The Bio-Hermes Study: Biomarker database developed to investigate blood-based and digital biomarkers in community-based, diverse populations clinically screened for Alzheimer's disease.

Introduction: Alzheimer's disease (AD) trial participants are often screened for eligibility by brain amyloid positron emission tomography/cerebrospinal fluid (PET/CSF), which is inefficient as many are not amyloid positive. Use of blood-based biomarkers may reduce screen failures.

Methods: We recruited 755 non-Hispanic White, 115 Hispanic, 112 non-Hispanic Black, and 19 other minority participants across groups of cognitively normal (n = 417), mild cognitive impairment (n = 312), or mild AD (n = 272) participants.

Recruitment methods and yield rates for a multisite clinical trial exploring risk reduction for Alzheimer's disease (rrAD).

Introduction: The risk reduction for Alzheimer's disease (rrAD) trial was a multisite clinical trial to assess exercise and intensive vascular pharmacological treatment on cognitive function in community-dwelling older adults at increased risk for Alzheimer's disease.

Methods: Eligibility, consent, and randomization rates across different referral sources were compared. Informal interviews conducted with each site's project team were conducted upon study completion.

Erratum.

[This corrects the article DOI: 10.1002/dad2.12334.

Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults.

Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity.

Alzheimer's disease diagnosis and management: Perspectives from around the world.

Alzheimer's disease (AD) and other dementias are a global challenge. Early diagnosis is important to manage the disease. However, there are barriers to diagnosis that differ by region.

Meaningful benefits: a framework to assess disease-modifying therapies in preclinical and early Alzheimer's disease.

Background: The need for preventive therapies that interrupt the progression of Alzheimer's disease (AD) before the onset of symptoms or when symptoms are emerging is urgent and has spurred the ongoing development of disease-modifying therapies (DMTs) in preclinical and early AD (mild cognitive impairment [MCI] to mild dementia). Assessing the meaningfulness of what are likely small initial treatment effects in these earlier stages of the AD patho-clinical disease continuum is a major challenge and warrants further consideration. BODY: To accommodate a shift towards earlier intervention in AD, we propose meaningful benefits as a new umbrella concept that encapsulates the spectrum of potentially desirable outcomes that may be demonstrated in clinical trials and other studies across the AD continuum, with an emphasis on preclinical AD and early AD (i.

Best Practices in the Clinical Management of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Consensus Statement of the CurePSP Centers of Care.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes.

Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration.

Objective: We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease progression.

Methods: Baseline plasma NfL concentrations were measured with single-molecule array in original (n = 277) and validation (n = 297) cohorts. , , and mutation carriers and noncarriers from the same families were classified by disease severity (asymptomatic, prodromal, and full phenotype) using the CDR Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR+NACC-FTLD).

Baseline Prevalence of Polypharmacy in Older Hypertensive Study Subjects with Elevated Dementia Risk: Findings from the Risk Reduction for Alzheimer's Disease Study (rrAD).

Background: Little is known about the prevalence of polypharmacy, the taking of five or more medications a day, in older adults with specific dementia risk factors.

Objective: To examine the prevalence of polypharmacy in participants at baseline in a vascular risk reduction focused Alzheimer's disease (rrAD) trial targeting older patients with hypertension and elevated dementia risk.

Methods: We conducted a detailed review of medications in a cross-sectional study of community-dwelling older adults with hypertension and elevated dementia risk.

Revised Self-Monitoring Scale: A potential endpoint for frontotemporal dementia clinical trials.

Objective: To investigate whether the Revised Self-Monitoring Scale (RSMS), an informant measure of socioemotional sensitivity, is a potential clinical endpoint for treatment trials for patients with behavioral variant frontotemporal dementia (bvFTD).

Methods: We investigated whether RSMS informant ratings reflected disease severity in 475 participants (71 bvFTD mutation+, 154 bvFTD mutation-, 12 behavioral mild cognitive impairment [MCI] mutation+, 98 asymptomatic mutation+, 140 asymptomatic mutation-). In a subset of 62 patients (20 bvFTD mutation+, 35 bvFTD mutation-, 7 MCI mutation+) who had at least 2 time points of T1-weighted images available on the same 3T scanner, we examined longitudinal changes in RSMS score over time and its correspondence to progressive gray matter atrophy.

Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint.

Introduction: Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD) is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression.

Utility of the global CDR plus NACC FTLD rating and development of scoring rules: Data from the ARTFL/LEFFTDS Consortium.

Introduction: We created global rating scoring rules for the CDR plus NACC FTLD to detect and track early frontotemporal lobar degeneration (FTLD) and to conduct clinical trials in FTLD.

Methods: The CDR plus NACC FTLD rating was applied to 970 sporadic and familial participants from the baseline visit of Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS). Each of the eight domains of the CDR plus NACC FTLD was equally weighed in determining the global score.

Genetic screening of a large series of North American sporadic and familial frontotemporal dementia cases.

Introduction: The Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) consortia are two closely connected studies, involving multiple North American centers that evaluate both sporadic and familial frontotemporal dementia (FTD) participants and study longitudinal changes.

Methods: We screened the major dementia-associated genes in 302 sporadic and 390 familial (symptomatic or at-risk) participants enrolled in these studies.

Results: Among the sporadic patients, 16 (5.

Nonlinear Z-score modeling for improved detection of cognitive abnormality.

Introduction: Conventional Z-scores are generated by subtracting the mean and dividing by the standard deviation. More recent methods linearly correct for age, sex, and education, so that these "adjusted" Z-scores better represent whether an individual's cognitive performance is abnormal. Extreme negative Z-scores for individuals relative to this normative distribution are considered indicative of cognitive deficiency.

Clinical and volumetric changes with increasing functional impairment in familial frontotemporal lobar degeneration.

Introduction: The Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations.

Methods: We examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non-mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia.

Results: Asymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes.

Exercise Training in Amnestic Mild Cognitive Impairment: A One-Year Randomized Controlled Trial.

Background: The current evidence is inconclusive to support the benefits of aerobic exercise training (AET) for preventing neurocognitive decline in patients with amnestic mild cognitive impairment (aMCI).

Objective: To examine the effect of a progressive, moderate-to-high intensity AET program on memory and executive function, brain volume, and cortical amyloid-β (Aβ) plaque deposition in aMCI patients.

Methods: This is a proof-of-concept trial that randomized 70 aMCI patients to 12 months of AET or stretching and toning (SAT, active control) interventions.

Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration.

Introduction: Some models of therapy for neurodegenerative diseases envision starting treatment before symptoms develop. Demonstrating that such treatments are effective requires accurate knowledge of when symptoms would have started without treatment. Familial frontotemporal lobar degeneration offers a unique opportunity to develop predictors of symptom onset.

Rationale and methods for a multicenter clinical trial assessing exercise and intensive vascular risk reduction in preventing dementia (rrAD Study).

Alzheimer's Disease (AD) is an age-related disease with modifiable risk factors such as hypertension, hypercholesterolemia, obesity, and physical inactivity influencing the onset and progression. There is however, no direct evidence that reducing these risk factors prevents or slows AD. The Risk Reduction for Alzheimer's Disease (rrAD) trial is designed to study the independent and combined effects of intensive pharmacological control of blood pressure and cholesterol and exercise training on neurocognitive function.

Cardiorespiratory Fitness and White Matter Neuronal Fiber Integrity in Mild Cognitive Impairment.

Background: Mounting evidence showed the self-reported levels of physical activity are positively associated with white matter (WM) integrity and cognitive performance in normal adults and patients with mild cognitive impairment (MCI). However, the objective measure of cardiorespiratory fitness (CRF) was not used in these studies.

Objective: To determine the associations of CRF measured by maximal oxygen uptake (VO2max) with WM fiber integrity and neurocognitive performance in older adults with MCI.

Ambulatory pulse pressure, brain neuronal fiber integrity, and cerebral blood flow in older adults.

Ambulatory blood pressure (ABP) reflects the end-organ vascular stress in daily life; however, its influence on brain neuronal fiber integrity and cerebral blood flow (CBF) remains unclear. The objective of this study was to determine the associations among ABP, white matter (WM) neuronal fiber integrity, and CBF in older adults. We tested 144 participants via ABP monitoring and diffusion tensor imaging.

Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy.

Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau.

Amyloid burden and sleep blood pressure in amnestic mild cognitive impairment.

Objective: To determine whether cortical β-amyloid (Aβ) deposition is associated with circadian blood pressure (BP) profiles and dynamic cerebral blood flow (CBF) regulation in patients with amnestic mild cognitive impairment (aMCI).

Methods: Forty participants with aMCI were included in this study. Cortical Aβ depositions were measured by (18)F-florbetapir PET and expressed as the standardized uptake value ratio (SUVR) relative to the cerebellum.

Central artery stiffness, baroreflex sensitivity, and brain white matter neuronal fiber integrity in older adults.

Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults.

The LIFE Cognition Study: design and baseline characteristics.

Observational studies have shown beneficial relationships between exercise and cognitive function. Some clinical trials have also demonstrated improvements in cognitive function in response to moderate-high intensity aerobic exercise; however, these have been limited by relatively small sample sizes and short durations. The Lifestyle Interventions and Independence for Elders (LIFE) Study is the largest and longest randomized controlled clinical trial of physical activity with cognitive outcomes, in older sedentary adults at increased risk for incident mobility disability.