Basic Science and Pathogenesis.

Background: APOE4 carriers exhibit cerebrovascular dysfunction which may contribute to the development of cognitive decline and dementia; however, the mechanisms underlying this pathophysiology remain unknown. Impaired cerebrovascular reactivity (CVR) may be associated with vascular injury, inflammation, and endothelial dysfunction. To examine whether these processes may be involved in CVR deficits in APOE4 carriers, we explored whether plasma levels of vascular injury markers indicative of inflammation and endothelial dysfunction are associated with impaired CVR to hypercapnia and hypocapnia in older APOE4 carriers.

Basic Science and Pathogenesis.

Background: Optimal cerebral blood flow is crucial to maintaining cognitive function. Cerebrovascular reactivity (CVR) is a dynamic measure of cerebrovascular function which represents the ability of cerebral blood vessels to regulate blood flow in response to vasoactive stimuli. Prior studies have demonstrated an association between impaired CVR and cognitive function in cerebrovascular and neurodegenerative conditions, including cerebral amyloid angiopathy and Alzheimer disease.

Locus coeruleus MRI contrast, cerebral perfusion, and plasma Alzheimer's disease biomarkers in older adults.

The locus coeruleus (LC) is among the first brain structures impacted by Alzheimer's disease (AD), and noradrenergic denervation may contribute to early neurovascular dysfunction in AD. Mechanistic links between the LC and cerebral perfusion have been demonstrated in rodents, but there have been no similar studies in aging humans. Community-dwelling older adults with no history of stroke or dementia (N=66) underwent structural (T1-MPRAGE; T1-FSE) and perfusion (resting pCASL) MRI.

Spontaneous cerebrovascular reactivity at rest in older adults with and without mild cognitive impairment and memory deficits.

Introduction: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.

Methods: One hundred sixty-one older adults free of dementia or major neurological/psychiatric disorders were recruited.

Spontaneous cerebrovascular reactivity at rest in older adults with and without mild cognitive impairment and memory deficits.

Background: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.

Methods: 161 older adults free of dementia or major neurological/psychiatric disorders were recruited.

Short-term blood pressure variability and brain functional network connectivity in older adults.

Background: Blood pressure variability is increasingly linked with cerebrovascular disease and Alzheimer's disease, independent of mean blood pressure levels. Elevated blood pressure variability is also associated with attenuated cerebrovascular reactivity, which may have implications for functional hyperemia underpinning brain network connectivity. It remains unclear whether blood pressure variability is related to functional network connectivity.

Blood-Derived Progenitor Cells Are Depleted in Older Adults with Cognitive Impairment: A Role for Vascular Resilience?

Background: Depletion of blood-derived progenitor cells, including so called "early endothelial progenitor cells", has been observed in individuals with early stage Alzheimer's disease relative to matched older control subjects. These findings could implicate the loss of angiogenic support from hematopoietic progenitors or endothelial progenitors in cognitive dysfunction.

Objective: To investigate links between progenitor cell proliferation and mild levels of cognitive dysfunction.

Blood pressure variability and plasma Alzheimer's disease biomarkers in older adults.

Blood pressure variability is an emerging risk factor for Alzheimer's disease in older adults, independent of average blood pressure levels. Growing evidence suggests increased blood pressure variability is linked to Alzheimer's disease pathophysiology indexed by cerebrospinal fluid and positron emission tomography markers, but relationships with plasma Alzheimer's disease markers have not been investigated. In this cross-sectional study of 54 community-dwelling older adults (aged 55-88, mean age 69.

Older Adults With Higher Blood Pressure Variability Exhibit Cerebrovascular Reactivity Deficits.

Background: Elevated blood pressure (BP) variability is predictive of increased risk for stroke, cerebrovascular disease, and other vascular brain injuries, independent of traditionally studied average BP levels. However, no studies to date have evaluated whether BP variability is related to diminished cerebrovascular reactivity, which may represent an early marker of cerebrovascular dysfunction presaging vascular brain injury.

Methods: The present study investigated BP variability and cerebrovascular reactivity in a sample of 41 community-dwelling older adults (mean age 69.

Selective vulnerability of medial temporal regions to short-term blood pressure variability and cerebral hypoperfusion in older adults.

Blood pressure variability is an emerging risk factor for stroke, cognitive impairment, and dementia, possibly through links with cerebral hypoperfusion. Recent evidence suggests visit-to-visit (e.g.

Patterns of longitudinal cortical atrophy over 3 years in empirically derived MCI subtypes.

Objective: We previously identified 4 empirically derived mild cognitive impairment (MCI) subtypes via cluster analysis within the Alzheimer's Disease Neuroimaging Initiative (ADNI) and demonstrated high correspondence between patterns of cortical thinning at baseline and each cognitive subtype. We aimed to determine whether our MCI subtypes demonstrate unique longitudinal atrophy patterns.

Methods: ADNI participants (295 with MCI and 134 cognitively normal [CN]) underwent annual structural MRI and neuropsychological assessments.

Fear conditioning, safety learning, and sleep in humans.

Fear conditioning is considered an animal model of post-traumatic stress disorder. Such models have shown fear conditioning disrupts subsequent rapid eye movement sleep (REM). Here, we provide a translation of these models into humans.