Obstructive sleep apnea severity is associated with CSF biomarkers of synaptic dysfunction and neuroinflammation in a cohort at risk for AD.

Background: Obstructive sleep apnea (OSA) is associated with hypoxia‐induced neuronal impairment and dysfunction—key risk factors for the pathogeneses of age‐related neurodegenerative diseases such as Alzheimer‘s disease (AD). This study examined longitudinal associations between OSA severity and CSF biomarkers associated with AD, synaptic dysfunction, and neuroinflammation in a sample of late‐middle‐aged adults with increased risk for AD.

Method: N=25 cognitively unimpaired adults (64% female, mean age 65.

KLOTHO KL‐VS genotype modifies the relationship between cardiorespiratory fitness and CSF biomarkers of neurodegeneration, synaptic dysfunction, and inflammation.

Background: Less adequate cardiorespiratory fitness (CRF) is associated with several aspects of Alzheimer’s disease (AD) pathology, including neuroinflammation, neurodegeneration and synaptic dysfunction, all of which are known contributors to the clinical outcome – progressive cognitive decline [1]. AD‐associated biomolecular changes also seem to be attenuated in carriers of the functionally advantageous variant of the KLOTHO gene (KL‐VS) [2]. While KL‐VS and CRF both appear to mitigate aspects of AD pathology, they have been exclusively studied in isolation.

Cardiorespiratory Fitness Modifies the Association Between Cerebral Pulsatility on Amyloid Burden and Core CSF Biomarkers of Alzheimer’s Disease.

Background: Increasing evidence supports the notion that vascular dysfunction contributes to the evolution of Alzheimer’s disease (AD). Cerebral pulsatility index (PI) is reportedly higher in AD and MCI compared to age matched controls and has been associated with greater beta‐amyloid (Aß) burden. Higher cardiorespiratory fitness (CRF) positively affects vascular function and is associated with lower PI in several large cerebral vessels.

Cardiorespiratory Fitness Modifies the Association of Cerebral Pulsatility on CSF Biomarkers Related to Neurodegeneration, Synaptic Dysfunction, and Neuroinflammation.

Background: Cerebral pulsatility (PI) is reportedly higher in individuals with AD and MCI compared to age matched controls and has been associated with greater beta‐amyloid (Aß) burden, but its relationship to other neurodegenerative biomarkers is unknown. Higher cardiorespiratory fitness (CRF) positively affects vascular function and is associated with lower PI in several large cerebral vessels. The relationship between PI, CRF, and biomarkers for neurodegeneration have not yet been characterized.

Positron emission tomography neuroimaging of [F]fluorodeoxyglucose uptake and related behavior in the -/- rat model of Parkinson disease.

Introduction: Parkinson disease (PD) is a neurodegenerative condition affecting multiple sensorimotor and cognitive systems. The rat model exhibits vocal, cognitive, and limb use deficits seen in idiopathic PD. We sought to measure glucose metabolism in brain regions in and wild type (WT) rats, and to associate these to measures of ultrasonic vocalization, cognition, and limb use behavior.

Misfolded alpha synuclein co-occurrence with Alzheimer's disease proteinopathy.

Introduction: Multi-etiology dementia necessitates in-vivo markers of copathologies including misfolded -synuclein (syn). We measured misfolded syn aggregates (syn-seeds) via qualitative seed amplifcation assays (synSAA) and examined relationships with markers of Alzheimer's disease (AD).

Methods: Cerebrospinal fluid (CSF) was obtained from 420 participants in two Wisconsin AD risk cohorts (35% male; 91% cognitively unimpaired; mean (SD) age, 65.

A longitudinal evaluation of personalized intrinsic network topography and cognitive decline in Parkinson's disease.

Resting state functional magnetic resonance imaging (R-fMRI) offers insight into how synchrony within and between brain networks is altered in disease states. Individual and disease-related variability in intrinsic connectivity networks may influence our interpretation of R-fMRI data. We used a personalized approach designed to account for individual variation in the spatial location of correlation maxima to evaluate R-fMRI differences between Parkinson's disease (PD) patients who showed cognitive decline, those who remained cognitively stable and cognitively stable controls.

Cerebral cortical thickness and cognitive decline in Parkinson's disease.

In Parkinson's disease (PD), reduced cerebral cortical thickness may reflect network-based degeneration. This study performed cognitive assessment and brain MRI in 30 PD participants and 41 controls at baseline and 18 months later. We hypothesized that cerebral cortical thickness and volume, as well as change in these metrics, would differ between PD participants who remained cognitively stable and those who experienced cognitive decline.

AD-associated CSF biomolecular changes are attenuated in KL-VS heterozygotes.

Introduction: Dementia as an inevitable aging consequence has been challenged and underscores the need for investigations of the factors that confer resilience. We examine whether the functionally advantageous KL-VS variant of the putative aging suppressor gene attenuates age-related cognitive decline and deleterious biomolecular changes.

Methods: Trajectories of change in memory and executive function ( = 360; 2-12 visits) and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers-amyloid beta (Aβ)42, total tau (t-tau), phosphorylated tau (p-tau) ( = 112; 2-4 samplings)-were compared between KL-VS non-carriers and heterozygotes in middle-aged and older adults from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center studies.

Cardiorespiratory fitness and cognition in persons at risk for Alzheimer's disease.

Introduction: This study examined the relationship between cardiorespiratory fitness (CRF) and longitudinal cognitive functioning in a cohort enriched with risk factors for Alzheimer's disease (AD).

Methods: A total of 155 enrollees in the Wisconsin Registry for Alzheimer's Prevention completed repeat comprehensive neuropsychological evaluations that assessed six cognitive domains. Peak oxygen consumption (VOpeak) was the primary measure of CRF.

Age-related differences in white matter microstructure measured by advanced diffusion MRI in healthy older adults at risk for Alzheimer's disease.

Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric-fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO-is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer's disease (AD).

Impact of sex and ε4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study.

Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer's disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40-89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with genotype, biological sex, and cardiometabolic measurements.

Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes.

Background: Identification of new genetic variants that modify Alzheimer's disease (AD) risk will elucidate novel targets for curbing the disease progression or delaying symptom onset.

Objective: To examine whether the functionally advantageous KLOTHO gene KL-VS variant attenuates age-related alteration in cerebrospinal fluid (CSF) biomarkers or cognitive function in middle-aged and older adults enriched for AD risk.

Methods: Sample included non-demented adults (N = 225, mean age = 63±8, 68% women) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center who were genotyped for KL-VS, underwent CSF sampling and had neuropsychological testing data available proximal to CSF draw.

Cardiorespiratory Fitness Associates with Cerebral Vessel Pulsatility in a Cohort Enriched with Risk for Alzheimer's Disease.

Background: There is increasing evidence that vascular disease risk factors contribute to evolution of the dementia syndrome of Alzheimer's disease (AD). One important measure of cerebrovascular health is pulsatility index (PI) which is thought to represent distal vascular resistance, and has previously been reported to be elevated in AD clinical syndrome. Physical inactivity has emerged as an independent risk factor for cardiovascular disease.

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

Background: White matter hyperintensities (WMH) are frequently observed on T2-weighted brain magnetic resonance imaging studies of healthy older adults and have been linked with impairments in balance, gait, and cognition. Nonetheless, few studies have investigated the longitudinal effects of comorbid WMH on cognition and motor function in Parkinson's disease.

Methods: The Lesion Segmentation Tool for Statistical Parametric Mapping was used to obtain total lesion volume and map regional WMH probabilities in 29 PD and 42 control participants at two study visits 18 months apart.

Cardiorespiratory Fitness Modifies Influence of Sleep Problems on Cerebrospinal Fluid Biomarkers in an At-Risk Cohort.

Background: Previous studies indicate that cardiorespiratory fitness (CRF) and sleep are each favorably associated with Alzheimer's disease (AD) pathophysiology, including reduced amyloid-β (Aβ) and tau pathology. However, few studies have examined CRF and sleep in the same analysis.

Objective: To examine the relationship between sleep and core AD cerebrospinal fluid (CSF) biomarkers among at-risk healthy late-middle-aged adults and determine whether CRF modifies this association.

heterozygosity attenuates -related amyloid burden in preclinical AD.

Objective: To examine whether the gene variant KL-VS attenuates associated β-amyloid (Aβ) accumulation in a late-middle-aged cohort enriched with Alzheimer disease (AD) risk factors.

Methods: Three hundred nine late-middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center were genotyped to determine KL-VS and status and underwent CSF sampling (n = 238) and/or C-Pittsburgh compound B (PiB)-PET imaging (n = 183). Covariate-adjusted regression analyses were used to investigate whether exerted expected effects on Aβ burden.

Fitness, independent of physical activity is associated with cerebral blood flow in adults at risk for Alzheimer's disease.

Patterns of decreased resting cerebral blood flow (CBF) within the inferior temporal gyri, angular gyri, and posterior cingulate are a feature of aging and Alzheimer's disease (AD) and have shown to be predictive of cognitive decline among older adults. Fitness and physical activity are both associated with many indices of brain health and may positively influence CBF, however, the majority of research to date has examined these measures in isolation, leaving the potential independent associations unknown. The purpose of this study was to determine the unique contributions of fitness and physical activity when predicting CBF in cognitively healthy adults at risk for AD.

Cardiorespiratory fitness attenuates age-associated aggregation of white matter hyperintensities in an at-risk cohort.

Background: Age is the cardinal risk factor for Alzheimer's disease (AD), and white matter hyperintensities (WMH), which are more prevalent with increasing age, may contribute to AD. Higher cardiorespiratory fitness (CRF) has been shown to be associated with cognitive health and decreased burden of AD-related brain alterations in older adults. Accordingly, the aim of this study was to determine whether CRF attenuates age-related accumulation of WMH in middle-aged adults at risk for AD.

In vivo imaging of inflammation and oxidative stress in a nonhuman primate model of cardiac sympathetic neurodegeneration.

Loss of cardiac postganglionic sympathetic innervation is a characteristic pathology of Parkinson's disease (PD). It progresses over time independently of motor symptoms and is not responsive to typical anti-parkinsonian therapies. Cardiac sympathetic neurodegeneration can be mimicked in animals using systemic dosing of the neurotoxin 6-hydroxydopamine (6-OHDA).

Longitudinal white matter microstructural change in Parkinson's disease.

Postmortem studies of Parkinson's disease (PD) suggest that Lewy body pathology accumulates in a predictable topographical sequence, beginning in the olfactory bulb, followed by caudal brainstem, substantia nigra, limbic cortex, and neocortex. Diffusion-weighted imaging (DWI) is sensitive, if not specific, to early disease-related white matter (WM) change in a variety of traumatic and degenerative brain diseases. Although numerous cross-sectional studies have reported DWI differences in cerebral WM in PD, only a few longitudinal studies have investigated whether DWI change exceeds that of normal aging or coincides with regional Lewy body accumulation.

Arterial spin labeling reveals relationships between resting cerebral perfusion and motor learning in Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative disease that produces changes in movement, cognition, sleep, and autonomic function. Motor learning involves acquisition of new motor skills through practice, and is affected by PD. The purpose of the present study was to evaluate regional differences in resting cerebral blood flow (rCBF), measured using arterial spin labeling (ASL) MRI, during a finger-typing task of motor skill acquisition in PD patients compared to age- and gender-matched controls.

Moderate intensity physical activity associates with CSF biomarkers in a cohort at risk for Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is characterized by the presence of amyloid β (Aβ) plaques, neurofibrillary tangles, and neurodegeneration, evidence of which may be detected in vivo via cerebrospinal fluid (CSF) sampling. Physical activity (PA) has emerged as a possible modifier of these AD-related pathological changes. Consequently, the aim of this study was to cross-sectionally examine the relationship between objectively measured PA and CSF levels of Aβ42 and tau in asymptomatic late-middle-aged adults at risk for AD.

Evaluation of striatonigral connectivity using probabilistic tractography in Parkinson's disease.

The cardinal movement abnormalities of Parkinson's disease (PD), including tremor, muscle rigidity, and reduced speed and frequency of movements, are caused by degeneration of dopaminergic neurons in the substantia nigra that project to the putamen, compromising information flow through frontal-subcortical circuits. Typically, the nigrostriatal pathway is more severely affected on the side of the brain opposite (contralateral) to the side of the body that manifests initial symptoms. Several studies have suggested that PD is also associated with changes in white matter microstructural integrity.