Introduction
Blood‐based Alzheimer's disease (AD) biomarkers provide opportunities for community studies and across ethnic groups. We investigated blood biomarker concentrations in the Washington ...Heights‐Inwood Columbia Aging Project (WHICAP), a multi‐ethnic community study of aging and dementia.
Methods
We measured plasma amyloid beta (Aβ)40, Aβ42, total tau (t‐tau), phosphorylated tau (p‐tau)181, and p‐tau217, and neurofilament light chain (NfL) in 113 autopsied participants (29% with high AD neuropathological changes) and in 300 clinically evaluated individuals (42% with clinical AD). Receiver operating characteristics were used to evaluate each biomarker. We also investigated biomarkers as predictors of incident clinical AD.
Results
P‐tau181, p‐tau217, and NfL concentrations were elevated in pathologically and clinically diagnosed AD. Decreased Aβ42/Aβ40 ratio and increased p‐tau217 and p‐tau181 were associated with subsequent AD diagnosis.
Discussion
Blood‐based AD biomarker concentrations are associated with pathological and clinical diagnoses and can predict future development of clinical AD, providing evidence that they can be incorporated into multi‐ethnic, community‐based studies.
Over 900 travel-associated Zika virus cases have been identified in New York City (NYC), New York. A survey was administered in NYC adapted from the Knowledge, Attitudes, and Practices (KAP) survey ...on Zika virus developed by the World Health Organization (WHO).
A standardized, self-administered, anonymous questionnaire was administered to a convenience sample in Manhattan and the Bronx from June 30th, 2016 to October 21st, 2016. Responses were grouped into six domains based on the content and structure of the questions and were summarized using descriptive statistics or converted into a continuous knowledge score and assessed for associations with pregnancy status and travel history using linear regression.
There were 224 respondents with a mean age of 33 (SD ± 11.6) with 77% (170/224) female and 24% (51/224) pregnant. The majority (98% (213/217)) were unable to identify all of the symptoms associated with acute Zika virus infection and all modes of transmission (97% (213/219)). Most participants (85% (187/219)) identified mosquitoes as a mode of transmission. 95% (116/122) reported an association between Zika virus and microcephaly. The most concerning aspect of Zika virus in 46% (91/200) was the risk of disabilities to babies, and risk of sexual transmission (25% (49/200)). When asked what precautions pregnant persons should to reduce the risk of transmission when traveling to a Zika endemic region, only 27% (50/185) identified using condoms during intercourse or refraining from intercourse while pregnant. Knowledge of Zika transmission is significantly positively associated with pregnancy status, but not with travel history.
Our results indicate an overall poor understanding of Zika virus symptoms and possible complications, transmission modes, and current recommended prevention guidelines. Pregnancy is positively associated with Knowledge of Zika Transmission, but not other knowledge scores. Reported travel history to Zika endemic regions is not significantly associated with Zika knowledge. There is a need for implementing future public health interventions that particularly focus on protection against Zika transmission, that Zika is sexually transmitted, and risks that the Guillain-Barré Syndrome poses a risk to adults.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Queries for the presence of cardiovascular and cerebrovascular risk factors are typically assessed through self-report. However, the reliability and validity of self-reported cardiovascular and ...cerebrovascular risk factors remain inconsistent in aging research.
To determine the reliability and validity of the most frequently self-reported vascular risk factors: hypertension, diabetes, and heart disease.
1,870 individuals aged 65 years or older among African Americans, Caribbean Hispanics, and white non-Hispanic individuals were recruited as part of a community study of aging and dementia. We assessed the reliability, validity, sensitivity, specificity, and percent agreement of self-reported hypertension, diabetes, and heart disease, in comparison with direct measures of blood pressure, hemoglobin A1c (HbA1c), and medication use. The analyses were subsequently stratified by age, sex, education, and ethnic group.
Reliability of self-reported hypertension, diabetes, and heart disease was excellent. Agreement between self-reports and clinical measures was moderate for hypertension (kappa: 0.58), good for diabetes (kappa: 0.76-0.79), and moderate for heart disease (kappa: 0.45) differing slightly by age, sex, education, and ethnic group. Sensitivity and specificity for hypertension was 88.6% -78.1%, for diabetes was 87.7% -92.0% (HbA1c ≥6.5%) or 92.7% -92.8% (HbA1c ≥7%), and for heart disease was 85.8% -75.5%. Percent agreement of self-reported was 87.0% for hypertension, 91.6% -92.6% for diabetes, and 77.4% for heart disease.
Ascertainment of self-reported histories of hypertension, diabetes, and heart disease are reliable and valid compared to direct measurements or medication use.
Objective
Polygenic risk scores (PRSs) assess the individual genetic propensity to a condition by combining sparse information scattered across genetic loci, often displaying small effect sizes. Most ...PRSs are constructed in European‐ancestry populations, limiting their use in other ethnicities. Here we constructed and validated a PRS for late‐onset Alzheimer's Disease (LOAD) in Caribbean Hispanics (CH).
Methods
We used a CH discovery (n = 4,312) and independent validation sample (n = 1,850) to construct an ancestry‐specific PRS (“CH‐PRS”) and evaluated its performance alone and with other predictors using the area under curve (AUC) and logistic regression (strength of association with LOAD and statistical significance). We tested if CH‐PRS predicted conversion to LOAD in a subsample with longitudinal data (n = 1,239). We also tested the CH‐PRS in an independent replication CH cohort (n = 200) and brain autopsy cohort (n = 33). Finally, we tested the effect of ancestry on PRS by using European and African American discovery cohorts to construct alternative PRSs (“EUR‐PRS”, “AA‐PRS”).
Results
The full model (LOAD ~ CH‐PRS + sex + age + APOE‐ɛ4), achieved an AUC = 74% (ORCH‐PRS = 1.51 95%CI = 1.36–1.68), raising to >75% in APOE‐ɛ4 non‐carriers. CH‐PRS alone achieved an AUC = 72% in the autopsy cohort, raising to AUC = 83% in full model. Higher CH‐PRS was significantly associated with clinical LOAD in the replication CH cohort (OR = 1.61, 95%CI = 1.19–2.17) and significantly predicted conversion to LOAD (HR = 1.93, CI = 1.70–2.20) in the longitudinal subsample. EUR‐PRS and AA‐PRS reached lower prediction accuracy (AUC = 58% and 53%, respectively).
Interpretation
Enriching diversity in genetic studies is critical to provide an effective PRS in profiling LOAD risk across populations. ANN NEUROL 2021;90:366–376
Alzheimer’s disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age and later and is frequently accompanied by cerebrovascular pathology at ...death. An interaction between CVRFs and genetic variants might explain the pathogenesis. Genome-wide, gene by CVRF interaction analyses for AD, in 6568 patients and 8101 controls identified
FMNL2
(
p
= 6.6 × 10
–7
). A significant increase in
FMNL2
expression was observed in the brains of patients with brain infarcts and AD pathology and was associated with amyloid and phosphorylated tau deposition. FMNL2 was also prominent in astroglia in AD among those with cerebrovascular pathology. Amyloid toxicity in zebrafish increased
fmnl2a
expression in astroglia with detachment of astroglial end feet from blood vessels. Knockdown of
fmnl2a
prevented gliovascular remodeling, reduced microglial activity and enhanced amyloidosis. APP/PS1dE9 AD mice also displayed increased
Fmnl2
expression and reduced the gliovascular contacts independent of the gliotic response. Based on this work, we propose that FMNL2 regulates pathology-dependent plasticity of the blood–brain-barrier by controlling gliovascular interactions and stimulating the clearance of extracellular aggregates. Therefore, in AD cerebrovascular risk factors promote cerebrovascular pathology which in turn, interacts with
FMNL2
altering the normal astroglial-vascular mechanisms underlying the clearance of amyloid and tau increasing their deposition in brain.
BACKGROUND
Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in ...predicting cognitive impairment and AD needs examination.
METHODS
In 628 CU individuals from a multi‐ethnic cohort, amyloid beta (Aβ)42, Aβ40, phosphorylated tau‐181 (p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured in plasma.
RESULTS
Higher baseline levels of p‐tau181/Aβ42 ratio were associated with an increased risk of incident dementia. A biomarker pattern (with elevated Aβ42/Aβ40 but low p‐tau181/Aβ42) was associated with decreased dementia risk. Compared to CU, participants who developed MCI or dementia had a rapid decrease in this protective biomarker pattern reflecting AD‐specific pathological change.
DISCUSSION
Elevated levels of AD biomarker p‐tau181/Aβ42, by itself or combined with a low Aβ42/Aβ40 level, predicts clinically diagnosed AD. Individuals with a rapid change in these biomarkers may need close monitoring for the potential downward trajectory of cognition.
Highlights
We discuss a multi‐ethnic, urban community study of elderly individuals.
The study consisted of a longitudinal assessment over 6 years with repeated clinical assessments.
The study used blood‐based biomarkers as predictors of mild cognitive impairment and Alzheimer's disease.
Blood‐based phosphorylated tau (Ptau) 181 and 217 biomarkers are sensitive and specific for Alzheimer's disease. In this racial/ethnically diverse cohort study, participants were classified as ...biomarker positive (Ptau+) or negative (Ptau‐) based on Ptau 181 and 217 concentrations and as cognitively impaired (Sym) or unimpaired (Asym). The four groups, Ptau‐/Asym, Ptau+/Asym, Ptau‐/Sym, and Ptau+/Sym, differed by age, APOE‐4 allele frequency, total tau, neurofilament light chain, and cortical thickness measured by MRI. Our results add to increasing evidence that plasma Ptau 181 and 217 concentrations are valid Alzheimer's disease biomarkers in diverse populations.
Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions who experience barriers to access to care or a high burden of ...illness.
The authors conducted a randomized, controlled trial comparing telemedicine case management to usual care, with blinding of those obtaining outcome data, in 1,665 Medicare recipients with diabetes, aged 55 years or greater, and living in federally designated medically underserved areas of New York State. The primary endpoints were HgbA1c, blood pressure, and low-density lipoprotein (LDL) cholesterol levels.
In the intervention group (n = 844), mean HgbA1c improved over one year from 7.35% to 6.97% and from 8.35% to 7.42% in the subgroup with baseline HgbA1c ≥7% (n = 353). In the usual care group (n = 821) mean HgbA1c improved over one year from 7.42% to 7.17%. Adjusted net reductions (one-year minus baseline mean values in each group, compared between groups) favoring the intervention were as follows: HgbA1c, 0.18% (p = 0.006), systolic and diastolic blood pressure, 3.4 (p = 0.001) and 1.9 mm Hg (p < 0.001), and LDL cholesterol, 9.5 mg/dL (p < 0.001). In the subgroup with baseline HgbA1c ≥7%, net adjusted reduction in HgbA1c favoring the intervention group was 0.32% (p = 0.002). Mean LDL cholesterol level in the intervention group at one year was 95.7 mg/dL. The intervention effects were similar in magnitude in the subgroups living in New York City and upstate New York.
Telemedicine case management improved glycemic control, blood pressure levels, and total and LDL cholesterol levels at one year of follow-up.
Background
Recent studies have evaluated Alzheimer’s disease (AD) associated with cerebrovascular and cardiovascular risk factors. Stroke history mediates association between late‐onset AD and ...cardiovascular disease risk factors (Tosto et al., 2016). Our research investigated stroke as a potential moderator between polygenic risk score (PRS) and Alzheimer’s disease.
Method
Participants were enrolled in the multi‐ethnic Washington Heights‐Inwood Columbia Aging Project (WHICAP). 653 non‐Hispanic white and 2285 Caribbean Hispanic participants were included based on GWAS data and stroke status (self‐reported history of stroke or MRI‐visualized stroke). A concordance analysis assessed stroke group agreement. PRS from GWAS statistics was calculated for both populations. Following calculation of moderators by stroke status on population‐specific PRS, binomial logistic regression models were conducted. Model outcome was Alzheimer’s disease, which incorporated four diagnoses: Pure Alzheimer’s disease, Probable Alzheimer’s disease with Stroke, Alzheimer’s disease with Parkinsonism, and Atypical Alzheimer’s disease. Another set of models was conducted for the Caribbean Hispanic population towards a general outcome of Alzheimer’s disease alone.
Result
Concordance analyses among all 4987 WHICAP participants showed Cohen’s kappa of ‐0.033 and p of 0.001* (p* < 0.05), indicating no concordance between self‐reported and MRI‐visualized stroke groups; this is consistent with observation by Reitz et al., 2009. Within the Caribbean Hispanic population, MRI‐visualized stroke models for Alzheimer’s disease (four types) showed moderator significance (p of 0.002*, 0.007*, and 0.001* for Models 1, 2, 3 respectively) and MRI‐visualized stroke models towards generalized Alzheimer’s disease showed moderator significance (p of 0.152, 0.041*, and 0.020* for Models 1, 2, 3 respectively).
Conclusion
Stroke is likely to be an important moderator of PRS and Alzheimer’s disease risk in MRI‐visualized stroke models, while a self‐reported history of stroke was not related.
Introduction
Progranulin (GRN) mutations occur in frontotemporal lobar degeneration (FTLD) and in Alzheimer's disease (AD), often with TDP‐43 pathology.
Methods
We determined the frequency of rs5848 ...and rare, pathogenic GRN mutations in two autopsy and one family cohort. We compared Braak stage, β‐amyloid load, hyperphosphorylated tau (PHFtau) tangle density and TDP‐43 pathology in GRN carriers and non‐carriers.
Results
Pathogenic GRN mutations were more frequent in all cohorts compared to the Genome Aggregation Database (gnomAD), but there was no evidence for association with AD. Pathogenic GRN carriers had significantly higher PHFtau tangle density adjusting for age, sex and APOE ε4 genotype. AD patients with rs5848 had higher frequencies of hippocampal sclerosis and TDP‐43 deposits. Twenty‐two rare, pathogenic GRN variants were observed in the family cohort.
Discussion
GRN mutations in clinical and neuropathological AD increase the burden of tau‐related brain pathology but show no specific association with β‐amyloid load or AD.
PDF
