+ ) and without SCD (SCD-).

Event-Related Potential Measures of the Passive Processing of Rapidly and Slowly Presented Auditory Stimuli in MCI.

Much research effort is currently devoted to the development of a simple, low-cost method to determine early signs of Alzheimer's disease (AD) pathology. The present study employs a simple paradigm in which event-related potentials (ERPs) were recorded to a single auditory stimulus that was presented rapidly or very slowly while the participant was engaged in a visual task. A multi-channel EEG was recorded in 20 healthy older adults and 20 people with mild cognitive impairment (MCI).

Event-related potential evidence that very slowly presented auditory stimuli are passively processed differently in younger and older adults.

The occurrence of a very infrequent and unattended auditory stimulus is highly salient and may result in an interruption of the frontoparietal network controlling processing priorities. Research has suggested that older adults may be unable to compute the level of salience of unattended stimulus inputs. A multi-channel EEG was recorded in 20 younger adults and 20 older adults.

The influence of different types of auditory change on processes associated with the switching of attention in younger and older adults.

Potentially highly relevant but unattended auditory stimuli may result in attention capture. The detection of stimulus change is associated with two event-related potentials: the deviant-related negativity (DRN), whose amplitude varies with the extent of change, and the P3a, which is elicited only by stimuli deemed to be highly relevant. In the present study, younger adults (aged 18-30 years) and older adults (aged 65-73 years) were presented with to-be-ignored auditory stimuli while engaged in a visual task.