Associations of Pulse and Blood Pressure with Hippocampal Volume by APOE and Cognitive Phenotype: The Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Ngwa, Julius S.; Fungwe, Thomas V.; Ntekim, Oyonumo; Allard, Joanne; Johnson, Stephen E.; Castor, Chimene; Graham, Lennox; Nadarajah, Sheeba; Gillum, Richard F.; Obisesan, Thomas O.; Initiative, Alzheimer’s Disease Neuroimaging

doi:10.1159/000486955

Cited by 8 publications

(8 citation statements)

References 59 publications

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“…Increased vascular resistance promoted by amyloid deposition and the need for higher brain perfusion pressure may underlie this effect up to a specific BP threshold [21]. This finding is consistent with our previously published observation that changes in brachial artery pulse pressure (PPR), SBP, and DBP differentially influenced hippocampal volumes depending on the cognitive phenotype and APOE genotypic categories [46].…”

Section: Discussionsupporting

confidence: 90%

Systolic Blood Pressure Is Associated with Increased Brain Amyloid Load in Mild Cognitively Impaired Participants: Alzheimer’s Disease Neuroimaging Initiatives Study

Fungwe¹,

Ngwa²,

Johnson³

et al. 2023

Dement Geriatr Cogn Disord

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Background: Cardiovascular disease (CVD), including elevated blood pressure (BP), is known to promote Alzheimer’s disease (AD) risk. Although brain amyloid load is a recognized hallmark of pre-symptomatic AD, its relationship to increased BP is less known. The objective of this study was to examine the relationship of BP to brain estimates of amyloid-β (Aβ) and standard uptake ratio (SUVr). We hypothesized that increased BP is associated with increased SUVr. Methods: Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we stratified BP according to the Seventh Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Classification (JNC VII). Florbetapir (AV-45) SUVr was derived from the averaged frontal, anterior cingulate, precuneus, and parietal cortex relative to the cerebellum. A linear mixed-effects model enabled the elucidation of amyloid SUVr relationships to BP. The model discounted the effects of demographics, biologics, and diagnosis at baseline within APOE genotype groups. The least squares means procedure was used to estimate the fixed-effect means. All analyses were performed using the Statistical Analysis System (SAS). Results: In non-ɛ4 carrier MCI subjects, escalating JNC categories of BP was associated with increasing mean SUVr using JNC-4 as a reference point (low-normal (JNC1) p = 0.018; normal (JNC-1) p = 0.039; JNC-2 p = 0.018 and JNC-3 p = 0.04). A significantly higher brain SUVr was associated with increasing BP despite adjustment for demographics and biological variables in non-ɛ4 carriers but not in ɛ4-carriers. This observation supports the view that CVD risk may promote increased brain amyloid load, and potentially, amyloid-mediated cognitive decline. Conclusion: Increasing levels of JNC classification of BP is dynamically associated with significant changes in brain amyloid burden in non-ɛ4 carriers but not in ɛ4-carrier MCI subjects. Though not statistically significant, amyloid burden tended to decrease with increasing BP in ɛ4 homozygote, perhaps motivated by increased vascular resistance and the need for higher brain perfusion pressure.

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Section: Discussionsupporting

confidence: 90%

Systolic Blood Pressure Is Associated with Increased Brain Amyloid Load in Mild Cognitively Impaired Participants: Alzheimer’s Disease Neuroimaging Initiatives Study

Fungwe¹,

Ngwa²,

Johnson³

et al. 2023

Dement Geriatr Cogn Disord

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“…Individuals with higher PP also had a higher incidence of conversion to AD. Taken together, these findings supported that PP elevation could increase risk of AD, and the associations maybe driven by amyloid plaques and subclinical neurodegeneration, which was consistent with the conclusion from previous studies that elevated PP had a negative impact on hallmark neuropathological markers of AD [ 8 , 12 , 13 , 18 ]. These likely suggested PP can be added to the current dementia risk models for dementia prevention, if controlled effectively, it would help delay the onset and reduce the number of demented people in the future.…”

Section: Discussionsupporting

confidence: 90%

“…The ADNI, an ongoing, multisite longitudinal, large-scale study launched in 2003, was designed to develop clinical, imaging, genetic and biochemical biomarkers for the early detection and tracking of AD [ 41 ]. Participants in the ADNI study underwent baseline and periodic physical and neurological examinations, standardized neuropsychological assessments, and biological sampling (blood, urine, and CSF) [ 13 ]. Regional ethical committees of all participating institutions approved the ADNI.…”

Section: Methodsmentioning

confidence: 99%

“…Others found arterial stiffness was associated with Aβ plaque deposition in the brain [ 15 ]. Furthermore, previous studies indicated arterial stiffness might play a role in early cognitive decline and brain atrophy in mid-to-late life [ 13 , 14 , 16 ]. However, these studies were mostly limited by their cross-sectional design and small samples, and the mechanisms underlying the association between PP and AD were still unclear.…”

Section: Introductionmentioning

confidence: 99%

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High pulse pressure is a risk factor for prodromal Alzheimer’s disease: a longitudinal study

Shi

Wang

Sun

et al. 2020

Aging

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It has been increasingly evident that pulse pressure (PP) is associated with Alzheimer's disease (AD) but whether PP increases AD risk and the mechanism responsible for this association remains unclear. To investigate the effects of PP in the process of AD, we have evaluated the cross-sectional and longitudinal associations of PP with AD biomarkers, brain structure and cognition and have assessed the effect of PP on AD risk in a large sample (n= 1,375) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Multiple linear regression and mixed-model regression were employed in cross-sectional and longitudinal analyses respectively. Clinical disease progression was assessed using Cox proportional hazards models. High PP was associated with lower β-amyloid 42 (Aβ 42 ) ( P = .015), and higher total tau (T-tau) ( P = .011), phosphorylated tau (P-tau) ( P = .003), T-tau/Aβ 42 ( P = .004) and P-tau/Aβ 42 ( P = .001), as well as heavier cortical amyloid-beta burden ( P = .011). Longitudinally, baseline high PP was significantly associated with hippocampal atrophy ( P = .039), entorhinal atrophy ( P = .031) and worse memory performance ( P = .058). Baseline high PP showed more rapid progression than those with normal PP ( P <.001). These results suggest PP elevation could increase AD risk, which may be driven by amyloid plaques and subclinical neurodegeneration.

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“…This data has been made available to investigators at institutions across the globe and has subsequently been interpreted and published in over 1000 studies since the inception of the initiative [3]. Such studies have explored potential early predictors of Alzheimer's disease, such as hypertension in middle-aged patients [4], cerebrospinal fluid changes correlated with age [5], and gender-specific factors [6].…”

Section: Introductionmentioning

confidence: 99%

Unsupervised Machine Learning to Identify Separable Clinical Alzheimer’s Disease Sub-Populations

et al. 2021

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Heterogeneity among Alzheimer’s disease (AD) patients confounds clinical trial patient selection and therapeutic efficacy evaluation. This work defines separable AD clinical sub-populations using unsupervised machine learning. Clustering (t-SNE followed by k-means) of patient features and association rule mining (ARM) was performed on the ADNIMERGE dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Patient sociodemographics, brain imaging, biomarkers, cognitive tests, and medication usage were included for analysis. Four AD clinical sub-populations were identified using between-cluster mean fold changes [cognitive performance, brain volume]: cluster-1 represented least severe disease [+17.3, +13.3]; cluster-0 [−4.6, +3.8] and cluster-3 [+10.8, −4.9] represented mid-severity sub-populations; cluster-2 represented most severe disease [−18.4, −8.4]. ARM assessed frequently occurring pharmacologic substances within the 4 sub-populations. No drug class was associated with the least severe AD (cluster-1), likely due to lesser antecedent disease. Anti-hyperlipidemia drugs associated with cluster-0 (mid-severity, higher volume). Interestingly, antioxidants vitamin C and E associated with cluster-3 (mid-severity, higher cognition). Anti-depressants like Zoloft associated with most severe disease (cluster-2). Vitamin D is protective for AD, but ARM identified significant underutilization across all AD sub-populations. Identification and feature characterization of four distinct AD sub-population “clusters” using standard clinical features enhances future clinical trial selection criteria and cross-study comparative analysis.

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Associations of Pulse and Blood Pressure with Hippocampal Volume by APOE and Cognitive Phenotype: The Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Cited by 8 publications

References 59 publications

Systolic Blood Pressure Is Associated with Increased Brain Amyloid Load in Mild Cognitively Impaired Participants: Alzheimer’s Disease Neuroimaging Initiatives Study

Systolic Blood Pressure Is Associated with Increased Brain Amyloid Load in Mild Cognitively Impaired Participants: Alzheimer’s Disease Neuroimaging Initiatives Study

High pulse pressure is a risk factor for prodromal Alzheimer’s disease: a longitudinal study

Unsupervised Machine Learning to Identify Separable Clinical Alzheimer’s Disease Sub-Populations

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