Increased White Matter Aerobic Glycolysis in Multiple Sclerosis.

Objective: Despite treatments which reduce relapses in multiple sclerosis (MS), many patients continue to experience progressive disability accumulation. MS is associated with metabolic disruptions and cerebral metabolic stress predisposes to tissue injury and possibly impaired remyelination. Additionally, myelin homeostasis is metabolically expensive and reliant on glycolysis.

Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease.

Introduction: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.

Methods: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes.

Brain aerobic glycolysis and resilience in Alzheimer disease.

The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aβ) deposition in individuals with symptomatic and preclinical Alzheimer disease (AD). Brain AG decreases with age, but the functional significance of this decrease with regard to the development of AD symptomatology is poorly understood. Using PET measurements of regional blood flow, oxygen consumption, and glucose utilization-from which we derive AG-we find that cognitive impairment is strongly associated with loss of the typical youthful pattern of AG.

Assessment of Instrumental Activities of Daily Living in Preclinical Alzheimer Disease.

Questionnaires are used to assess instrumental activities of daily living (IADL) among individuals with preclinical Alzheimer disease (AD). They have indicated no functional impairment among this population. We aim to determine among cognitively normal (CN) older adults with and without preclinical AD whether: (a) performance-based IADL assessment measures a wider range of function than an IADL questionnaire and (b) biomarkers of AD are associated with IADL performance.

Pattern and implications of neurological examination findings in autosomal dominant Alzheimer disease.

Introduction: As knowledge about neurological examination findings in autosomal dominant Alzheimer disease (ADAD) is incomplete, we aimed to determine the frequency and significance of neurological examination findings in ADAD.

Methods: Frequencies of neurological examination findings were compared between symptomatic mutation carriers and non mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN) to define AD neurological examination findings. AD neurological examination findings were analyzed regarding frequency, association with and predictive value regarding cognitive decline, and association with brain atrophy in symptomatic mutation carriers.

Quantitative Gradient Echo MRI Identifies Dark Matter as a New Imaging Biomarker of Neurodegeneration that Precedes Tisssue Atrophy in Early Alzheimer's Disease.

Background: Currently, brain tissue atrophy serves as an in vivo MRI biomarker of neurodegeneration in Alzheimer's disease (AD). However, postmortem histopathological studies show that neuronal loss in AD exceeds volumetric loss of tissue and that loss of memory in AD begins when neurons and synapses are lost. Therefore, in vivo detection of neuronal loss prior to detectable atrophy in MRI is essential for early AD diagnosis.

Falls: a marker of preclinical Alzheimer disease: a cohort study protocol.

Introduction: Progression to symptomatic Alzheimer disease (AD) occurs slowly over a series of preclinical stages. Declining functional mobility may be an early indicator of loss of brain network integration and may lead to an increased risk of experiencing falls. It is unknown whether measures of functional mobility and falls are preclinical markers of AD.

Cerebrospinal fluid Aβ42 moderates the relationship between brain functional network dynamics and cognitive intraindividual variability.

As Alzheimer's disease (AD) pathology accumulates, resting-state functional connectivity (rs-fc) within and between brain networks decreases, and fluctuations in cognitive performance known as intraindividual variability (IIV) increase. Here, we assessed the relationship between IIV and anticorrelations in rs-fc between the default mode network (DMN)-dorsal attention network (DAN) in cognitively normal older adults and symptomatic AD participants. We also evaluated the relationship between cerebrospinal fluid (CSF) biomarkers of AD (amyloid-beta [Aβ] and tau) and IIV-anticorrelation in rs-fc.

Socioeconomic Status Mediates Racial Differences Seen Using the AT(N) Framework.

Objectives: African Americans are at greater risk for developing Alzheimer's disease (AD) dementia than non-Hispanic whites. In addition to biological considerations (eg, genetic influences and comorbid disorders), social and environmental factors may increase the risk of AD dementia. This paper (1) assesses neuroimaging biomarkers of amyloid (A), tau (T), and neurodegeneration (N) for potential racial differences and (2) considers mediating effects of socioeconomic status (SES) and measures of small vessel and cardiovascular disease on observed race differences.

Falls Associate with Neurodegenerative Changes in ATN Framework of Alzheimer's Disease.

Background: Behavioral markers for Alzheimer's disease (AD) are not included within the widely used amyloid-tau-neurodegeneration framework.

Objective: To determine when falls occur among cognitively normal (CN) individuals with and without preclinical AD.

Methods: This cross-sectional study recorded falls among CN participants (n = 83) over a 1-year period.

Mapping language function with task-based vs. resting-state functional MRI.

Background: Use of functional MRI (fMRI) in pre-surgical planning is a non-invasive method for pre-operative functional mapping for patients with brain tumors, especially tumors located near eloquent cortex. Currently, this practice predominantly involves task-based fMRI (T-fMRI). Resting state fMRI (RS-fMRI) offers an alternative with several methodological advantages.

Relationships between big-five personality factors and Alzheimer's disease pathology in autosomal dominant Alzheimer's disease.

Introduction: Changes in personality characteristics are associated with the onset of symptoms in Alzheimer's disease (AD) and may even precede clinical diagnosis. However, personality changes caused by disease progression can be difficult to separate from changes that occur with normal aging. The Dominantly Inherited Alzheimer Network (DIAN) provides a unique cohort in which to relate measures of personality traits to in vivo markers of disease in a much younger sample than in typical late onset AD.

Physical Exercise and Longitudinal Trajectories in Alzheimer Disease Biomarkers and Cognitive Functioning.

Introduction: Associations of physical exercise with Alzheimer disease (AD) biomarkers and cognitive functioning have been observed cross-sectionally. However, the effects of exercise on longitudinal change in AD biomarkers have not been thoroughly investigated. The current study examined whether individuals with higher baseline exercise exhibited less longitudinal change in AD biomarkers and cognitive functioning, and whether APOE and/or brain-derived neurotrophic factor (BDNF) genotypes moderated the effects of exercise on longitudinal changes.

Sex-related Differences in Tau Positron Emission Tomography (PET) and the Effects of Hormone Therapy (HT).

Importance: Female sex is a major risk factor for late-onset Alzheimer disease (AD), and sex hormones have been implicated as a possible protective factor. Neuroimaging studies that evaluated the effects of sex hormones on brain integrity have primarily emphasized neurodegenerative measures rather than amyloid and tau burden.

Objective: We compared cortical amyloid and regional tau positron emission tomography (PET) deposition between cognitively normal males and females.

Resting State Functional Connectivity Signature Differentiates Cognitively Normal from Individuals Who Convert to Symptomatic Alzheimer's Disease.

Background: Changes in resting state functional connectivity (rs-fc) occur in Alzheimer's disease (AD), but few longitudinal rs-fc studies have been performed. Most studies focus on single networks and not a global measure of rs-fc. Although the amyloid tau neurodegeneration (AT(N)) framework is increasingly utilized by the AD community, few studies investigated when global rs-fc signature changes occur within this model.

Functional connectivity among brain regions affected in Alzheimer's disease is associated with CSF TNF-α in APOE4 carriers.

It is now recognized that understanding how neuroinflammation affects brain function may provide new insights into Alzheimer's pathophysiology. Tumor necrosis factor (TNF)-α, an inflammatory cytokine marker, has been implicated in Alzheimer's disease (AD), as it can impair neuronal function through suppression of long-term potentiation. Our study investigated the relationship between cerebrospinal fluid TNF-α and functional connectivity (FC) in a cohort of 64 older adults (μ age = 69.

Amyloid imaging of dutch-type hereditary cerebral amyloid angiopathy carriers.

Objective: To determine whether amyloid imaging with the positron emission tomography (PET) agent Pittsburgh compound B (PiB) can detect vascular β-amyloid (Aβ) in the essentially pure form of cerebral amyloid angiopathy associated with the Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) mutation.

Methods: PiB retention in a cortical composite of frontal, lateral, and retrosplenial regions (FLR) was measured by PiB-PET in 19 D-CAA mutation carriers (M ; 13 without neurologic symptoms, 6 with prior lobar intracerebral hemorrhage) and 17 mutation noncarriers (M ). Progression of PiB retention was analyzed in a subset of 18 serially imaged individuals (10 asymptomatic M , 8 M ).

MRI safety risks in the obese: The case of the disposable lighter stored in the pannus.

Obese patients constitute 40% of the adult population. MRIs of obese patients are typically challenging because of the effects of a large field of view on image quality and the increased risk of thermal burns from contact with the bore. In this case report, the impacts of obesity on MRI procedures and safety are introduced.

Clinical, pathophysiological and genetic features of motor symptoms in autosomal dominant Alzheimer's disease.

Owing to an early and marked deposition of amyloid-β in the basal ganglia, autosomal dominant Alzheimer's disease could distinctly involve motor symptoms. Therefore, we aimed to assess the prevalence and characteristics of motor signs in autosomal dominant Alzheimer's disease. Baseline Unified Parkinson Disease Rating Scale part three scores (UPDRS-III) from 433 participants of the Dominantly Inherited Alzheimer's Network observational study were analysed.

Tau Positron Emission Tomography Binding Is Not Elevated in HIV-Infected Individuals.

Regional standardized uptake value ratios (SUVRs) for tau positron emission tomography (PET) were compared among 19 cognitively normal human immunodeficiency virus (HIV)-negative control individuals, 20 HIV-negative patients with symptomatic Alzheimer disease, 15 cognitively normal HIV-positive individuals, and 17 cognitively impaired HIV-positive individuals. Among the HIV-positive participants, the correlation between tau PET SUVRs and both HIV loads and CD4+ T-cell counts (recent and nadir). Tau PET SUVRs were similar for HIV-positive individuals and HIV-negative control individuals.

Aerobic glycolysis and tau deposition in preclinical Alzheimer's disease.

Research of the human brain metabolism in vivo has largely focused on total glucose use (via fluorodeoxyglucose positron emission tomography) and, until recently, did not examine the use of glucose outside oxidative phosphorylation, which is known as aerobic glycolysis (AG). AG supports important functions including biosynthesis and neuroprotection but decreases dramatically with aging. This multitracer positron emission tomography study evaluated the relationship between AG, total glucose use (CMRGlc), oxygen metabolism (CMRO), tau, and amyloid deposition in 42 individuals, including those at preclinical and symptomatic stages of Alzheimer's disease.