Mapping the impact of age and APOE risk factors for late onset Alzheimer's disease on long range brain connections through multiscale bundle analysis.

Alzheimer's disease currently has no cure and is usually detected too late for interventions to be effective. In this study we have focused on cognitively normal subjects to study the impact of risk factors on their long-range brain connections. To detect vulnerable connections, we devised a multiscale, hierarchical method for spatial clustering of the whole brain tractogram and examined the impact of age and APOE allelic variation on cognitive abilities and bundle properties including texture e.

Racial Disparities in Low-Value Care in the Last Year of Life for Medicare Beneficiaries With Neurodegenerative Disease.

Background And Objectives: There are racial disparities in health care services received by patients with neurodegenerative diseases, but little is known about disparities in the last year of life, specifically in high-value and low-value care utilization. This study evaluated racial disparities in the utilization of high-value and low-value care in the last year of life among Medicare beneficiaries with dementia or Parkinson disease.

Methods: This was a retrospective, population-based cohort analysis using data from North and South Carolina fee-for-service Medicare claims between 2013 and 2017.

Exploratory Assessment of Proteomic Network Changes in Cerebrospinal Fluid of Mild Cognitive Impairment Patients: A Pilot Study.

(1) Background: Despite the existence of well-established, CSF-based biomarkers such as amyloid-β and phosphorylated-tau, the pathways involved in the pathophysiology of Alzheimer's disease (AD) remain an active area of research. (2) Methods: We measured 3072 proteins in CSF samples of AD-biomarker positive mild cognitive impairment (MCI) participants ( = 38) and controls ( = 48), using the Explore panel of the Olink proximity extension assay (PEA). We performed group comparisons, association studies with diagnosis, age, and APOE ε4 status, overrepresentation analysis (ORA), and gene set enrichment analysis (GSEA) to determine differentially expressed proteins and dysregulated pathways.

Identifying vulnerable brain networks associated with Alzheimer's disease risk.

The selective vulnerability of brain networks in individuals at risk for Alzheimer's disease (AD) may help differentiate pathological from normal aging at asymptomatic stages, allowing the implementation of more effective interventions. We used a sample of 72 people across the age span, enriched for the APOE4 genotype to reveal vulnerable networks associated with a composite AD risk factor including age, genotype, and sex. Sparse canonical correlation analysis (CCA) revealed a high weight associated with genotype, and subgraphs involving the cuneus, temporal, cingulate cortices, and cerebellum.

Optimizing Diffusion Imaging Protocols for Structural Connectomics in Mouse Models of Neurological Conditions.

Network approaches provide sensitive biomarkers for neurological conditions, such as Alzheimer's disease (AD). Mouse models can help advance our understanding of underlying pathologies, by dissecting vulnerable circuits. While the mouse brain contains less white matter compared to the human brain, axonal diameters compare relatively well (e.

Evaluating Skilled Prehension in Mice Using an Auto-Trainer.

We describe a method to introduce naïve mice to a novel prehension (reach-to-grasp) task. Mice are housed singly in cages with a frontal slot that permits the mouse to reach out of its cage and retrieve food pellets. Minimal food restriction is employed to encourage the mice to perform the food retrieval from the slot.

Magnetic resonance imaging of mouse brain networks plasticity following motor learning.

We do not have a full understanding of the mechanisms underlying plasticity in the human brain. Mouse models have well controlled environments and genetics, and provide tools to help dissect the mechanisms underlying the observed responses to therapies devised for humans recovering from injury of ischemic nature or trauma. We aimed to detect plasticity following learning of a unilateral reaching movement, and relied on MRI performed with a rapid structural protocol suitable for in vivo brain imaging, and a longer diffusion tensor imaging (DTI) protocol executed ex vivo.

Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children.

Background: Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain.

Methods: A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence.

Long-term cortisol measures predict Alzheimer disease risk.

Objective: To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk.

Method: We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. Participants were from the Baltimore Longitudinal Study of Aging (BLSA) and submitted multiple 24-hour urine samples over an average interval of 10.

Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children.

Background: Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain.

Methods: A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence.

Hypothetical Preclinical Alzheimer Disease Groups and Longitudinal Cognitive Change.

Importance: Clinical trials testing treatments for Alzheimer disease (AD) are increasingly focused on cognitively normal individuals in the preclinical phase of the disease. To optimize observing a treatment effect, such trials need to enroll cognitively normal individuals likely to show cognitive decline over the duration of the trial.

Objective: To identify which group of cognitively normal individuals shows the greatest cognitive decline over time based on their cerebrospinal fluid biomarker profile.

Fluoxetine Maintains a State of Heightened Responsiveness to Motor Training Early After Stroke in a Mouse Model.

Background And Purpose: Data from both humans and animal models suggest that most recovery from motor impairment after stroke occurs in a sensitive period that lasts only weeks and is mediated, in part, by an increased responsiveness to training. Here, we used a mouse model of focal cortical stroke to test 2 hypotheses. First, we investigated whether responsiveness to training decreases over time after stroke.

Changes in Aβ biomarkers and associations with APOE genotype in 2 longitudinal cohorts.

Apolipoprotein E (APOE) genotype influences onset age of Alzheimer's disease but effects on disease progression are less clear. We investigated amyloid-β (Aβ) levels and change in relationship to APOE genotype, using 2 different measures of Aβ in 2 different longitudinal cohorts. Aβ accumulation was measured using positron emission tomography (PET) imaging and (11)C-Pittsburgh compound-B (PiB) in 113 Baltimore Longitudinal Study of Aging participants (mean age 77.

Changes in brain function occur years before the onset of cognitive impairment.

To develop targeted intervention strategies for the treatment of Alzheimer's disease, we first need to identify early markers of brain changes that occur before the onset of cognitive impairment. Here, we examine changes in resting-state brain function in humans from the Baltimore Longitudinal Study of Aging. We compared longitudinal changes in regional cerebral blood flow (rCBF), assessed by (15)O-water PET, over a mean 7 year period between participants who eventually developed cognitive impairment (n = 22) and those who remained cognitively normal (n = 99).

Cost-effectiveness comparison of Genechip and conventional drug susceptibility test for detecting multidrug-resistant tuberculosis in China.

Background: Genechip (CapitalBio, Beijing, China) is a system for diagnosing resistance to rifampin and isoniazid, which shows high efficiency in detecting drug-resistant tuberculosis. Here, we firstly evaluated the costs of Genechip for detecting the drug susceptibility of Mycobacterium tuberculosis, compared to conventional drug susceptibility test (DST) in laboratories in China.

Methodology/principal Findings: Data on the costs of the two tests were collected at four hospitals.

Glucose intolerance, insulin resistance, and pathological features of Alzheimer disease in the Baltimore Longitudinal Study of Aging.

Importance: Peripheral glucose homeostasis has been implicated in the pathogenesis of Alzheimer disease (AD). The relationship among diabetes mellitus, insulin, and AD is an important area of investigation. However, whether cognitive impairment seen in those with diabetes is mediated by excess pathological features of AD or other related abnormalities, such as vascular disease, remains unclear.

Personality and risk of Alzheimer's disease: new data and meta-analysis.

Background: We examine whether broad factors and specific facets of personality are associated with increased risk of incident Alzheimer's disease (AD) in a long-run longitudinal study and a meta-analysis of published studies.

Methods: Participants (n = 1671) were monitored for up to 22 years from a baseline personality assessment. The meta-analysis pooled results from up to five prospective studies (n = 5054).

The changing landscape of diagnostic services for tuberculosis.

During the last decade there has been a dramatic change in the laboratory approach to tuberculosis (TB) diagnosis in the developing world. This change began with the realization that acid-fast bacillus smear microscopy alone was totally inadequate to deal with the dual problems of human immunodeficiency virus (HIV)-associated TB and drug-resistant TB that threaten to undermine global progress in TB control. Subsequently, increased financial resources for TB laboratory services and the establishment of a systematic process for endorsement of new TB diagnostic tools and approaches by the World Health Organization (WHO) have led to rapid expansion of TB laboratory services and the availability of several new diagnostic tests that have been introduced.

Medial premotor cortex shows a reduction in inhibitory markers and mediates recovery in a mouse model of focal stroke.

Background And Purpose: Motor recovery after ischemic stroke in primary motor cortex is thought to occur in part through training-enhanced reorganization in undamaged premotor areas, enabled by reductions in cortical inhibition. Here we used a mouse model of focal cortical stroke and a double-lesion approach to test the idea that a medial premotor area (medial agranular cortex [AGm]) reorganizes to mediate recovery of prehension, and that this reorganization is associated with a reduction in inhibitory interneuron markers.

Methods: C57Bl/6 mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent photocoagulation-induced stroke in the caudal forelimb area.

Carotid atherosclerosis and prospective risk of dementia.

Background And Purpose: Although vascular risk factors have been implicated in the development of all-cause dementia and Alzheimer disease (AD), few studies have examined the association between subclinical atherosclerosis and prospective risk of dementia.

Methods: Participants from the Baltimore Longitudinal Study of Aging (n=364; age, 60-95 years; median age, 73; 60% male; 82% white) underwent initial carotid atherosclerosis assessment and subsequently were assessed for dementia and AD annually for up to 14 years (median, 7.0).

Cerebral white matter disease is associated with Alzheimer pathology in a prospective cohort.

Background: Although magnetic resonance imaging (MRI)-detected white matter disease has been correlated with cognitive decline in the elderly individuals, it is unclear whether white matter disease is primarily responsible for the cognitive deterioration or whether another process is common to both white matter disease and dementia.

Methods: We examined the relationship between Alzheimer-type brain pathology at autopsy and MRI-detected cerebral white matter disease in 50 participants from the Baltimore Longitudinal Study of Aging Autopsy Program, a prospective study of aging that includes detailed cognitive assessments.

Results: White matter disease was quantitated in pre- and postmortem MRI scans using the Cardiovascular Health Study (CHS) criteria in a blinded manner.

Personality and resilience to Alzheimer's disease neuropathology: a prospective autopsy study.

Alzheimer's disease (AD) neuropathology is found at autopsy in approximately 30% of cognitively normal older individuals. We examined whether personality traits are associated with such resilience to clinical dementia in individuals with AD neuropathology. Broad factors and specific facets of personality were assessed up to 28 years (mean 11 ± 7 years) before onset of dementia and up to 30 years (mean 15 ± 7 years) before death in a cohort (n = 111) evaluated for AD neuropathology at autopsy.

Con: Alzheimer's disease and circadian dysfunction: chicken or egg?

The development of late-onset Alzheimer's disease is believed to be influenced by genetic, socioeconomic, and lifestyle factors. Recently, converging research in animal and human studies has found that beta-amyloid (Aβ) levels in cerebrospinal fluid are modulated by sleep-wake cycles. This raises the possibility that chronic sleep loss causes brain amyloid accumulation over time and leads to the development of Alzheimer's disease.

Correspondence between in vivo (11)C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques.

The definitive Alzheimer's disease (AD) diagnosis requires postmortem confirmation of neuropathological hallmarks-amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). The advent of radiotracers for amyloid imaging presents an opportunity to investigate amyloid deposition in vivo. The (11)C-Pittsburgh compound-B (PiB)-PET ligand remains the most widely studied to date; however, regional variations in (11)C-PiB binding and the extent of agreement with neuropathological assessment have not been thoroughly investigated.

Longitudinal brain activity changes in asymptomatic Alzheimer disease.

Asymptomatic Alzheimer disease (ASYMAD) is characterized by normal cognition despite substantial AD pathology. To identify factors contributing to cognitive resilience, we compared early changes in regional cerebral blood flow (rCBF) in individuals subsequently diagnosed as ASYMAD with changes in cognitively impaired (CI) and normal older participants from the Baltimore Longitudinal Study of Aging. Participants underwent annual positron emission tomography (PET) rCBF measurements beginning 10.