A Canonical Correlation Approach Towards Identifying Latent Neurofeedback Responses in Patients with Schizophrenia.

Patients with schizophrenia exhibit frontal gamma dysregulation, and associated impairments in cognitive function. To improve self regulation of frontal gamma activity, we designed a double-blind, placebo-controlled randomized clinical trial to test a novel neurofeedback (NFB) protocol, which rewards active maintenance of current or higher levels of frontal gamma coherence (gcoh-NFB). We report here unique treatment responses among participants with high versus low baseline working memory (WM) function.

α-Synuclein Seed Amplification Assay Amplification Parameters and the Risk of Progression in Prodromal Parkinson Disease.

Objectives: Tools are needed to evaluate the risk of developing Parkinson disease (PD) in at-risk populations. In this study, we examine differences in alpha-synuclein seed amplification assay (αSyn-SAA) qualitative results and amplification parameters between nonmanifesting carriers (NMCs) of PD-related pathogenic variants, prodromal PD, and PD and the risk of developing a synucleinopathy in participants with prodromal PD.

Methods: Cross-sectional and longitudinal CSF αSyn-SAA results from participants in the Parkinson's Progression Markers Initiative were analyzed.

Enrichment for clinical trials of early AD: Combining genetic risk factors and plasma p-tau as screening instruments.

Introduction: Identifying low-cost, minimally-invasive screening instruments for Alzheimer's disease (AD) trial enrichment will improve the efficiency of AD trials.

Methods: A total of 685 cognitively normal (CN) individuals and individuals with mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were grouped according to cutoffs of genetic risk factor (G) polygenic hazard score (PHS) and tau pathology (T) plasma phosphorylated tau-181 (p-tau181) into four groups: G+T+, G-T-, G+T-, and G-T+. We assessed the associations between group level and longitudinal cognitive decline and AD conversion.

Memory-related brain potentials for visual objects in early AD show impairment and compensatory mechanisms.

Impaired episodic memory is the primary feature of early Alzheimer's disease (AD), but not all memories are equally affected. Patients with AD and amnestic Mild Cognitive Impairment (aMCI) remember pictures better than words, to a greater extent than healthy elderly. We investigated neural mechanisms for visual object recognition in 30 patients (14 AD, 16 aMCI) and 36 cognitively unimpaired healthy (19 in the "preclinical" stage of AD).

Exercise: Just What the Doctor Ordered, But Why? Elucidating Mechanisms for Women's Increased High-Density Lipoprotein Benefit From Exercise and for the Health ABC Study.

High-density lipoprotein (HDL) is protective against cardiovascular disease. Exercise can increase HDL concentration, and some evidence suggests that this effect occurs more strongly in women than in men. Both HDL and exercise are associated with inflammation.

A simple genetic stratification method for lower cost, more expedient clinical trials in early Alzheimer's disease: A preliminary study of tau PET and cognitive outcomes.

Introduction: Identifying individuals who are most likely to accumulate tau and exhibit cognitive decline is critical for Alzheimer's disease (AD) clinical trials.

Methods: Participants (N = 235) who were cognitively normal or with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative were stratified by a cutoff on the polygenic hazard score (PHS) at 65th percentile (above as high-risk group and below as low-risk group). We evaluated the associations between the PHS risk groups and tau positron emission tomography and cognitive decline, respectively.

Sex differences in Alzheimer's disease: plasma MMP-9 and markers of disease severity.

Background: Studies have reported higher plasma matrix metalloproteinase-9 (MMP-9) levels in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Despite evidence that MMP-9 activity and its influence on AD pathophysiology may be modulated by sex hormones, sex differences in the association between MMP-9 and AD biomarkers and cognition have not been explored.

Methods: Our sample included 238 amyloid-β (Aβ)-positive participants with MCI or AD dementia from the Alzheimer's Disease Neuroimaging Initiative (37.

Sex differences in plasma p-tau181 associations with Alzheimer's disease biomarkers, cognitive decline, and clinical progression.

Studies have shown that women on the Alzheimer's disease (AD) continuum have more pathological tau in the brain and cerebrospinal fluid (CSF), than men. Some studies have found that higher levels of tau biomarkers are more strongly associated with clinical AD, cognitive decline and neurodegeneration in women than in men. Despite major developments in the use of plasma tau phosphorylated at threonine 181 (p-tau181) as an AD biomarker, it is unknown whether these sex differences apply to plasma p-tau181.

TDP-43 Pathology Exacerbates Cognitive Decline in Primary Age-Related Tauopathy.

Objective: Primary age-related tauopathy (PART) refers to tau neurofibrillary tangles restricted largely to the medial temporal lobe in the absence of significant beta-amyloid plaques. PART has been associated with cognitive impairment, but contributions from concomitant limbic age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) are underappreciated.

Methods: We compare prevalence of LATE-NC and vascular copathologies in age- and Braak-matched patients with PART (n = 45, Braak stage I-IV, Thal phase 0-2) or early stage Alzheimer disease neuropathologic change (ADNC; n = 51, Braak I-IV, Thal 3-5), and examine their influence on clinical and cognitive decline.

Sex and ɛ4 modify the effect of cardiovascular risk on tau in cognitively normal older adults.

The interaction between ɛ4 and vascular risk factors on cognitive function is stronger in women than in men. These effects may be mediated by the amount of tau pathology in the brain. Therefore, we examined whether ɛ4 and sex modify cross-sectional associations between cardiovascular risk and tau deposition in cognitively normal older adults from the Alzheimer's Disease Neuroimaging Initiative.

Perceived Stress in Older Dementia Caregivers: Mediation by Loneliness and Depression.

Coupled with aging, chronic stress experienced by dementia caregivers often leads to deteriorating health. Comparing caregivers and non-caregivers, we tested whether depression and loneliness mediate the relationship between caregiver status and a measure of chronic stress, the Perceived Stress Scale. Seventy-six cognitively normal older adults (mean age 72.

A phase II study repurposing atomoxetine for neuroprotection in mild cognitive impairment.

The locus coeruleus is the initial site of Alzheimer's disease neuropathology, with hyperphosphorylated Tau appearing in early adulthood followed by neurodegeneration in dementia. Locus coeruleus dysfunction contributes to Alzheimer's pathobiology in experimental models, which can be rescued by increasing norepinephrine transmission. To test norepinephrine augmentation as a potential disease-modifying therapy, we performed a biomarker-driven phase II trial of atomoxetine, a clinically-approved norepinephrine transporter inhibitor, in subjects with mild cognitive impairment due to Alzheimer's disease.

Committee on High-quality Alzheimer's Disease Studies (CHADS) consensus report.

Background: Consensus guidance for the development and identification of high-quality Alzheimer's disease clinical trials is needed for protocol development and conduct of clinical trials.

Methods: An ad hoc consensus committee was convened in conjunction with the Alzheimer's Association to develop consensus recommendations.

Results: Consensus was readily reached for the need to provide scientific justification, registration of trials, institutional review board oversight, conflict of interest disclosure, funding source disclosure, defined trial population, recruitment resources, definition of the intervention, specification of trial duration, appropriate payment for participant engagement, risk-benefit disclosure as part of the consent process, and the requirement to disseminate and/or publish trial results even if the study is negative.

Age-at-Onset and -Related Heterogeneity in Pathologically Confirmed Sporadic Alzheimer Disease.

Objective: To characterize age-related clinical heterogeneity in Alzheimer disease (AD) and determine whether it is modified by genotype or concomitant non-AD pathology, we analyzed data from 1,750 patients with sporadic, pathologically confirmed severe AD.

Methods: In this retrospective cohort study, regression and mixed effects models assessed effects of estimated age at onset, genotype, and their interaction on standardized clinical, cognitive, and pathologic outcome measures from the National Alzheimer's Coordinating Center database.

Results: A bimodal distribution of age at onset frequency in ε4- cases showed best separation at age 63.

Differential blood DNA methylation across Lewy body dementias.

Introduction: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by cognitive alterations, visual hallucinations, and motor impairment. Diagnosis is based on type and timing of clinical manifestations; however, determination of clinical subtypes is challenging. The utility of blood DNA methylation as a biomarker for Lewy body disorders (LBD) is mostly unexplored.

Power formulas for mixed effects models with random slope and intercept comparing rate of change across groups.

We have previously derived power calculation formulas for cohort studies and clinical trials using the longitudinal mixed effects model with random slopes and intercepts to compare rate of change across groups [Ard & Edland, Power calculations for clinical trials in Alzheimer's disease. J Alzheim Dis 2011;21:369-77]. We here generalize these power formulas to accommodate 1) missing data due to study subject attrition common to longitudinal studies, 2) unequal sample size across groups, and 3) unequal variance parameters across groups.

Community memory screening as a strategy for recruiting older adults into Alzheimer's disease research.

Background: Growing awareness of Alzheimer's disease (AD) has prompted a demand for quick and effective ways to screen for memory loss and cognitive decline in large numbers of individuals in the community. Periodic Memory Screening Day events provide free, brief cognitive screening aimed at those 65 years and older, and can serve as an opportunity to gauge participants' attitudes towards AD research and recruit them into ongoing research projects.

Methods: Over 6 single-day events in 2 years, more than 574 individuals were individually screened using the MoCA and a story recall task (immediate and delayed), given feedback about their performance, and introduced to AD research and opportunities to participate.

Cognitive decline profiles differ in Parkinson disease dementia and dementia with Lewy bodies.

Objective: To examine whether domain-specific patterns of cognitive impairment and trajectories of decline differed in patients with clinically diagnosed Parkinson disease dementia (PDD) (N = 29) and autopsy-confirmed dementia with Lewy bodies (DLB) (N = 58) or Alzheimer disease (AD) (N = 174) and to determine the impact of pooling patients with PDD and DLB in clinical trials targeting cognition.

Methods: Patients were matched on demographics and level of global cognitive impairment. Patterns of cross-sectional performance and longitudinal decline were examined in 4 cognitive domains: Visuospatial, Memory, Executive, and Language.

The CAIDE Dementia Risk Score and the Honolulu-Asia Aging Study.

Introduction: The CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) dementia risk score is based on demographic, genetic, and modifiable risk factors in midlife and has been shown to be predictive of later-life dementia.

Objective: To test the predictive capacity of the CAIDE dementia risk score among a cohort of Japanese-American men.

Methods: Midlife measures were obtained from a sample of 3,582 Japanese-American men in the Honolulu Heart Program (1965-1968, average age = 53.

Brain Injury and Later-Life Cognitive Impairment and Neuropathology: The Honolulu-Asia Aging Study.

Background: Findings are inconsistent regarding the role of traumatic head injury in the subsequent development of neurologic outcomes.

Objective: Examine the relationship between head injury and later cognitive impairment.

Methods: A sample of 3,123 Japanese-American men was assessed for history of head injury and evaluated for cognitive impairment using the Cognitive Abilities Screening Instrument (CASI).