scholarly journals Association of midlife vascular risk and AD biomarkers with subsequent cognitive decline

Neurology ◽  
2020 ◽  
Vol 95 (23) ◽  
pp. e3093-e3103
Author(s):  
Corinne Pettigrew ◽  
Anja Soldan ◽  
Jiangxia Wang ◽  
Mei-Cheng Wang ◽  
Karissa Arthur ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Risk Score ◽  
Synergistic Effects ◽  
Vascular Risk Factor ◽  
Rate Of Change ◽  
Csf Biomarkers ◽  
Vascular Risk ◽  
Cognitively Normal ◽  
T Tau

ObjectiveTo determine whether vascular risk and Alzheimer disease (AD) biomarkers have independent or synergistic effects on cognitive decline and whether vascular risk is associated with the accumulation of AD pathology as measured by change in biomarkers over time.MethodsAt baseline, participants (n = 168) were cognitively normal and primarily middle-aged (mean 56.4 years, SD 10.9 years) and had both vascular risk factor status and proximal CSF biomarkers available. Baseline vascular risk was quantified with a composite vascular risk score reflecting the presence or absence of hypertension, hypercholesterolemia, diabetes, current smoking, and obesity. CSF biomarkers of β-amyloid (Aβ)1–42, total tau (t-tau), and phosphorylated tau (p-tau) were used to create dichotomous high and low AD biomarker groups (based on Aβ1–42 and tau). Linear mixed-effects models were used to examine change in a cognitive composite score (mean follow-up 13.9 years) and change in CSF biomarkers (mean follow-up 4.2 years).ResultsThere was no evidence of a synergistic relationship between the vascular risk score and CSF AD biomarkers and cognitive decline. Instead, the vascular risk score (estimate −0.022, 95% confidence interval [CI] −0.043 to −0.002, p = 0.03) and AD biomarkers (estimate −0.060, 95% CI −0.096 to −0.024, p = 0.001) were independently and additively associated with cognitive decline. In addition, the vascular risk score was unrelated to levels of or rate of change in CSF Aβ1–42, t-tau, or p-tau.ConclusionsThe results of this observational cohort study suggest that vascular risk and biomarkers of AD pathology, when measured in midlife, act along independent pathways and underscore the importance of accounting for multiple risk factors for identifying cognitively normal individuals at the greatest risk of cognitive decline.

scholarly journals Can cardiovascular risk management be improved by shared care with general practice to prevent cognitive decline following stroke/TIA? A feasibility randomised controlled trial (SERVED memory)

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
William J. Davison ◽  
Phyo K. Myint ◽  
Yoon K. Loke ◽  
Garth Ravenhill ◽  
David Turner ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Randomised Trial ◽  
Vascular Risk Factor ◽  
Vascular Risk ◽  
Risk Factor Management ◽  
Post Stroke ◽  
Observational Cohort

Abstract Background Cognitive impairment and dementia following cerebrovascular disease are increasingly common in the UK. One potential strategy to prevent post-stroke cognitive decline is multimodal vascular risk factor management. However, its efficacy remains uncertain and its application in vulnerable patients with incident cerebrovascular disease and early cognitive impairment has not been assessed. The primary aim of this study was to assess the feasibility of recruitment and retention of patients with early cognitive impairment post-stroke or transient ischaemic attack (TIA) to a trial of enhanced vascular risk factor management combining primary and secondary care. Methods In this single centre, open label trial adults with a recent stroke or TIA and mild cognitive impairment (MCI) were randomised 1:1 to a three-monthly multimodal vascular risk factor intervention jointly delivered by the trial team and General Practitioner (GP), or control (defined as usual care from the GP). Chosen risk factors were blood pressure (BP), total cholesterol, blood glucose (HbA1C) in those with diabetes, and heart rate and adequacy of anticoagulation in those with atrial fibrillation (AF). Similar patients with normal cognition were enrolled in an embedded observational cohort and also received usual care from the GP. Repeat cognitive screening was undertaken in all participants after 12 months. Results Seventy three participants were recruited to the randomised trial and 94 to the observational cohort (21.8% of those screened). From the randomised trial 35/73 (47.9%) dropped out before final follow-up. In all groups guideline based rates of risk factor control were mostly poor at baseline and did not significantly improve during follow-up. The observational cohort demonstrated greater decline in cognitive test scores at 12 months, with no difference between the randomised groups. Conclusions Recruitment to such a study was feasible, but retention of participants was difficult and generally poor rates of risk factor control suggested insufficient application of the intervention. Consequently, successful scaling up of the trial would require protocol changes with less reliance on primary care services. Any future trial should include participants with normal cognition post-stroke as they may be at greatest risk of cognitive decline. Trial registration ISRCTN, ISRCTN42688361. Registered 16 April 2015.

Association of Subjective Cognitive Decline with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Pathology in Cognitively Intact Older Adults: The CABLE Study

2021 ◽  
pp. 1-9
Author(s):  
Chen Wen ◽  
Yan-Lin Bi ◽  
Hao Hu ◽  
Shu-Yi Huang ◽  
Ya-Hui Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Subjective Cognitive Decline ◽  
Csf Biomarkers ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Increased Risk ◽  
T Tau

Background: Subjective cognitive decline (SCD) might occur at the early stages of dementia. Individuals with SCD have an increased risk of subsequent objective cognitive decline and greater rates of progression to dementia. Objective: We aimed to explore the associations between SCD and cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology in cognitively normal individuals. Methods: A total of 1,099 cognitively normal elders with available data on CSF biomarkers of AD pathology (Aβ 42, P-tau, and T-tau) were included in our analysis. Linear regression was used to examine the associations of SCD status and SCD severity with CSF biomarkers. Additionally, a review was conducted to discuss the associations between SCD and CSF biomarkers of AD pathology. Results: After adjustments for covariates, SCD and SCD severity showed significant associations with CSF Aβ 42 (SCD: β= –0.0003, p = 0.0263; SCD severity: β= –0.0004, p = 0.0046), CSF T-tau/Aβ 42 ratio (SCD: β= 0.1080, p = 0.1080; SCD severity: β= 0.1129, p = 0.0009) and CSF P-tau/Aβ 42 ratio (SCD: β= 0.0167, p = 0.0103; SCD severity: β= 0.0193, p = 0.0006) rather than T-tau and P-tau compared with cognitively normal individuals. In the review, a total of 28 studies were finally included after reviewing 174 articles. CSF Aβ 42 was lower in SCD than cognitively normal (CN) individuals, but higher than those with objective cognitive decline. However, CSF tau pathology showed no difference between SCD and CN. Conclusion: The results indicated that pathophysiological changes in CSF Aβ pathology occurred in individuals with SCD, which provide new insights into early intervention of AD.

scholarly journals Cardiorespiratory fitness alters the influence of a polygenic risk score on biomarkers of AD

Neurology ◽  
2017 ◽  
Vol 88 (17) ◽  
pp. 1650-1658 ◽  
Author(s):  
Stephanie A. Schultz ◽  
Elizabeth A. Boots ◽  
Burcu F. Darst ◽  
Henrik Zetterberg ◽  
Kaj Blennow ◽  
...  
Keyword(s):  
Cardiorespiratory Fitness ◽  
Risk Score ◽  
Csf Biomarkers ◽  
Polygenic Risk Score ◽  
Regression Analyses ◽  
Cross Sectional ◽  
Polygenic Risk ◽  
Β Amyloid ◽  
Adverse Influence ◽  
T Tau

Objective:To examine whether a polygenic risk score (PRS) derived from APOE4, CLU, and ABCA7 is associated with CSF biomarkers of Alzheimer disease (AD) pathology and whether higher cardiorespiratory fitness (CRF) modifies the association between the PRS and CSF biomarkers.Methods:Ninety-five individuals from the Wisconsin Registry for Alzheimer's Prevention were included in these cross-sectional analyses. They were genotyped for APOE4, CLU, and ABCA7, from which a PRS was calculated for each participant. The participants underwent lumbar puncture for CSF collection. β-Amyloid 42 (Aβ42), Aβ40, total tau (t-tau), and phosphorylated tau (p-tau) were quantified by immunoassays, and Aβ42/Aβ40 and tau/Aβ42 ratios were computed. CRF was estimated from a validated equation incorporating sex, age, body mass index, resting heart rate, and self-reported physical activity. Covariate-adjusted regression analyses were used to test for associations between the PRS and CSF biomarkers. In addition, by including a PRS×CRF term in the models, we examined whether these associations were modified by CRF.Results:A higher PRS was associated with lower Aβ42/Aβ40 (p < 0.001), higher t-tau/Aβ42 (p = 0.012), and higher p-tau/Aβ42 (p = 0.040). Furthermore, we observed PRS × CRF interactions for Aβ42/Aβ40 (p = 0.003), t-tau/Aβ42 (p = 0.003), and p-tau/Aβ42 (p = 0.001). Specifically, the association between the PRS and these CSF biomarkers was diminished in those with higher CRF.Conclusions:In a late-middle-aged cohort, CRF attenuates the adverse influence of genetic vulnerability on CSF biomarkers. These findings support the notion that increased cardiorespiratory fitness may be beneficial to those at increased genetic risk for AD.

Increased CAIDE dementia risk, cognition, CSF biomarkers, and vascular burden in healthy adults

Neurology ◽  
2018 ◽  
Vol 91 (3) ◽  
pp. e217-e226 ◽  
Author(s):  
Mirian Ecay-Torres ◽  
Ainara Estanga ◽  
Mikel Tainta ◽  
Andrea Izagirre ◽  
Maite Garcia-Sebastian ◽  
...  
Keyword(s):  
Linear Models ◽  
Global Memory ◽  
Csf Biomarkers ◽  
Cognitively Normal ◽  
Project Study ◽  
Dementia Risk ◽  
Premorbid Intelligence ◽  
T Tau ◽  
Vascular Burden

ObjectiveTo investigate the cognitive profile of healthy individuals with increased Cardiovascular Risk Factors, Aging and Dementia (CAIDE) dementia risk score and to explore whether this association is related to vascular burden and CSF biomarkers of amyloidosis and neurodegeneration.MethodCognitively normal participants (mean age 57.6 years) from the Gipuzkoa Alzheimer Project study were classified as having high risk (HR; n = 82) or low risk (LR; n = 293) for dementia according to a CAIDE score cutoff of 9. Cognitive composites were compared between groups. We explored using generalized linear models the role ofAPOEgenotype, MRI white matter hyperintensities (WMH), and CSF (n = 218) levels of β-amyloid1-42(Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) in the association between CAIDE score and cognition.ResultsHR participants obtained lower scores on executive function (EF) (p= 0.001) and visual perception and construction (VPC) (p< 0.001) composites. EF composite was associated with CAIDE score × p-tau (p= 0.001), CAIDE score × t-tau (p= 0.001), and WMH (p= 0.003). VPC composite was associated withAPOE(p= 0.001), Aβ1–42(p= 0.004), the interaction APOE × Aβ1–42(p= 0.003), and WMH (p= 0.004). Performance on global memory was associated with Aβ1–42(p= 0.006),APOE(p= 0.008), and their interaction (p= 0.006). Analyses were adjusted for age, education, sex, premorbid intelligence, and stress.ConclusionHealthy participants at increased dementia risk based on CAIDE scores show lower performance in EF and VPC. This difference is related toAPOE, WMH, and Alzheimer biomarkers.

scholarly journals Association of amyloid-β CSF/PET discordance and tau load 5 years later

Neurology ◽  
2020 ◽  
Vol 95 (19) ◽  
pp. e2648-e2657 ◽  
Author(s):  
Juhan Reimand ◽  
Lyduine Collij ◽  
Philip Scheltens ◽  
Femke Bouwman ◽  
Rik Ossenkoppele ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Tau Pathology ◽  
Cognitively Normal ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Tau Pet

ObjectiveTo investigate the association between discordant β-amyloid (Aβ) PET and CSF biomarkers at baseline and the emergence of tau pathology 5 years later.MethodsWe included 730 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants without dementia (282 cognitively normal, 448 mild cognitive impairment) with baseline [18F]florbetapir PET and CSF Aβ42 available. Aβ CSF/PET status was determined at baseline using established cutoffs. Longitudinal data were available for [18F]florbetapir (Aβ) PET (baseline to 4.3 ± 1.9 years), CSF (p)tau (baseline to 2.0 ± 0.1 years), cognition (baseline to 4.3 ± 2.0 years), and [18F]flortaucipir (tau) PET (measured 5.2 ± 1.2 years after baseline to 1.6 ± 0.7 years later). We used linear mixed modeling to study the association between Aβ CSF/PET status and tau pathology measured in CSF or using PET. We calculated the proportion of CSF+/PET− participants who during follow-up (1) progressed to Aβ CSF+/PET+ or (2) became tau-positive based on [18F]flortaucipir PET.ResultsAβ CSF+/PET+ (n = 318) participants had elevated CSF (p)tau levels and worse cognitive performance at baseline, while CSF+/PET− (n = 80) participants were overall similar to the CSF−/PET− (N = 306) group. Five years after baseline, [18F]flortaucipir PET uptake in the CSF+/PET− group (1.20 ± 0.13) did not differ from CSF−/PET− (1.18 ± 0.08, p = 0.69), but was substantially lower than CSF+/PET+ (1.48 ± 0.44, p < 0.001). Of the CSF+/PET− participants, 21/64 (33%) progressed to Aβ CSF+/PET+, whereas only one (3%, difference p < 0.05) became tau-positive based on [18F]flortaucipir PET.ConclusionsAβ load detectable by both CSF and PET seems to precede substantial tau deposition. Compared to participants with abnormal Aβ levels on both PET and CSF, the CSF+/PET− group has a distinctly better prognosis.

scholarly journals Functional network integrity presages cognitive decline in preclinical Alzheimer disease

Neurology ◽  
2017 ◽  
Vol 89 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Rachel F. Buckley ◽  
Aaron P. Schultz ◽  
Trey Hedden ◽  
Kathryn V. Papp ◽  
Bernard J. Hanseeuw ◽  
...  
Keyword(s):  
Older Adults ◽  
Functional Connectivity ◽  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Cognitive Networks ◽  
Rate Of Change ◽  
Control Networks ◽  
Clinically Normal ◽  
And Control

Objective:To examine the utility of resting-state functional connectivity MRI (rs-fcMRI) measurements of network integrity as a predictor of future cognitive decline in preclinical Alzheimer disease (AD).Methods:A total of 237 clinically normal older adults (aged 63–90 years, Clinical Dementia Rating 0) underwent baseline β-amyloid (Aβ) imaging with Pittsburgh compound B PET and structural and rs-fcMRI. We identified 7 networks for analysis, including 4 cognitive networks (default, salience, dorsal attention, and frontoparietal control) and 3 noncognitive networks (primary visual, extrastriate visual, motor). Using linear and curvilinear mixed models, we used baseline connectivity in these networks to predict longitudinal changes in preclinical Alzheimer cognitive composite (PACC) performance, both alone and interacting with Aβ burden. Median neuropsychological follow-up was 3 years.Results:Baseline connectivity in the default, salience, and control networks predicted longitudinal PACC decline, unlike connectivity in the dorsal attention and all noncognitive networks. Default, salience, and control network connectivity was also synergistic with Aβ burden in predicting decline, with combined higher Aβ and lower connectivity predicting the steepest curvilinear decline in PACC performance.Conclusions:In clinically normal older adults, lower functional connectivity predicted more rapid decline in PACC scores over time, particularly when coupled with increased Aβ burden. Among examined networks, default, salience, and control networks were the strongest predictors of rate of change in PACC scores, with the inflection point of greatest decline beyond the fourth year of follow-up. These results suggest that rs-fcMRI may be a useful predictor of early, AD-related cognitive decline in clinical research settings.

scholarly journals Interactive Associations of Neuropsychiatry Inventory-Questionnaire Assessed Sleep Disturbance and Vascular Risk on Alzheimer’s Disease Stage Progression in Clinically Normal Older Adults

2021 ◽  
Vol 13 ◽  
Author(s):  
Omonigho M. Bubu ◽  
Ellita T. Williams ◽  
Ogie Q. Umasabor-Bubu ◽  
Sonya S. Kaur ◽  
Arlener D. Turner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Sleep Disturbance ◽  
Risk Score ◽  
Disease Stage ◽  
Vascular Risk ◽  
Cvd Risk ◽  
Stage Progression

Background: To determine whether sleep disturbance (SD) and vascular-risk interact to promote Alzheimer’s disease (AD) stage-progression in normal, community-dwelling older adults and evaluate their combined risk beyond that of established AD biomarkers.Methods: Longitudinal data from the National Alzheimer’s Coordinating Center Uniform-Dataset. SD data (i.e., SD+ vs. SD-), as characterized by the Neuropsychiatric Inventory-Questionnaire, were derived from 10,600 participants at baseline, with at-least one follow-up visit. A subset (n = 361) had baseline cerebrospinal fluid (CSF) biomarkers and MRI data. The Framingham heart study general cardiovascular disease (FHS-CVD) risk-score was used to quantify vascular risk. Amnestic mild cognitive impairment (aMCI) diagnosis during follow-up characterized AD stage-progression. Logistic mixed-effects models with random intercept and slope examined the interaction of SD and vascular risk on prospective aMCI diagnosis.Results: Of the 10,600 participants, 1,017 (9.6%) reported SD and 6,572 (62%) were female. The overall mean (SD) age was 70.5 (6.5), and follow-up time was 5.1 (2.7) years. SD and the FHS-CVD risk-score were each associated with incident aMCI (aOR: 1.42 and aOR: 2.11, p &lt; 0.01 for both). The interaction of SD and FHS-CVD risk-score with time was significant (aOR: 2.87, p &lt; 0.01), suggesting a synergistic effect. SD and FHS-CVD risk-score estimates remained significantly associated with incident aMCI even after adjusting for CSF (Aβ, T-tau, P-tau) and hippocampal volume (n = 361) (aOR: 2.55, p &lt; 0.01), and approximated risk-estimates of each biomarker in the sample where data was available.Conclusions: Clinical measures of sleep and vascular risk may complement current AD biomarkers in assessing risk of cognitive decline in older adults.

Abstract TP422: High Pulse Pressure and Risk of Stroke Recurrence in Patients With Tia

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Maria C Zurru ◽  
Claudia Alonzo ◽  
Laura Brescacin ◽  
Santiago Pigretti ◽  
Pedro Colla Machado ◽  
...  
Keyword(s):  
Vascular Disease ◽  
Pulse Pressure ◽  
Clinical Decision Making ◽  
Vascular Risk Factor ◽  
Clinical Decision ◽  
Stroke Recurrence ◽  
Vascular Risk ◽  
High Pulse ◽  
And Control

Introduction: stroke recurrence in patients with TIA is one of the most frustrating medical situations and it is very important to identify strong predictors of stroke recurrence to enable practitioners to take clinical decisions Hypothesis: to evaluate the relationship between pulse pressure (PP), a marker of vascular disease, and the risk of stroke recurrence in patients with TIA. Methods: TIA patients were prospectively included in a multidisciplinary secondary stroke prevention program. Pre-stroke vascular risk factor profile and control were obtained from electronic medical records. Stroke recurrence was analyzed after five years of follow up. For the purpose of the analysis, three groups were defined according to pre-stroke PP: < 60, 60-69 and > 70 mmHg. Results: 357 patients (mean age 75±10 years, 55% females) were included. Vascular risk factors profile: hypertension 83%, dislipidemia 74%, obesity 54%, smoking 41%, diabetes 12%, AF 12%, CKD 28%, CHD 18%. Mean SBP was 130 mmHg and DBP 80 mmHg; 78% was receiving antihypertensives, 47% statins, 43% antiplatelets and 9% anticoagulants before the event. There was a direct relationship between pre-stroke PP and stroke recurrence during follow-up (figure). Conclusion: PP is related to higher burden of vascular disease, mainly an increase in arterial stiffness, which might be a key element in clinical decision making in the setting of stroke recurrence prevention.

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