Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia

Wolters, Frank J.; Bruijn, Renée F.A.G. de; Hofman, Albert; Koudstaal, Peter J.; Ikram, M. Arfan

doi:10.1161/atvbaha.115.306768

Cited by 46 publications

(32 citation statements)

References 51 publications

(57 reference statements)

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“…It has been established that cerebral hypoperfusion and increased pulsatility index (PI) are associated with a clinical diagnosis of AD . More promising (for early detection considerations) is recent evidence suggesting that changes in cerebral perfusion are present long before clinical symptoms of AD are manifest. This evidence is promising because cerebral perfusion is much easier to assess than Aβ accumulation.…”

Section: Introductionmentioning

confidence: 99%

Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease

Alwatban

Murman

Bashford

2019

Journal of Neuroimaging

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BACKGROUND AND PURPOSE: A substantial overlap exists between declines in cerebral vasoreactivity (CVR) and symptomatic Alzheimer's disease (AD). CVR can be quantified using transcranial Doppler (TCD) measurement of cerebral blood flow velocities (CBFV) in the middle cerebral artery (MCA) with CO 2 as a vasodilatory stimulus. The breath-hold acceleration index (BHAI) is a new, more reliable measure of CVR developed recently in our laboratory. Our primary goal is to explore the possibility of using TCD for asymptomatic AD screening. METHODS:A pilot study population was divided into three groups: 9 healthy control subjects, 8 subjects identified as preclinical AD, and 10 patients diagnosed with prodromal or mild AD. Control subjects had a Clinical Dementia Rating (CDR) score of 0 without elevated amyloid-β (Aβ) on amyloid positron emission tomography (PET) imaging, preclinical AD subjects had CDR = 0 with elevated Aβ, and prodromal to mild AD subjects had CDR scores ࣙ.5 and elevated Aβ. CVR was calculated using two indices: the conventional breath-holding index (BHI) and the new BHAI. TCD parameters between the three groups were compared. RESULTS: BHAI was able to distinguish between 9 normal control subjects and 8 preclinical-AD subjects with high statistical significance (P < .001). BHI and pulsatility index were able only to distinguish AD from healthy and preclinical subjects (P < .001). CONCLUSIONS: In this exploratory pilot study, CVR was significantly decreased in preclinical, prodromal, and mild AD subjects as compared to the healthy group. Lower CVR in the preclinical AD group was detected using the new BHAI index but not the conventional BHI index.

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Section: Introductionmentioning

confidence: 99%

Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease

Alwatban

Murman

Bashford

2019

Journal of Neuroimaging

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“…Two important mechanisms for maintenance of proper and continuous cerebral perfusion are local vasoreactivity and autonomous nervous system function. Cerebral vasoreactivity has indeed been found to be associated with the risk of developing dementia in the general population [ 6 ], but the role of autonomous nervous system function in the onset of dementia has been less well studied.…”

Section: Introductionmentioning

confidence: 99%

Orthostatic Hypotension and the Long-Term Risk of Dementia: A Population-Based Study

et al. 2016

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BackgroundOrthostatic hypotension (OH) is a common cause of transient cerebral hypoperfusion in the population. Cerebral hypoperfusion is widely implicated in cognitive impairment, but whether OH contributes to cognitive decline and dementia is uncertain. We aimed to determine the association between OH and the risk of developing dementia in the general population.Methods and FindingsBetween 4 October 1989 and 17 June 1993, we assessed OH in non-demented, stroke-free participants of the population-based Rotterdam Study. OH was defined as a ≥20 mm Hg drop in systolic blood pressure (SBP) or ≥10 mm Hg drop in diastolic blood pressure (DBP) within 3 min from postural change. We furthermore calculated within participant variability in SBP related to postural change, expressed as coefficient of variation. Follow-up for dementia was conducted until 1 January 2014. We determined the risk of dementia in relation to OH and SBP variability, using a Cox regression model, adjusted for age; sex; smoking status; alcohol intake; SBP; DBP; cholesterol:high-density lipoprotein ratio; diabetes; body mass index; use of antihypertensive, lipid-lowering, or anticholinergic medication; and apolipoprotein E genotype. Finally, we explored whether associations varied according to compensatory increase in heart rate. Among 6,204 participants (mean ± standard deviation [SD] age 68.5 ± 8.6 y, 59.7% female) with a median follow-up of 15.3 y, 1,176 developed dementia, of whom 935 (79.5%) had Alzheimer disease and 95 (8.1%) had vascular dementia. OH was associated with an increased risk of dementia (adjusted hazard ratio [aHR] 1.15, 95% CI 1.00–1.34, p = 0.05), which was similar for Alzheimer disease and vascular dementia. Similarly, greater SBP variability with postural change was associated with an increased risk of dementia (aHR per SD increase 1.08, 95% CI 1.01–1.16, p = 0.02), which was similar when excluding those who fulfilled the formal criteria for OH (aHR 1.08, 95% CI 1.00–1.17, p = 0.06). The risk of dementia was particularly increased in those with OH who lacked a compensatory increase in heart rate (within lowest quartile of heart rate response: aHR 1.39, 95% CI 1.04–1.85, p-interaction = 0.05). Limitations of this study include potential residual confounding despite rigorous adjustments, and potentially limited generalisability to populations not of European descent.ConclusionsIn this population predominantly of European descent, OH was associated with an increase in long-term risk of dementia.

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“…A dose-response association between APOE genotypes and ischemic stroke has been shown in a systemic review and meta-analysis. 31 Other studies have shown that APOE genotypes were associated with cerebral vasoreactivity 32 and central arterial stiffening. 33 These findings suggested that the interaction between APOE genotypes and cerebral vascular changes needs to be considered in the disease process to be related to both APOE and VRFs.…”

Section: Discussionmentioning

confidence: 99%

Summative Effects of Vascular Risk Factors on the Progression of Alzheimer Disease

Lee

Liao

Lin

et al. 2019

J American Geriatrics Society

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OBJECTIVES To investigate the summative effects of vascular risk factors (VRFs) on the progression of Alzheimer disease (AD). DESIGN Longitudinal follow‐up cohort study. SETTING AD patients from two teaching hospitals in Taiwan with 3‐year follow‐ups. PARTICIPANTS A total of 330 AD patients with a mean age of 80.7 years, a mean Mini‐Mental State Examination (MMSE) score 18.7, and a mean Clinical Dementia Rating Sum of Boxes (CDRSB) score of 6.9. MEASUREMENTS All patients completed a clinically functional assessment and a neuropsychological test battery at baseline and yearly follow‐ups. The VRF burden was combined into a summative VRF index at baseline (ie, having one, two, or more VRFs); VRFs included coronary heart disease, cardiac arrhythmia, hypertension, cerebrovascular disease, diabetes mellitus, obesity, smoking, and physical inactivity. The generalized estimating equation (GEE) method was used to analyze the correlations between the VRFs and longitudinal MMSE and CDRSB changes. RESULTS The results of the GEE adjusted for age, years of education, sex, disease duration, baseline MMSE score, time, apolipoprotein E (APOE) ε4 carrier status, use of medications (acetylcholinesterase inhibitors or N‐methyl‐D‐aspartate receptor antagonists), and hospitalization rates and showed that patients with more than three VRFs had more rapid cognitive decline than patients without VRFs (MMSE, P = .02; CDRSB, P = .001) as well as patients with three or fewer VRFs (MMSE, P = .009; CDRSB, P = .02). Subsequent analyses of APOE ε4 carriers with more than three VRFs also showed their more rapid cognitive decline compared with patients without VRFs (MMSE, P = .02; CDRSB, P = .001) and patients with three or fewer VRFs (MMSE, P = .009; CDRSB, P = .02), but no significant difference was found in APOE ε4 noncarriers. CONCLUSION Multiple VRFs have summative effects on the progression of AD, especially in APOE ε4 carriers. J Am Geriatr Soc 68:129–136, 2019

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Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia

Cited by 46 publications

References 51 publications

Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease

Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease

Orthostatic Hypotension and the Long-Term Risk of Dementia: A Population-Based Study

Summative Effects of Vascular Risk Factors on the Progression of Alzheimer Disease

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