scholarly journals Hypertension and Hypercholesterolemia Modify Dementia Risk in Relation to APOE ɛ4 Status

2021 ◽  
pp. 1-12
Author(s):  
Jagan A. Pillai ◽  
Kou Lei ◽  
James Bena ◽  
Lisa Penn ◽  
James B. Leverenz

Background: There is significant interest in understanding the role of modifiable vascular risk factors contributing to dementia risk across age groups. Objective: Risk of dementia onset was assessed in relation to vascular risk factors of hypertension and hypercholesterolemia among cognitively normal APOE ɛ4 carriers and non-carriers. Methods: In a sample of prospectively characterized longitudinal cohort from the National Alzheimer’s Coordinating Center database, 9,349 participants met criteria for normal cognition at baseline, had a CDR-Global (CDR-G) score of zero, and had concomitant data on APOE ɛ4 status and medical co-morbidities including histories of hypertension and hypercholesterolemia. Multivariable Cox proportional hazards models adjusted for well-known potential confounders were used to compare dementia onset among APOE ɛ4 carriers and non-carriers by young (≤65 years) and old (>  65 year) age groups. Results: 519 participants converted to dementia within an average follow up of 5.97 years. Among older APOE ɛ4 carriers, hypercholesterolemia was related to lower risk of dementia (HR (95% CI), 0.68 (0.49–0.94), p = 0.02). Among older APOE ɛ4 non-carriers, hypertension was related to higher risk of dementia (HR (95% CI), 1.44 (1.13–1.82), p = 0.003). These results were corroborated among a subset with autopsy data characterizing underlying neuropathology. Among younger participants, vascular risk factors did not impact dementia risk, likely from a lower frequency of vascular and Alzheimer’s as etiologies of dementia among this cohort. Conclusion: A history of hypercholesterolemia related to a lower risk of dementia among older APOE ɛ4 carriers, while hypertension related to a higher risk of dementia among older APOE ɛ4 non-carriers.

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Rebecca F Gottesman ◽  
Aozhou Wu ◽  
Josef Coresh ◽  
Clifford R Jack ◽  
David S Knopman ◽  
...  

Background: Midlife vascular risk factors (MVRF) are associated with incident dementia. Similarly, amyloid β(Aβ) and neurodegeneration (e.g.brain volumes), as parts of the Alzheimer’s Disease (AD) ATN framework, are associated with cognition. Whether vascular and AD-associated factors contribute to dementia independently or interact synergistically to reduce cognitive ability is not well understood. Methods: Recruited from 3 U.S. communities, ARIC-PET participants were followed from 1987-89 (45-64 yo) through 2016-17 (74-94 yo). Cognition was evaluated in 2011-13 (ages 69-88), and twice more, every 2-3 years. In 2011-13, nondemented ARIC-PET participants had a brain MRI, with measurement of white matter hyperintensities (WMH) and brain volumes, with florbetapir (Aβ) PET scans in 2012-14; global cortical standardized uptake value ratio (SUVR) was log-transformed and standardized. Dementia was classified by expert review, as well as phone and medical record surveillance. The relative contributions of vascular risk (MVRF, WMH volume) and AD pathology (elevated Aβ SUVR, smaller AD signature region volumes) to incident dementia were evaluated with Cox proportional hazards regression. Results: In 298 individuals, 36 developed dementia. In models with key MVRF, demographics, and Aβ SUVR, hypertension and Aβ each independently predicted dementia risk (per SD of Aβ SUVR: HR 2.57, 95% CI 1.72-3.84; hypertension: HR 2.57, 95% CI 1.16-5.67), but didn’t interact on dementia risk. WMH (per SD: HR 1.51, 95% CI 1.03-2.20) and Aβ SUVR (per SD: HR 2.52, 95% CI 1.83-3.47) each contributed to incident dementia but WMH lost significance when MVRF were added to the model. Smaller AD signature regions were associated with incident dementia, independent of Aβ SUVR, and remained significant after adjustment for MVRF (HR per SD 2.18, 95% CI 1.18-4.01). Conclusions: Midlife hypertension and late-life Aβ independently contribute to dementia risk, but don’t synergize on a multiplicative scale. Neurodegeneration (e.g.smaller AD signature region volume) is also associated with incident dementia, independent of Aβ and MVRF. Multiple pathways leading to dementia should be considered when evaluating risk factors and interventions to reduce the burden of dementia.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Michael P Lerario ◽  
Alexander E Merkler ◽  
Gino Gialdini ◽  
Neal S Parikh ◽  
Gary L Bernardini ◽  
...  

Introduction: The long-term cerebrovascular consequences of hypertensive encephalopathy (HE) are poorly understood. Therefore, we aimed to measure the risk of stroke following HE. Methods: We identified all adult patients discharged from nonfederal acute care hospitals between 2005 and 2013 in New York with a primary ICD-9-CM discharge diagnosis of HE (437.2). Only patients who underwent magnetic resonance imaging were included to reduce the likelihood of misclassification error. Patients with all other forms of hypertension (401-405), without concomitant codes for HE or cerebrovascular disease (430-438), served as controls. The primary outcome was incident stroke (431, 433.x1, 434.x1, or 436 in the absence of hemorrhage, trauma, or rehabilitation codes). Kaplan-Meier survival analysis was used to calculate cumulative rates of incident stroke and Cox proportional hazards analysis was used to determine the association between HE and incident stroke while adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index. Results: We identified 1,386 patients with HE and 2,869,873 with hypertension. Over a mean follow-up period of 3.3 (+/-1.8) years, we identified 66,594 ischemic and 12,343 hemorrhagic strokes. After 5 years, the cumulative rate of stroke was 7.8% (95% CI, 6.2-9.9%) in patients with HE and 3.2% (95% CI, 3.2-3.2%; P<0.001 for the log-rank test) in patients with any other hypertensive disease. After adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index, HE was independently associated with incident stroke (hazard ratio, 1.9; 95% CI, 1.5-2.4) as compared to controls. This association was similar when considering ischemic and hemorrhagic stroke separately. Conclusions: Patients discharged after HE face a higher long-term risk of subsequent stroke than patients without prior neurological complications of hypertension.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Benjamin R Kummer ◽  
Ashley E Aaroe ◽  
Hooman Kamel ◽  
Costantino Iadecola ◽  
Babak B Navi

Introduction: Cerebral ischemia and vascular risk factors are associated with the development of Alzheimer disease (AD). While Parkinson disease (PD) is also a common neurodegenerative condition, the relationship between ischemic stroke and PD remains unclear. Some evidence suggests a shared pathogenic pathway between both diseases. Methods: We used inpatient and outpatient claims data from 2008-2014 in a 5% sample of Medicare beneficiaries ≥66 years of age. Our variables of interest were: 1) a hospital-based diagnosis of ischemic stroke and 2) an outpatient or hospital-based diagnosis of idiopathic PD. Previously validated ICD-9-CM code algorithms were used to identify all diagnoses. We used Cox proportional hazards modeling to characterize the relationship between ischemic stroke and PD, while adjusting for demographics and vascular risk factors. We assessed both the association between PD and subsequent stroke, as well as stroke and subsequent PD. In a separate but identically designed set of analyses, we characterized the relationship between ischemic stroke and AD as a point of comparison. Results: Our analysis encompassed nearly 1.6 million patients with a mean age of 73(+/- 8) years, of whom 57% were female. The annual incidence of ischemic stroke was 1.75% (95% confidence interval [CI], 1.67-1.85%) after a diagnosis of PD versus 0.96% (95% CI, 0.96-0.97%) in those without PD (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.19-1.32). In contrast, the annual incidence of ischemic stroke was 1.96% (95% CI, 1.89-2.03%) after a diagnosis of AD versus 0.96% (95% CI, 0.96-0.97%) in those without AD (aHR, 0.98; 95% CI, 0.95-1.02). The annual incidence of PD was 0.97% (95% CI, 0.92-1.03%) after ischemic stroke versus 0.39% (95% CI, 0.38-0.39%) in those without ischemic stroke (aHR, 1.62; 95% CI, 1.53-1.72). In contrast, the annual incidence of AD was 3.66% (95% CI, 3.56-3.78%) after a diagnosis of ischemic stroke versus 1.17% (95% CI, 1.16-1.17%) in those without ischemic stroke (aHR, 1.67; 95% CI, 1.61-1.72). Conclusions: Among Medicare beneficiaries, the relationships between stroke and PD were similar to those between stroke and AD. As in AD, a link may exist between cerebrovascular disease and PD.


Neurology ◽  
2019 ◽  
Vol 92 (14) ◽  
pp. e1624-e1633 ◽  
Author(s):  
Ruth Ann Marrie ◽  
Allan Garland ◽  
Stephen Allan Schaffer ◽  
Randy Fransoo ◽  
Stella Leung ◽  
...  

ObjectiveTo compare the risk of incident acute myocardial infarction (AMI) in the multiple sclerosis (MS) population and a matched population without MS, controlling for traditional vascular risk factors.MethodsWe conducted a retrospective matched cohort study using population-based administrative (health claims) data in 2 Canadian provinces, British Columbia and Manitoba. We identified incident MS cases using a validated case definition. For each case, we identified up to 5 controls without MS matched on age, sex, and region. We compared the incidence of AMI between cohorts using incidence rate ratios (IRR). We used Cox proportional hazards regression to compare the hazard of AMI between cohorts adjusting for sociodemographic factors, diabetes, hypertension, and hyperlipidemia. We pooled the provincial findings using meta-analysis.ResultsWe identified 14,565 persons with MS and 72,825 matched controls. The crude incidence of AMI per 100,000 population was 146.2 (95% confidence interval [CI] 129.0–163.5) in the MS population and 128.8 (95% CI 121.8–135.8) in the matched population. After age standardization, the incidence of AMI was higher in the MS population than in the matched population (IRR 1.18; 95% CI 1.03–1.36). After adjustment, the hazard of AMI was 60% higher in the MS population than in the matched population (hazard ratio 1.63; 95% CI 1.43–1.87).ConclusionThe risk of AMI is elevated in MS, and this risk may not be accounted for by traditional vascular risk factors.


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Todd M Brown ◽  
Joshua Richman ◽  
Vera Bittner ◽  
Cora E Lewis ◽  
Jenifer Voeks ◽  
...  

Background: Some individuals classified as having metabolic syndrome (MetSyn) are centrally obese while others are not with unclear implications for cardiovascular (CV) risk. Methods: REGARDS is following 30,239 individuals ≥45 years of age living in 48 states recruited from 2003-7. MetSyn risk factors were defined using the AHA/NHLBI/IDF harmonized criteria with central obesity being defined as ≥88 cm in women and ≥102 cm in men. Participants with and without central obesity were stratified by whether they met >2 or ≤2 of the other 4 MetSyn criteria, resulting in the creation of 4 groups. To ascertain CV events, participants are telephoned every 6 months with expert adjudication of potential events following national consensus recommendations and based on medical records, death certificates, and interviews with next-of-kin or proxies. Acute coronary heart disease (CHD) was defined as definite or probable myocardial infarction or acute CHD death. To determine the association between these 4 groups and incident acute CHD, we constructed Cox proportional hazards models in those free of CHD at baseline by race/gender group, adjusting for sociodemographic variables. Results: A total of 20,018 individuals with complete data on MetSyn components were free of baseline CHD. Mean age was 64+/−9 years, 58% were women, and 42% were African American. Over a mean follow-up of 3.4 (maximum 5.9) years, there were 442 acute CHD events. In the non-centrally obese with>2 other risk factors, risk for CHD was higher for all but AA men, though significant only for white men. In contrast, in the centrally obese with >2 other risk factors, risk was doubled for women, but only non-significantly and modestly increased for men. Only AA women with central obesity and ≤2 other risk factors had increased CHD risk (Table). Conclusion: The CHD risk associated with the MetSyn varies by the presence of central obesity as well as the race and gender of the individual.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Tamara Strohm ◽  
Russell Cerejo ◽  
Jason Mathew ◽  
Irene Katzan ◽  
Ken Uchino

Introduction: Intracranial atherosclerosis has been well studied in the aging population, much less is known about atherosclerotic stenosis in the young. Clinicians seek to control traditional vascular risk factors in this population, but differences in patterns of stenosis may call for varied treatment approaches. This study sought to compare age to the distribution of vessel involvement in patients with moderate-severe intracranial stenosis. Methods: This is a retrospective cohort study of patients with intracranial stenosis seen in the stroke clinic of a tertiary center from 2008-2013. Inclusion criteria were moderate-severe intracranial stenosis clinically felt to be due to atherosclerosis with ≥3 traditional vascular risk factors. Patients with other mechanisms of intracranial stenosis were excluded. Stenosis location and severity were based on cerebral angiography, CTA, or MRA. Patients were divided into young (< 50 yr), middle-age (51-64 yr), or older (≥ 65 yr). All 69 patients ≤50 yr were included; a random sample of 69 patients > 50 were selected for this analysis. Results: There were similar rates of vascular risk factors except HTN, which was less common in the young group (81.2% young, 100% middle, 96.8% older, p=0.0006). The location of stenoses varied by age category. Older patients had more posterior circulation involvement compared to the younger groups (p = 0.046), with more frequent involvement of vertebral and basilar arteries (p = 0.012) (Table). The occurrence of stenosis in the distal ICA and MCA vessels were similar among age groups. The frequency of ACA stenosis was highest in the young category (p = 0.026). Conclusion: There are differences in anatomic locations of presumed intracranial atherosclerosis across age groups with older patients (> 65 yrs) having a higher rate of posterior circulation disease. This suggests potential differences in pathophysiological mechanisms. These findings warrant further investigation.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Zuber S Ali ◽  
Danielle M Greere ◽  
Robyn L Shearer ◽  
Syed Ali Gardezi ◽  
Arshad Jahangir

Introduction: Androgen suppression therapy for prostate cancer is controversial due to adverse fatal and non-fatal cardiovascular outcomes reported in some studies. However, effects of androgen suppression on stroke have not been fully assessed in the elderly. Methods: Patients diagnosed with prostate cancer during 2007-2013 in a large community-based healthcare system were identified from the Cancer Registry, electronic records, and billing codes. Those who underwent androgen suppression therapy with Gonadotropin-releasing hormone agonist (GnRH) were propensity-matched to patients treated without androgen suppression therapy by age at cancer diagnosis, race/ethnicity, disease stage and outcome, body mass index and use of surgery, radiation, and chemotherapy. Tests of independence and Cox proportional hazards models were used to examine effects of hormone therapy on acute myocardial infarction (AMI), stroke, and mortality outcomes. Models also adjusted for patient comorbidities. Results: A total of 1282 patients and 641 matched-pairs were identified, with mean diagnosis age of 69 yr and follow-up period of 3.05 yr. Effects of androgen suppression therapy on AMI (P=0.051) and stroke (P=0.062) were of marginal to non-significance, but adjusted-odds of death and combined AMI, stroke, and death were 1.61 times (P=0.002; odds ratio [OR] 95% CI: 1.19-2.18) and 1.70 times (P<0.001; OR 95% CI: 1.26-2.28) greater, respectively, for men with than without androgen suppression. An interaction of androgen suppression and age-group (<65 yr, 65-74 yr, >74 yr) was discovered for combined outcomes, suggesting increased probability of AMI, stroke, and/or death with age (8.6-20.0%; P=0.003) for patients without androgen suppression but elevated risk of outcomes across all age groups (18.3-22.4%; P=0.546) for men treated with androgen suppression therapy. Conclusion: Endogenous androgen suppression presents elevated risk of combined cardiovascular and death outcomes, especially for men <65 yr.


Neurology ◽  
2019 ◽  
Vol 93 (24) ◽  
pp. e2247-e2256 ◽  
Author(s):  
Miguel Arce Rentería ◽  
Jet M.J. Vonk ◽  
Gloria Felix ◽  
Justina F. Avila ◽  
Laura B. Zahodne ◽  
...  

ObjectiveTo investigate whether illiteracy was associated with greater risk of prevalent and incident dementia and more rapid cognitive decline among older adults with low education.MethodsAnalyses included 983 adults (≥65 years old, ≤4 years of schooling) who participated in a longitudinal community aging study. Literacy was self-reported (“Did you ever learn to read or write?”). Neuropsychological measures of memory, language, and visuospatial abilities were administered at baseline and at follow-ups (median [range] 3.49 years [0–23]). At each visit, functional, cognitive, and medical data were reviewed and a dementia diagnosis was made using standard criteria. Logistic regression and Cox proportional hazards models evaluated the association of literacy with prevalent and incident dementia, respectively, while latent growth curve models evaluated the effect of literacy on cognitive trajectories, adjusting for relevant demographic and medical covariates.ResultsIlliterate participants were almost 3 times as likely to have dementia at baseline compared to literate participants. Among those who did not have dementia at baseline, illiterate participants were twice as likely to develop dementia. While illiterate participants showed worse memory, language, and visuospatial functioning at baseline than literate participants, literacy was not associated with rate of cognitive decline.ConclusionWe found that illiteracy was independently associated with higher risk of prevalent and incident dementia, but not with a more rapid rate of cognitive decline. The independent effect of illiteracy on dementia risk may be through a lower range of cognitive function, which is closer to diagnostic thresholds for dementia than the range of literate participants.


2019 ◽  
Vol 48 (2) ◽  
pp. 240-249 ◽  
Author(s):  
Alpesh Amin ◽  
Allison Keshishian ◽  
Oluwaseyi Dina ◽  
Amol Dhamane ◽  
Anagha Nadkarni ◽  
...  

AbstractAtrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) vs warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban–warfarin, 18,131 dabigatran–warfarin, and 55,359 rivaroxaban–warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59–0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73–0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72–1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57–0.67; NCO: HR: 0.64; 95% CI 0.60–0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71–0.89; NCO: HR: 0.84; 95% CI 0.76–0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02–1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99–1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin.


Author(s):  
L.M. Bonner ◽  
A. Hanson ◽  
G. Robinson ◽  
E. Lowy ◽  
S. Craft

Dementia prevention is highly important. Improved control of vascular risk factors has the potential to decrease dementia risk, but may be difficult. Therefore, we developed and piloted a care management protocol for Veterans at risk for dementia. We enrolled 32 Veterans with diabetes and hypertension, at least one of which was poorly controlled, and cognitive impairment. Participants were randomly assigned to a 6-month care management intervention or to usual care. At enrollment, 6-months and 12-months, we assessed cognitive performance, mood, and diabetes and hypertension control. At follow-up, diastolic blood pressure was lower in intervention participants at 6 months (p=.041) and 12 months (p=.022); hemoglobin A1c, global mental status and mood did not differ between groups. Recall of a distractor list (p=.006) and logical memory long-delay recall (p=.036) were better at 6 months in the intervention group (p=.006). Care management may contribute to improved control of dementia risk factors.


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