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1.
Am Heart J ; 276: 31-38, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39067559

ABSTRACT

BACKGROUND: The association of malignant left ventricular hypertrophy (LVH), a specific subphenotype of LVH characterized by elevated levels of high-sensitivity cardiac troponin (hs-cTnT) or N-terminal pro-B-type natriuretic peptide (NT-proBNP), with cognitive decline remains understudied. METHODS: This post-hoc analysis included a total of 8,027 (67.9 ± 9.3 years) SPRINT MIND trial participants who had with at least 1 follow-up cognitive assessment. Participants were classified into 6 groups on the basis of LVH status on electrocardiogram (ECG), and elevations in levels of hs-cTnT ≥14 ng/L or NT-proBNP ≥125 pg/mL at baseline visit. Multivariate Cox proportional hazard models were used to examine the association of LVH/biomarker groups with incident probable dementia, mild cognitive impairment (MCI) and a composite of MCI/probable dementia. RESULTS: Over a median follow-up period of 5 years, there were 306, 597, and 818 incidents of MCI, probable dementia and a composite of MCI/probable dementia, respectively. Compared with participants without LVH and normal biomarker levels, those with concomitant LVH and elevated levels of both biomarkers were associated with a higher risk of probable dementia (HR, 2.50; 95% CI (1.26-4.95), MCI (HR, 1.78; 95% CI (0.99-3.23) and the composite of MCI/ probable dementia (HR, 1.89; 95% CI, 1.16-3.10). CONCLUSIONS: Among SPRINT participants, malignant LVH is associated with incident probable dementia and mild cognitive impairment. These findings underscore the potential utility of measuring hs-cTnT and NT-proBNP levels when LVH is detected on ECG, aiding in the differentiation of individuals with a favorable risk for cognitive impairment from those with a higher risk.


Subject(s)
Biomarkers , Cognitive Dysfunction , Dementia , Electrocardiography , Hypertrophy, Left Ventricular , Natriuretic Peptide, Brain , Peptide Fragments , Humans , Male , Female , Hypertrophy, Left Ventricular/epidemiology , Hypertrophy, Left Ventricular/diagnosis , Hypertrophy, Left Ventricular/blood , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/blood , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Aged , Peptide Fragments/blood , Natriuretic Peptide, Brain/blood , Biomarkers/blood , Dementia/epidemiology , Dementia/blood , Dementia/diagnosis , Dementia/etiology , Middle Aged , Troponin T/blood , Follow-Up Studies , Risk Factors , Incidence , Proportional Hazards Models , Risk Assessment/methods
2.
Alzheimers Dement ; 20(8): 5271-5280, 2024 08.
Article in English | MEDLINE | ID: mdl-38984649

ABSTRACT

INTRODUCTION: Substantial racial and ethnic disparities in hypertension and dementia exist in the United States. We evaluated the effect of maintaining systolic blood pressure (SBP) below clinical thresholds on dementia incidence. METHODS: We included 6806 Multi-Ethnic Study of Atherosclerosis participants (44 to 84 years old). We implemented the parametric g-formula to simulate the hypothetical interventions to reduce SBP below 120 and 140 mmHg over time, accounting for time-varying confounding. We estimated risk ratios (RRs) and risk differences for dementia incidence at 19 years. RESULTS: The RRs (95% confidence intervals [CIs]) comparing an intervention reducing SBP below 120 mmHg to no intervention were 0.93 (0.87 to 0.99) for total sample, 0.95 (0.88 to 1.02) for White, 0.90 (0.79 to 1.02) for Black, 0.90 (0.78 to 1.05) for Latino, and 1.16 (0.83 to 1.55) for Chinese American participants. Results for lowering SBP below 140 mmHg and with death as competing event were attenuated. DISCUSSION: The reduction of SBP below 120 mmHg over time has modest effects on reducing dementia incidence. More work is needed to understand the heterogeneity across racial and ethnic groups. HIGHLIGHTS: There is a potential beneficial effect in lowering SBP to reduce the risk of dementia, which may vary by race and ethnicity. The percentage of participants who would need intervention on blood pressure to meet clinical thresholds is greater for Black and Latino communities. Results are sensitive to the way that death is specified in the research question and analysis.


Subject(s)
Atherosclerosis , Blood Pressure , Dementia , Hypertension , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antihypertensive Agents/therapeutic use , Atherosclerosis/ethnology , Atherosclerosis/prevention & control , Blood Pressure/physiology , Dementia/ethnology , Dementia/epidemiology , Dementia/prevention & control , Ethnicity , Hypertension/ethnology , Incidence , Risk Factors , United States/epidemiology , Racial Groups
3.
Alzheimers Dement ; 20(6): 4159-4173, 2024 06.
Article in English | MEDLINE | ID: mdl-38747525

ABSTRACT

INTRODUCTION: We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities. METHODS: We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aß] 42/40, phosphorylated tau 181) and neuroimaging measures of amyloid deposition (Aß-positron emission tomography [PET]), total brain volume, white matter hyperintensity volume, diffusion-weighted fractional anisotropy, and neurite orientation dispersion and density imaging free water. Participants were adjudicated as cognitively unimpaired (CU; N = 299), mild cognitive impairment (MCI; N = 192), or dementia (DEM; N = 65). Biomarkers were compared across groups stratified by diagnosis, sex, race, and APOE ε4 carrier status. General linear models examined plasma-imaging associations before and after adjusting for demographics (age, sex, race, education), APOE ε4 status, medications, diagnosis, and other factors (estimated glomerular filtration rate [eGFR], body mass index [BMI]). RESULTS: Plasma biomarkers differed across diagnostic groups (DEM > MCI > CU), were altered in Aß-PET-positive individuals, and were associated with poorer brain health and kidney function. DISCUSSION: eGFR and BMI did not substantially impact associations between plasma and neuroimaging biomarkers. HIGHLIGHTS: Plasma biomarkers differ across diagnostic groups (DEM > MCI > CU) and are altered in Aß-PET-positive individuals. Altered plasma biomarker levels are associated with poorer brain health and kidney function. Plasma and neuroimaging biomarker associations are largely independent of comorbidities.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Magnetic Resonance Imaging , Positron-Emission Tomography , Humans , Male , Female , Biomarkers/blood , Aged , Alzheimer Disease/blood , Alzheimer Disease/diagnostic imaging , Amyloid beta-Peptides/blood , Comorbidity , Brain/diagnostic imaging , Brain/pathology , Dementia/blood , Dementia/diagnostic imaging , tau Proteins/blood , Cohort Studies , Independent Living , Cognitive Dysfunction/blood , Cognitive Dysfunction/diagnostic imaging , Middle Aged , Neuroimaging
4.
Alzheimers Dement ; 20(2): 941-953, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37828734

ABSTRACT

INTRODUCTION: Retinal vascular network changes may reflect the integrity of the cerebral microcirculation, and may be associated with cognitive impairment. METHODS: Associations of retinal vascular measures with cognitive function and MRI biomarkers were examined amongst Multi-Ethnic Study of Atherosclerosis (MESA) participants in North Carolina who had gradable retinal photographs at Exams 2 (2002 to 2004, n = 313) and 5 (2010 to 2012, n = 306), and detailed cognitive testing and MRI at Exam 6 (2016 to 2018). RESULTS: After adjustment for covariates and multiple comparisons, greater arteriolar fractal dimension (FD) at Exam 2 was associated with less isotropic free water of gray matter regions (ß = -0.0005, SE = 0.0024, p = 0.01) at Exam 6, while greater arteriolar FD at Exam 5 was associated with greater gray matter cortical volume (in mm3 , ß = 5458, SE = 20.17, p = 0.04) at Exam 6. CONCLUSION: Greater arteriolar FD, reflecting greater complexity of the branching pattern of the retinal arteries, is associated with MRI biomarkers indicative of less neuroinflammation and neurodegeneration.


Subject(s)
Atherosclerosis , Fractals , Humans , Retinal Vessels/diagnostic imaging , Atherosclerosis/diagnostic imaging , Neuroimaging , Biomarkers , Cognition
5.
Diabetologia ; 66(8): 1442-1449, 2023 08.
Article in English | MEDLINE | ID: mdl-37221246

ABSTRACT

AIMS/HYPOTHESIS: The aim of this work was to evaluate whether the association of prediabetes with dementia is explained by the intervening onset of diabetes. METHODS: Among participants of the Atherosclerosis Risk in Communities (ARIC) study we defined baseline prediabetes as HbA1c 39-46 mmol/mol (5.7-6.4%) and subsequent incident diabetes as a self-reported physician diagnosis or use of diabetes medication. Incident dementia was ascertained via active surveillance and adjudicated. We quantified the association of prediabetes with dementia risk before and after accounting for the subsequent development of diabetes among ARIC participants without diabetes at baseline (1990-1992; participants aged 46-70 years). We also evaluated whether age at diabetes diagnosis modified the risk of dementia. RESULTS: Among 11,656 participants without diabetes at baseline, 2330 (20.0%) had prediabetes. Before accounting for incident diabetes, prediabetes was significantly associated with the risk of dementia (HR 1.12 [95% CI 1.01, 1.24]). After accounting for incident diabetes, the association was attenuated and non-significant (HR 1.05 [95% CI 0.94, 1.16]). Earlier age of onset of diabetes had the strongest association with dementia: HR 2.92 (95% CI 2.06, 4.14) for onset before 60 years; HR 1.73 (95% CI 1.47, 2.04) for onset at 60-69 years; and HR 1.23 (95% CI 1.08, 1.40) for onset at 70-79 years. CONCLUSIONS/INTERPRETATION: Prediabetes is associated with dementia risk but this risk is explained by the subsequent development of diabetes. Earlier age of onset of diabetes substantially increases dementia risk. Preventing or delaying progression of prediabetes to diabetes will reduce dementia burden.


Subject(s)
Atherosclerosis , Dementia , Diabetes Mellitus , Prediabetic State , Humans , Prediabetic State/complications , Prediabetic State/epidemiology , Risk Factors , Diabetes Mellitus/epidemiology , Atherosclerosis/epidemiology , Dementia/epidemiology , Dementia/complications
6.
Stroke ; 54(5): 1280-1288, 2023 05.
Article in English | MEDLINE | ID: mdl-36951053

ABSTRACT

BACKGROUND: Cardiovascular health may be used for prevention of cerebral vascular disease; however, data on the association of cardiovascular health across midlife and late-life with late-life cerebral vascular disease are lacking. Our aim was to examine whether midlife or late-life cardiovascular health as well as changes of cardiovascular health within midlife and between midlife and late-life were associated with prevalence of magnetic resonance imaging markers of cerebral vascular disease at late-life. METHODS: Prospective cohort study including 1638 participants from the Atherosclerosis Risk in Communities Study who took part in 2 visits at midlife (mean ages, 53 and 59 years), and a late-life visit (mean age, 76 years). A cardiovascular health Life's Simple 7 score (range, 0-12/0-14, depending on diet availability) including 6 out of 7 items was calculated at each visit, with weight assigned to each item as poor (0), intermediate (1), or ideal (2). Participants underwent 3T brain magnetic resonance imaging scans in late-life visit. Outcomes were white matter hyperintensity volume, microbleeds, and lacunar, subcortical, and cortical infarcts at late-life. Linear and logistic regression models were used to assess the associations of cardiovascular health in midlife and late-life, and improvement of cardiovascular health within midlife, and from midlife to late-life with magnetic resonance imaging markers of cerebral vascular disease, adjusting for potential confounders. RESULTS: A higher cardiovascular health in midlife, improvement of cardiovascular health within midlife, higher cardiovascular health at late-life, and improvement of cardiovascular health from midlife to late-life were associated with a lower prevalence of cerebral vascular disease markers. For example, improvement in cardiovascular health (per point) from midlife to late-life was associated with smaller white matter hyperintensity volume (ß, -0.07 [95% CI, -0.10 to -0.04]) and lower odds of microbleeds (odds ratio, 0.93 [0.90-0.97]), lacunar (odds ratio, 0.93 [0.89-0.97]), subcortical (odds ratio, 0.93 [0.89-0.97]), and cortical infarcts (odds ratio, 0.92 [0.87-0.97]). CONCLUSIONS: Improving cardiovascular health within midlife and from midlife to late-life may prevent development of cerebral vascular disease.


Subject(s)
Brain , Cerebrovascular Disorders , Humans , Middle Aged , Aged , Prospective Studies , Risk Factors , Brain/pathology , Magnetic Resonance Imaging , Cerebrovascular Disorders/pathology , Infarction/pathology , Cerebral Hemorrhage/pathology
7.
Ann Neurol ; 92(4): 607-619, 2022 10.
Article in English | MEDLINE | ID: mdl-35732594

ABSTRACT

OBJECTIVE: Midlife vascular risk factors (MVRFs) are associated with incident dementia, as are amyloid ß (Aß) deposition and neurodegeneration. Whether vascular and Alzheimer disease-associated factors contribute to dementia independently or interact synergistically to reduce cognition is poorly understood. METHODS: Participants in the Atherosclerosis Risk in Communities-Positron Emission Tomography study were followed from 1987-1989 (45-64 years old) through 2016-2017 (74-94 years old), with repeat cognitive assessment and dementia adjudication. In 2011-2013, dementia-free participants underwent brain magnetic resonance imaging (with white matter hyperintensity [WMH] and brain volume measurement) and florbetapir (Aß) positron emission tomography. The relative contributions of vascular risk and injury (MVRFs, WMH volume), elevated Aß standardized uptake value ratio (SUVR), and neurodegeneration (smaller temporoparietal brain regions) to incident dementia were evaluated with adjusted Cox models. RESULTS: In 298 individuals, 36 developed dementia (median follow-up = 4.9 years). Midlife hypertension and Aß each independently predicted dementia risk (hypertension: hazard ratio [HR] = 2.57, 95% confidence interval [CI] = 1.16-5.67; Aß SUVR [per standard deviation (SD)]: HR = 2.57, 95% CI = 1.72-3.84), but did not interact significantly, whereas late life diabetes (HR = 2.50, 95% CI = 1.18-5.28) and Aß independently predicted dementia risk. WMHs (per SD: HR = 1.51, 95% CI = 1.03-2.20) and Aß SUVR (HR = 2.52, 95% CI = 1.83-3.47) independently contributed to incident dementia, but WMHs lost significance when MVRFs were included. Smaller temporoparietal brain regions were associated with incident dementia, independent of Aß and MVRFs (HR = 2.18, 95% CI = 1.18-4.01). INTERPRETATION: Midlife hypertension and late life Aß are independently associated with dementia risk, without evidence for synergy on a multiplicative scale. Given the independent contributions of vascular and amyloid mechanisms, multiple pathways should be considered when evaluating interventions to reduce the burden of dementia. ANN NEUROL 2022;92:607-619.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Hypertension , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Amyloid/metabolism , Amyloid beta-Peptides/metabolism , Brain/pathology , Cognitive Dysfunction/pathology , Humans , Hypertension/epidemiology , Magnetic Resonance Imaging , Middle Aged , Positron-Emission Tomography
8.
Alzheimers Dement ; 19(7): 3119-3128, 2023 07.
Article in English | MEDLINE | ID: mdl-36724324

ABSTRACT

INTRODUCTION: Discrimination negatively impacts health and may contribute to racial/ethnic disparities in dementia risk. METHODS: Experiences of lifetime and everyday discrimination were assessed among 6509 Multi-Ethnic Study of Atherosclerosis (MESA) participants. We assessed the association of discrimination with incidence of dementia including adjustment for important risk factors, cohort attrition, and we assessed for effect modification by race/ethnicity. RESULTS: Prevalence of any lifetime discrimination in MESA was 42%, highest among Black adults (72%). Over a median 15.7 years of follow-up, there were 466 incident cases of dementia. Lifetime discrimination, but not everyday discrimination, was associated with incident dementia (Wald p = 0.03). Individuals reporting lifetime discrimination in ≥2 domains (compared to none) had greater risk for dementia (hazard ratio: 1.40; 95%: 1.08, 1.82) after adjustment for sociodemographic, clinical, and behavioral risk factors. Associations did not differ by race/ethnicity. CONCLUSIONS: These findings demonstrate an association of greater experiences of lifetime discrimination with incident dementia.


Subject(s)
Dementia , Ethnicity , Racism , Adult , Humans , Black People , Dementia/epidemiology , Dementia/ethnology , Dementia/etiology , Dementia/psychology , Risk Factors , Self Report , Racism/ethnology , Racism/psychology
9.
Alzheimers Dement ; 19(4): 1143-1151, 2023 04.
Article in English | MEDLINE | ID: mdl-35869977

ABSTRACT

INTRODUCTION: We investigated associations between neighborhood racial/ethnic segregation and cognitive change. METHODS: We used data (n = 1712) from the Multi-Ethnic Study of Atherosclerosis. Racial/ethnic segregation was assessed using Getis-Ord (Gi*) z-scores based on American Community Survey Census tract data (higher Gi* = greater spatial clustering of participant's race/ethnicity). Global cognition and processing speed were assessed twice, 6 years apart. Adjusted multilevel linear regression tested associations between Gi* z-scores and cognition. Effect modification by race/ethnicity, income, education, neighborhood socioeconomic status, and neighborhood social support was tested. RESULTS: Participants were on average 67 years old; 43% were White, 11% Chinese, 29% African American/Black, 17% Hispanic; 40% had high neighborhood segregation (Gi* > 1.96). African American/Black participants with greater neighborhood segregation had greater processing speed decline in stratified analyses, but no interactions were significant. DISCUSSION: Segregation was associated with greater processing speed declines among African American/Black participants. Additional follow-ups and comprehensive cognitive batteries may further elucidate these findings. HIGHLIGHTS: A study of neighborhood racial/ethnic segregation and change in cognition. Study was based on a racially and geographically diverse, population-based cohort of older adults. Racial/ethnic segregation (clustering) was measured by the Getis-ord (Gi*) statistic. We saw faster processing speed decline among Black individuals in segregated neighborhoods.


Subject(s)
Atherosclerosis , Ethnicity , Residential Segregation , Aged , Humans , Black or African American , Hispanic or Latino , White , Asian
10.
Alzheimers Dement ; 19(11): 4952-4966, 2023 11.
Article in English | MEDLINE | ID: mdl-37071449

ABSTRACT

INTRODUCTION: Brain cell-derived small extracellular vesicles (sEVs) in blood offer unique cellular and molecular information related to the onset and progression of Alzheimer's disease (AD). We simultaneously enriched six specific sEV subtypes from the plasma and analyzed a selected panel of microRNAs (miRNAs) in older adults with/without cognitive impairment. METHODS: Total sEVs were isolated from the plasma of participants with normal cognition (CN; n = 11), mild cognitive impairment (MCI; n = 11), MCI conversion to AD dementia (MCI-AD; n = 6), and AD dementia (n = 11). Various brain cell-derived sEVs (from neurons, astrocytes, microglia, oligodendrocytes, pericytes, and endothelial cells) were enriched and analyzed for specific miRNAs. RESULTS: miRNAs in sEV subtypes differentially expressed in MCI, MCI-AD, and AD dementia compared to the CN group clearly distinguished dementia status, with an area under the curve (AUC) > 0.90 and correlated with the temporal cortical region thickness on magnetic resonance imaging (MRI). DISCUSSION: miRNA analyses in specific sEVs could serve as a novel blood-based molecular biomarker for AD. HIGHLIGHTS: Multiple brain cell-derived small extracellular vesicles (sEVs) could be isolated simultaneously from blood. MicroRNA (miRNA) expression in sEVs could detect Alzheimer's disease (AD) with high specificity and sensitivity. miRNA expression in sEVs correlated with cortical region thickness on magnetic resonance imaging (MRI). Altered expression of miRNAs in sEVCD31 and sEVPDGFRß suggested vascular dysfunction. miRNA expression in sEVs could predict the activation state of specific brain cell types.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Extracellular Vesicles , MicroRNAs , Humans , Aged , Alzheimer Disease/pathology , Endothelial Cells/pathology , Cognitive Dysfunction/diagnosis , MicroRNAs/genetics , Biomarkers
11.
Alzheimers Dement ; 19(5): 1821-1831, 2023 05.
Article in English | MEDLINE | ID: mdl-36303296

ABSTRACT

INTRODUCTION: We evaluated whether better cardiovascular health at midlife and improvement of cardiovascular health within midlife were associated with dementia risk. METHODS: Two longitudinal population-based studies were used: Atherosclerosis Risk in Communities (ARIC) (n = 11,460/visits at ages 54 and 60), and Age, Gene/Environment Susceptibility (AGES)-Reykjavik (n = 3907/visit at age 51). A cardiovascular health score (range 0-12/0-14, depending on diet availability) including six/seven items was calculated at each visit, with weight assigned to each item as poor (0), intermediate (1), or ideal (2). Cardiovascular health was defined as low (score 0-4/0-5), intermediate (5-7/6-9), or high (8-12/10-14). Incident dementia was ascertained through linkage to health records and with neuropsychological examinations. RESULTS: Midlife high compared to low cardiovascular health (hazard ratios [HRs]: for ARIC: 0.60 [95% confidence interval: 0.52, 0.69]); for AGES-Reykjavik: 0.83 [0.66, 0.99] and improvement of cardiovascular health score within midlife (HR per one-point increase: ARIC: 0.94 [0.92, 0.96]) were associated with lower dementia risk. DISCUSSION: Better cardiovascular health at midlife and improvement of cardiovascular health within midlife are associated with lower dementia risk. HIGHLIGHTS: Cardiovascular health and dementia were studied in two large cohort studies. Better cardiovascular health at midlife relates to lower dementia risk. Improvement of cardiovascular health within midlife relates to lower dementia risk. Promotion of cardiovascular health at midlife can help to reduce dementia risk.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Dementia , Humans , Middle Aged , Risk Factors , Dementia/epidemiology , Dementia/etiology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/complications , Cohort Studies , Heart Disease Risk Factors , Atherosclerosis/complications
12.
J Clin Periodontol ; 49(4): 322-334, 2022 04.
Article in English | MEDLINE | ID: mdl-34905804

ABSTRACT

AIM: We investigate if periodontal disease is prospectively associated with cerebrovascular and neurodegenerative markers of dementia and Alzheimer's pathology. MATERIALS AND METHODS: N = 1306 participants (Visit 5 mean age = 76.5 [standard deviation = 5.4] years) in the Atherosclerosis Risk in Communities study with completed dental exams at Visit 4 underwent brain magnetic resonance imaging scans at Visit 5 while N = 248 underwent positron emission tomography scans. Participants were classified as edentulous or, among the dentate, by the modified Periodontal Profile Class. Brain volumes were regressed on periodontal status in linear regressions. Cerebrovascular measures and ß-amyloid positivity were regressed on periodontal status in logistic regressions. RESULTS: Periodontal disease was not associated with brain volumes, microhaemorrhages, or elevated ß-amyloid. Compared with periodontally healthy individuals, odds ratios [95% confidence interval] for all-type infarcts were 0.37 [0.20, 0.65] for severe tooth loss and 0.56 [0.31, 0.99] for edentulous participants. CONCLUSIONS: Within the limitations of this study, periodontal disease was not associated with altered brain volumes, microhaemorrhages, or ß-amyloid positivity. Tooth loss was associated with lower odds of cerebral infarcts.


Subject(s)
Atherosclerosis , Periodontal Diseases , Tooth Loss , Aged , Amyloid beta-Peptides/metabolism , Atherosclerosis/complications , Atherosclerosis/diagnostic imaging , Brain/diagnostic imaging , Brain/metabolism , Humans , Neuroimaging , Periodontal Diseases/complications , Periodontal Diseases/diagnostic imaging , Tooth Loss/complications , Tooth Loss/diagnostic imaging
13.
Alzheimers Dement ; 18(11): 2176-2187, 2022 11.
Article in English | MEDLINE | ID: mdl-35089640

ABSTRACT

INTRODUCTION: We hypothesized that lower untreated systolic blood pressure (SBP) would be associated with a lower risk of dementia and death up to age 95. METHODS: SBP measured between 2000 and 2006 was evaluated in relationship to dementia risk and brain biomarkers from 2009-2020 (n = 177) in the Gingko Evaluation of Memory Study (GEMS), mean age 95 in 2020. Participants had measurements of brain amyloid beta (Aß) and repeat clinical-cognitive evaluations every 6 months. RESULTS: By 2020, only 9 of 177 patients (5%) were alive and cognitively unimpaired (CU). Mean SBP from 2000 to 2006 was 120 mm Hg for nine alive/CU, 125 mm Hg for alive/mild cognitive impairment (MCI), and 130 mm Hg for alive/dementia (P = .03). The amount of Aß was directly related to SBP levels. In multivariate analysis, Aß+ in 2009 and thinner cortex were significant predictors of dementia. Excluding Aß, SBP became a significant predictor of dementia. DISCUSSION: Low SBP untreated by antihypertensive medications was associated with significant decreased risk of dementia and less Aß.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Dementia , Humans , Aged, 80 and over , Amyloid beta-Peptides , Blood Pressure , Cognitive Dysfunction/psychology , Biomarkers
14.
Alzheimers Dement ; 18(4): 561-571, 2022 04.
Article in English | MEDLINE | ID: mdl-34310039

ABSTRACT

INTRODUCTION: A data-driven index of dementia risk based on magnetic resonance imaging (MRI), the Alzheimer's Disease Pattern Similarity (AD-PS) score, was estimated for participants in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: AD-PS scores were generated for 839 cognitively non-impaired individuals with a mean follow-up of 4.86 years. The scores and a hypothesis-driven volumetric measure based on several brain regions susceptible to AD were compared as predictors of incident cognitive impairment in different settings. RESULTS: Logistic regression analyses suggest the data-driven AD-PS scores to be more predictive of incident cognitive impairment than its counterpart. Both biomarkers were more predictive of incident cognitive impairment in participants who were White, female, and apolipoprotein E gene (APOE) ε4 carriers. Random forest analyses including predictors from different domains ranked the AD-PS scores as the most relevant MRI predictor of cognitive impairment. CONCLUSIONS: Overall, the AD-PS scores were the stronger MRI-derived predictors of incident cognitive impairment in cognitively non-impaired individuals.


Subject(s)
Alzheimer Disease , Atherosclerosis , Cognitive Dysfunction , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/epidemiology , Alzheimer Disease/genetics , Apolipoprotein E4/genetics , Atherosclerosis/diagnostic imaging , Atherosclerosis/epidemiology , Brain/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/genetics , Female , Humans , Magnetic Resonance Imaging
15.
Alzheimers Dement ; 18(4): 551-560, 2022 04.
Article in English | MEDLINE | ID: mdl-34482601

ABSTRACT

INTRODUCTION: Little is known about how antecedent vascular risk factor (VRF) profiles impact late-life brain health. METHODS: We examined baseline VRFs, and cognitive testing and neuroimaging measures (ß-amyloid [Aß] PET, MRI) in a diverse longitudinal cohort (N = 159; 50% African-American, 50% White) from Wake Forest's Multi-Ethnic Study of Atherosclerosis Core. RESULTS: African-Americans exhibited greater baseline Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham stroke risk profile (FSRP), and atherosclerotic cardiovascular disease risk estimate (ASCVD) scores than Whites. We observed no significant racial differences in Aß positivity, cortical thickness, or white matter hyperintensity (WMH) volume. Higher baseline VRF scores were associated with lower cortical thickness and greater WMH volume, and FSRP and CAIDE were associated with Aß. Aß was cross-sectionally associated with cognition, and all imaging biomarkers were associated with greater 6-year cognitive decline. DISCUSSION: Results suggest the convergence of multiple vascular and Alzheimer's processes underlying neurodegeneration and cognitive decline.


Subject(s)
Atherosclerosis , Cognitive Dysfunction , Atherosclerosis/diagnostic imaging , Biomarkers , Brain/diagnostic imaging , Cognition , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/epidemiology , Humans , Magnetic Resonance Imaging , Neuroimaging , Risk Factors
16.
Int J Mol Sci ; 23(19)2022 Oct 07.
Article in English | MEDLINE | ID: mdl-36233223

ABSTRACT

S-equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most biologically potent among all soy isoflavones and their metabolites. Soy isoflavones are phytoestrogens and exert their actions through estrogen receptor-ß. Epidemiological studies in East Asia, where soy isoflavones are regularly consumed, show that dietary isoflavone intake is inversely associated with cognitive decline and dementia; however, randomized controlled trials of soy isoflavones in Western countries did not generally show their cognitive benefit. The discrepant results may be attributed to S-equol production capability; after consuming soy isoflavones, 40-70% of East Asians produce S-equol, whereas 20-30% of Westerners do. Recent observational and clinical studies in Japan show that S-equol but not soy isoflavones is inversely associated with multiple vascular pathologies, contributing to cognitive impairment and dementia, including arterial stiffness and white matter lesion volume. S-equol has better permeability to the blood-brain barrier than soy isoflavones, although their affinity to estrogen receptor-ß is similar. S-equol is also the most potent antioxidant among all known soy isoflavones. Although S-equol is available as a dietary supplement, no long-term trials in humans have examined the effect of S-equol supplementation on arterial stiffness, cerebrovascular disease, cognitive decline, or dementia.


Subject(s)
Cognitive Dysfunction , Dementia , Gastrointestinal Microbiome , Isoflavones , Antioxidants , Cognitive Dysfunction/prevention & control , Dementia/prevention & control , Equol/metabolism , Estrogen Receptor beta , Humans , Isoflavones/metabolism , Isoflavones/pharmacology , Phytoestrogens/metabolism , Receptors, Estrogen
17.
J Stroke Cerebrovasc Dis ; 31(5): 106388, 2022 May.
Article in English | MEDLINE | ID: mdl-35193028

ABSTRACT

OBJECTIVE: Elevated carotid intima-media thickness (cIMT) and carotid plaque are markers of arterial injury and may be linked to structural brain injury. We hypothesized cIMT or presence of carotid plaque at midlife are associated with presence of infarcts and cerebral microbleeds, greater white matter hyperintensity (WMH) volume, and smaller regional brain volumes in late-life. METHODS: We included 1,795 Atherosclerosis Risk in Communities (ARIC) Study participants (aged 57±6 years, 57% female, 23% Black) with carotid ultrasounds in 1990-1992 and brain MRI scans in 2011-2013. Weighted linear regression was used for brain volume outcomes, while logistic regression was used for infarcts and cerebral microbleeds. RESULTS: After multivariable adjustments, the highest cIMT quintile was associated with smaller deep gray matter (ß [95% CI]: -0.11 [-0.22, -0.01]) and cortical volume in a temporal-parietal meta region of interest (ROI) (ß [95% CI]: -0.10 [-0.20, -0.01]) in late-life. Similarly, those with carotid plaque had smaller regional brain volumes than those without (ßs [95% CIs]: -0.05 [-0.12, 0.03] and -0.06 [-0.13, 0.01] for deep gray matter and temporal-parietal meta ROI). No significant relations were observed with WMH volume, infarcts, or cerebral microbleeds. CONCLUSION: Over a median follow-up of 21 years, greater midlife cIMT and presence of carotid plaque were associated with smaller deep gray matter volume and cortical volume in a meta ROI involving temporal and parietal lobe regions typically involved in neurodegeneration, including Alzheimer's disease, in later life. Contrary to our hypothesis, associations between measures of arterial injury and markers of vascular brain injury were null.


Subject(s)
Atherosclerosis , Carotid Artery Diseases , Plaque, Atherosclerotic , Atherosclerosis/complications , Biomarkers , Brain/diagnostic imaging , Carotid Artery Diseases/complications , Carotid Artery Diseases/diagnostic imaging , Carotid Intima-Media Thickness , Cerebral Hemorrhage/complications , Female , Humans , Infarction/complications , Magnetic Resonance Imaging , Male , Plaque, Atherosclerotic/complications , Risk Factors
18.
Alzheimer Dis Assoc Disord ; 34(3): 191-197, 2020.
Article in English | MEDLINE | ID: mdl-32483017

ABSTRACT

BACKGROUND: Norms for the Uniform Data Set Version 3 Neuropsychological Battery are available for cognitively normal individuals based on age, education, and sex; however, these norms do not include race. We provide expanded norms for African Americans and whites. METHODS: Data from 32 Alzheimer's Disease Centers (ADCs) and ADC affiliated cohorts with global Clinical Dementia Rating Scale (CDR) Dementia Staging Instrument scores of 0 were included. Descriptive statistics for each test were calculated by age, sex, race, and education. Multiple linear regressions were conducted to estimate the effect of each demographic variable; squared semipartial correlation coefficients measured the relative importance of variables. RESULTS: There were 8313 participants (16% African American) with complete demographic information, ranging from 6600 to 7885 depending on the test. Lower scores were found for older and less educated groups, and African Americans versus whites. Education was the strongest predictor for most tests, followed in order by age, race, and sex. Quadratic terms were significant for age and education, indicating some nonlinearity, but did not substantially increase R. CONCLUSIONS: Although race-based norms represent incomplete proxies for other sociocultural variables, the appropriate application of these norms is important given the potential to improve diagnostic accuracy and to reduce misclassification bias in cognitive disorders of aging such as Alzheimer disease.


Subject(s)
Aging , Black or African American/statistics & numerical data , Healthy Volunteers , Neuropsychological Tests , White People/statistics & numerical data , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Databases, Factual , Female , Humans , Male , Middle Aged , Neuropsychological Tests/standards , Neuropsychological Tests/statistics & numerical data , United States
19.
Alzheimers Dement ; 16(12): 1714-1733, 2020 12.
Article in English | MEDLINE | ID: mdl-33030307

ABSTRACT

Vascular contributions to cognitive impairment and dementia (VCID) are characterized by the aging neurovascular unit being confronted with and failing to cope with biological insults due to systemic and cerebral vascular disease, proteinopathy including Alzheimer's biology, metabolic disease, or immune response, resulting in cognitive decline. This report summarizes the discussion and recommendations from a working group convened by the National Heart, Lung, and Blood Institute and the National Institute of Neurological Disorders and Stroke to evaluate the state of the field in VCID research, identify research priorities, and foster collaborations. As discussed in this report, advances in understanding the biological mechanisms of VCID across the wide spectrum of pathologies, chronic systemic comorbidities, and other risk factors may lead to potential prevention and new treatment strategies to decrease the burden of dementia. Better understanding of the social determinants of health that affect risks for both vascular disease and VCID could provide insight into strategies to reduce racial and ethnic disparities in VCID.


Subject(s)
Brain/physiopathology , Cerebrovascular Disorders/physiopathology , Cognitive Dysfunction/physiopathology , Dementia, Vascular/physiopathology , Education , Aging/physiology , Biomarkers , Humans , National Heart, Lung, and Blood Institute (U.S.) , National Institute of Neurological Disorders and Stroke (U.S.) , United States
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