Alzheimer Disease Cerebrospinal Fluid Biomarkers in a Tertiary Neurology Practice.

Objective: To evaluate the performance of Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers in a tertiary neurology clinic setting with high frequency of non-AD cases, including normal pressure hydrocephalus (NPH).

Methods: There were 534 patients who underwent AD CSF biomarkers (Roche Elecsys Aβ42, p-Tau181, total-Tau) from April 1, 2020, through April 23, 2021. A behavioral neurologist blinded to CSF results assigned a clinical diagnosis retrospectively on the basis of consensus criteria, and a neuroradiologist blinded to the diagnosis and CSF studies graded brain magnetic resonance images for indicators of CSF dynamics disorders.

Parkinson's Disease Associated with G2019S LRRK2 Mutations without Lewy Body Pathology.

Background: The G2019S leucine-rich repeat kinase 2 (LRRK2) gene mutation is an important and commonly found genetic determinant of Parkinson's disease (PD). The neuropathological findings associated with this mutation have thus far been varied but are most often associated with Lewy body (LB) pathology.

Objective: Describe a case of clinical Parkinson's disease with levodopa responsiveness found to have LRRK2 mutations and the absence of Lewy bodies.

Cerebral white matter rarefaction has both neurodegenerative and vascular causes and may primarily be a distal axonopathy.

Cerebral white matter rarefaction (CWMR) was considered by Binswanger and Alzheimer to be due to cerebral arteriolosclerosis. Renewed attention came with CT and MR brain imaging, and neuropathological studies finding a high rate of CWMR in Alzheimer disease (AD). The relative contributions of cerebrovascular disease and AD to CWMR are still uncertain.

Cognition Before and After COVID-19 Disease in Older Adults: An Exploratory Study.

Background: Older age is a major risk factor for severe COVID-19 disease which has been associated with a variety of neurologic complications, both acutely and chronically.

Objective: We sought to determine whether milder COVID-19 disease in older vulnerable individuals is also associated with cognitive and behavioral sequelae.

Methods: Neuropsychological, behavioral, and clinical outcomes before and after contracting COVID-19 disease, were compared in members of two ongoing longitudinal studies, the Arizona APOE Cohort and the national Alzheimer's Disease Research Center (ADRC).

SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19.

Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%).

Altered metabolism of mothers of young children with Autism Spectrum Disorder: a case control study.

Background: Previous research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism.

Methods: Metabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed.

Neuropsychological decline up to 20 years before incident mild cognitive impairment.

Introduction: Some Alzheimer's disease biomarker studies found amyloid changes 20 years or more in advance of expected symptoms, while cognitive changes lagged for more than a decade, but this apparent lag might reflect the sensitivities of the biomarker and cognitive assays used. How far in advance of incident amnestic mild cognitive impairment (MCI) does cognition begin to decline?

Methods: Longitudinal neuropsychological study of an apolipoprotein E e4 enriched cohort of cognitively normal individuals at entry. Linear mixed models for MCI converters (n = 65) and nonconverters (n = 719) fitted for each neuropsychological measure; annual changes compared between groups before and after linear model intersections (inflection points).

Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD.

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole-genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.

Neuropsychological comparison of incident MCI and prevalent MCI.

Introduction: Little empirical work has been done to examine differences between mild cognitive impairment (MCI) diagnosed in research settings with longitudinal data (incident MCI) and MCI diagnosed in clinical settings (prevalent MCI). Because Alzheimer's disease progresses over a clinicopathological continuum, we examined the cognitive differences between these two different sources of MCI patients.

Methods: We compared 52 consecutively identified patients with prevalent amnestic MCI with 53 incident amnestic MCI participants from the Arizona APOE study.

Subjective Cognitive Impairment and the Broad Autism Phenotype.

Introduction: Roughly 4% to 23% of the population embody stress prone personality and other traits characterizing a subclinical "broad autism phenotype" (BAP). Subjective cognitive impairment (SCI) among healthy elderly is associated with psychological distress leading us to predict BAP would be associated with SCI.

Methods: The Autism Spectrum Quotient, a self-administered 50 item questionnaire, was completed by 419 consecutive members of the Arizona APOE Cohort who underwent neuropsychological testing every 2 years.

Personality Changes During the Transition from Cognitive Health to Mild Cognitive Impairment.

Background/objectives: Behavioral problems in individuals with Alzheimer's disease (AD) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment (MCI).

Impact of Personality on Cognitive Aging: A Prospective Cohort Study.

Objectives: The aim of this study was to assess the association between personality factors and age-related longitudinal cognitive performance, and explore interactions of stress-proneness with apolipoprotein E (APOE) ɛ4, a prevalent risk factor for Alzheimer's disease (AD).

Methods: A total of 510 neuropsychiatrically healthy residents of Maricopa County recruited through media ads (mean age 57.6±10.

Gender Differences in Alzheimer Disease: Brain Atrophy, Histopathology Burden, and Cognition.

Multiple studies suggest that females are affected by Alzheimer disease (AD) more severely and more frequently than males. Other studies have failed to confirm this and the issue remains controversial. Difficulties include differences in study methods and male versus female life expectancy.

A Cross-Sectional Analysis of Late-Life Cardiovascular Factors and Their Relation to Clinically Defined Neurodegenerative Diseases.

Studies have demonstrated associations between cardiovascular factors and Alzheimer disease (AD) with minimal focus on other neurodegenerative diseases. Utilizing cross-sectional data from 17,532 individuals in the National Alzheimer's Coordinating Center, Uniform Data Set, we compared the presence of cardiovascular factors [body mass index (BMI), atrial fibrillation, hypertension, hyperlipidemia, and diabetes] in individuals carrying a diagnosis of Probable AD (ProbAD), Possible AD, vascular dementia, dementia with Lewy bodies (DLB), frontotemporal dementia, Parkinson disease, progressive supranuclear palsy, or corticobasal degeneration, with that of normals. Generalized linear mixed models were fitted with age at visit, gender, and cardiovascular factors as fixed effects and Alzheimer's Disease Centers as random effects.

APOE ε4 Genotype and the Risk for Subjective Cognitive Impairment in Elderly Persons.

The authors compared the risk for subjective cognitive impairment (SCI) between carriers of the apolipoprotein E ε4 (APOE ε4) allele (cases) and APOE ε4 noncarriers (controls). SCI was assessed by a validated self-reported questionnaire. The authors used multivariable logistic regression analyses to compute odds ratios and 95% confidence intervals adjusted for age, sex, education, and marital status.

Physical activity level and future risk of mild cognitive impairment or dementia: a critically appraised topic.

Background: The relationships between physical activity, cognition, and development of neurodegenerative diseases represent an area of intense research interest. Meta-analyses and prospective cohort studies show that greater levels of physical activity are associated with lower dementia risk. Most studies, however, depend on self-report data that are subject to recall and other biases.

Sex-based memory advantages and cognitive aging: a challenge to the cognitive reserve construct?

Education and related proxies for cognitive reserve (CR) are confounded by associations with environmental factors that correlate with cerebrovascular disease possibly explaining discrepancies between studies examining their relationships to cognitive aging and dementia. In contrast, sex-related memory differences may be a better proxy. Since they arise developmentally, they are less likely to reflect environmental confounds.

Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program.

The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains.

The neuropsychology of normal aging and preclinical Alzheimer's disease.

Objective: A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD.

Methods: Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups.

Disrupted daytime activity and altered sleep-wake patterns may predict transition to mild cognitive impairment or dementia: a critically appraised topic.

Background: There is a well-known relationship between neurodegenerative disease, disrupted sleep, and cognition. Pathologic and imaging studies have shown that regions in the brain shown to regulate sleep and circadian rhythm are abnormal in Alzheimer disease. Most of these studies have been cross-sectional, and often look at patients already with dementia.

Is donepezil effective for multiple sclerosis-related cognitive dysfunction? A critically appraised topic.

Background: Cognitive dysfunction affects approximately half of the patients with multiple sclerosis (MS). Cholinesterase inhibitor drugs are approved to treat cognitive dysfunction associated with degenerative dementia.

Objective: To critically assess current evidence regarding the efficacy of the cholinesterase inhibitor, donepezil in the treatment of MS-associated cognitive impairment.