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Open Access 01.12.2022 | Research

Synergistic interaction of high blood pressure and cerebral beta-amyloid on tau pathology

verfasst von: Taewon Kim, Dahyun Yi, Min Soo Byun, Hyejin Ahn, Joon Hyung Jung, Nayeong Kong, Min Jung Kim, Gijung Jung, Jun-Young Lee, Yun-Sang Lee, Yu Kyeong Kim, Dong Young Lee, for the KBASE Research Group

Erschienen in: Alzheimer's Research & Therapy | Ausgabe 1/2022

Abstract

Background

Hypertension has been associated with Alzheimer’s disease (AD) dementia as well as vascular dementia. However, the underlying neuropathological changes that link hypertension to AD remain poorly understood. In our study, we examined the relationships of a history of hypertension and high current blood pressure (BP) with in vivo AD pathologies including β-amyloid (Aβ) and tau and also investigated whether a history of hypertension and current BP respectively affect the association between Aβ and tau deposition.

Methods

This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease, a prospective cohort study. Cognitively normal older adults who underwent both Aβ and tau positron emission tomography (PET) (i.e., [¹¹C]-Pittsburgh compound B and [¹⁸F] AV-1451 PET) were selected. History of hypertension and current BP were evaluated and cerebral Aβ and tau deposition measured by PET were used as main outcomes. Generalized linear regression models were used to estimate associations.

Results

A total of 68 cognitively normal older adults (mean [SD] age, 71.5 [7.4] years; 40 women [59%]) were included in the study. Neither a history of hypertension nor the current BP exhibited a direct association with Aβ or tau deposition. However, the synergistic interaction effects of high current systolic (β, 0.359; SE, 0.141; p = 0.014) and diastolic (β, 0.696; SE, 0.158; p < 0.001) BP state with Aβ deposition on tau deposition were significant, whereas there was no such effect for a history of hypertension (β, 0.186; SE, 0.152; p = 0.224).

Conclusions

The findings suggest that high current BP, but not a history of hypertension, synergistically modulate the relationship between cerebral Aβ and tau deposition in late-life. In terms of AD prevention, the results support the importance of strict BP control in cognitively normal older adults with hypertension.

Additional file 1: Supplementary Table 1. Interaction effect of global WMH volume and global Aβ on inferior tau deposition. Supplementary Table 2. Interaction effect of BP marker and global Aβ on inferior temporal tau deposition with additional adjustment with global WMH volume.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13195-022-01149-7.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Alzheimer’s disease

Blood pressure

Aβ

β-amyloid

PET

Positron emission tomography

CSF

Cerebrospinal fluid

SBP

Systolic blood pressure

Cognitively normal

KBASE

Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease

CERAD

Consortium to Establish a Registry for Alzheimer’s Disease

DBP

Diastolic blood pressure

VRS

Vascular risk score

PiB

Pittsburgh compound B

ROI

Region of interest

SUVR

Standardized uptake value ratio

Inferior temporal

GLM

Generalized linear regression model

APOE4

Apolipoprotein ε4

WMH

White matter hyperintensity

Background

Hypertension is related to a higher risk of dementia and more rapid cognitive decline in older adults [1‐5]. More specifically, hypertension is associated not only with the development of vascular dementia and vascular cognitive impairment [6‐8], but also with that of Alzheimer’s disease (AD) dementia [9‐11]. However, the underlying pathological changes that link hypertension to AD remain poorly understood.

While one postmortem study showed that midlife hypertension was associated with more senile plaque and neurofibrillary tangle pathologies at death [12], other studies reported that late-life high blood pressure (BP) was related only to neurofibrillary tangles or even to neither neurofibrillary tangles nor senile plaques [13, 14]. In vivo AD biomarker studies based on positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) analysis yielded similarly conflicting findings. Although a couple of studies demonstrated a significant association between high BP and cerebral β-amyloid (Aβ) deposition in older adults [15, 16], many other studies did not find such direct relationship [17‐24]. In terms of tau pathology, while a recent CSF study revealed that current BP had a significant positive association with tau level [17] and a PET study showed that systolic BP (SBP) synergistically interacted with Aβ on tau deposition [25], other studies reported that a history of hypertension was not related to CSF tau level or tau deposition on PET [19, 24]. As the current BP level reflects the appropriateness of hypertension management and a large proportion of hypertensive individuals exhibit poorly controlled BP, current BP status may explain the adverse effects of hypertension better than a history thereof [26‐28]. However, few studies have evaluated the effects of both a history of hypertension and current BP on AD pathologies in the same population.

In this context, we aimed to examine the relationships of a history of hypertension and current BP with in vivo AD pathologies (cerebral Aβ and tau deposition on PET) in cognitively normal (CN) older adults. We also investigated the modulatory effects of hypertension and current BP on the association between Aβ and tau deposition.

Methods

Participants

This study was performed as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study commenced in 2014. The KBASE study aimed to search for new AD biomarkers and investigate how different lifetime experiences and bodily changes contribute to the brain alterations related to AD [29]. The subject recruitment process was described previously [29]. Among the overall subjects of the KBASE cohort, 68 CN older adults (aged 55–90 years) who underwent both amyloid and tau PET imaging were included in the present study. All CN participants were free from diagnosis of mild cognitive impairment or dementia; they all had global Clinical Dementia Rating score of 0. The exclusion criteria were any serious medical, psychiatric, or neurological disorders that could affect mental functioning; history of loss of consciousness after head trauma; severe communication or behavioral problems that would make clinical examination or brain scans difficult; illiteracy; any significant visual or hearing difficulty; and participation in clinical trial with an investigational product. The study protocol was approved by the Institutional Review Boards of Seoul National University Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea. The study was performed in accordance with the recommendations of the current version of the Declaration of Helsinki. All participants provided written informed consent.

Clinical assessment

All participants were examined by neuropsychiatrists with advanced training in dementia research according to the KBASE clinical assessment protocol, which incorporates the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Assessment Packet [30]. A history of hypertension was defined as either a documented diagnosis of hypertension or treatment with antihypertensive medication, based on data collected by trained research nurses via interviews with participants and reliable informants. SBP and diastolic BP (DBP) were manually measured three times by a trained nurse at 5-min intervals in supine position after 5 min of rest. The mean SBP and DBP were used for the analysis. SBP and DBP were also categorized into high or low state using the following cutoffs: ≥ 140 vs. < 140 mmHg, and ≥ 90 vs. < 90 mmHg, respectively [31]. Comorbid vascular risk factors other than hypertension (diabetes mellitus, hyperlipidemia, coronary artery disease, transient ischemic attack, and stroke) were assessed in the same manner as the evaluation of hypertension history. A vascular risk score (VRS) reflecting the vascular burden other than hypertension was calculated based on the number of vascular risk factors other than hypertension [32].

Measurement of cerebral Aβ and tau deposition

All participants underwent three-dimensional [¹¹C]-Pittsburgh compound B (PiB)-PET using a 3.0 T Biograph mMR scanner (Siemens, Washington DC, USA) at the visit for clinical assessment including BP measurement. The details of PiB-PET image acquisition and preprocessing were described in our previous report [33]. The autonomic anatomical labeling algorithm and region combining method were used to set the regions of interest (ROIs) when characterizing the PiB retention in the frontal, lateral parietal, posterior cingulate-precuneus, and lateral temporal cortices [34, 35]. The standardized uptake value ratio (SUVR) for each ROI was calculated by dividing each value by the mean cerebellar uptake value in the same image. A global cortical ROI comprising the four ROIs was also defined, and a global Aβ retention value was generated by dividing the mean value for all voxels of the global cortical ROI by the mean cerebellar uptake value in the same image.

Participants also underwent [¹⁸F] AV-1451 PET scans using a Biograph True point 40 PET/CT scanner (Siemens, USA) per the manufacturer’s approved guidelines. While PiB-PET was performed during the baseline visit, AV-1451 PET imaging was performed at an average of 72 days after the baseline visit. The details of AV-1451 PET image acquisition and preprocessing were described in our previous report [33]. AV-1451 PET SUVR images based on the mean uptake over 80 to 100 min post-injection were normalized by the mean inferior cerebellar gray matter uptake, according to the published code [36]. To estimate cerebral tau deposition, we quantified the partial volume-corrected AV-1451 SUVR of inferior temporal (IT) ROI, which is the neocortical site of tau deposition in early AD [37, 38].

Statistical analysis

For demographic and clinical characteristics, comparisons between participants with and without a history of hypertension were performed using the χ² test or Fisher’s exact test for categorical data, and the independent t-test for continuous data. We used generalized linear regression model (GLM) to determine whether global Aβ and IT tau deposition were directly associated with a history of hypertension and high current BP (SBP and DBP; using both categorical and continuous variable) after adjusting for age, sex, apolipoprotein ε4 (APOE4) positivity, and the VRS. To analyze the moderating effect of a history of hypertension and current BP on the association between Aβ on tau deposition, a similar GLM including an interaction term of history of hypertension (or current SBP or DBP) × global Aβ retention as an additional independent variable was used. All statistical analyses utilized SPSS software (version 22.0, SPSS Inc; Chicago, IL, USA), and two-tailed p-values < 0.05 were considered statistically significant.

Results

Participant characteristics

A total of 68 participants (mean [SD] age, 71.5 [7.4] years; 40 women [59%]) were included in the study. Their demographic and clinical characteristics are summarized in Table 1. Of the 34 participants with a history of hypertension, 32 (94%) were on antihypertensive medication. Participants with a history of hypertension had higher VRS than the others, but there was no difference in age, sex, education, APOE4 positivity, SBP, or DBP between the two groups.

Table 1

Demographic and clinical characteristics of participants

Characteristics	History of hypertension (n = 34)	No history of hypertension (n = 34)	p-value
Age in years, mean (SD)	72.2 (8.0)	70.7 (6.7)	0.425
Females, (%)	21 (62)	19 (56)	0.622
Education in years, mean (SD)	12.1 (4.2)	11.9 (4.0)	0.906
APOE4 carrier, (%)	7 (21)	5 (15)	0.525
SBP in mmHg, mean (SD)	128.8 (14.9)	124.3 (19.4)	0.281
DBP in mmHg, mean (SD)	78.1 (10.2)	75.0 (11.9)	0.253
Onset age of hypertension in years, mean (SD)	60.6 (8.6)	-
Duration of hypertension in years, mean (SD)	11.6 (7.0)	-
Treatment with antihypertensive medication, (%)	32 (94)	-
Diabetes mellitus, (%)	12 (35)	8 (24)	0.287
Coronary artery disease^a, (%)	4 (12)	1 (3)	0.356
Dyslipidemia, (%)	17 (50)	12 (35)	0.220
Stroke, (%)	1 (3)	0
TIA	0	0
VRS, mean (SD)	1.00 (0.78)	0.62 (0.78)	0.047
Global WMH volume in mL, mean (SD)	17.53 (15.04)	12.00 (13.00)	0.108

Abbreviations: APOE4 apolipoprotein E ε4, SBP systolic blood pressure, DBP diastolic blood pressure, TIA transient ischemic attack, VRS vascular risk score, WMH white matter hyperintensity

^a Fisher’s exact test was used for data comparison; other categorical characteristics were compared using the chi-square test and the continuous characteristics were compared using the independent t-test

Relationships of a history of hypertension and current BP with in vivo AD pathologies

Neither global Aβ nor IT tau deposition was significantly different according to history of hypertension and high current SBP or DBP state (categorical variable), although IT tau deposition was marginally greater in high- than low-DBP group (Tables 2 and 3; Fig. 1). Current SBP or DBP (continuous variable) also exhibited no significant associations with Aβ and tau deposition (Table 4).

Table 2

Cerebral Aβ and tau deposition in participants with and without a history of hypertension

Variables	History of hypertension (n = 34)	No history of hypertension (n = 34)	Regression results^a
Variables	History of hypertension (n = 34)	No history of hypertension (n = 34)	β (SE)	p-value
Global Aβ deposition, mean (SD)	1.367 (0.400)	1.354 (0.407)	−0.001 (0.094)	0.989
IT tau deposition, mean (SD)	1.438 (0.308)	1.411 (0.238)	0.030 (0.068)	0.654

Abbreviations: Aβ β-amyloid, IT inferior temporal, SE standard error

^a Each linear regression model for global Aβ or IT tau deposition included a history of hypertension as an independent variable, after adjusting for age, sex, apolipoprotein E ε4 positivity, and the vascular risk score

Table 3

Cerebral Aβ and tau deposition in participants with and without high current blood pressure

Variables	High current SBP (n = 22)	Low current SBP (n = 46)	Regression results^a
Variables	High current SBP (n = 22)	Low current SBP (n = 46)	β (SE)	p-value
Global Aβ deposition, mean (SD)	1.354 (0.483)	1.364 (0.360)	−0.079 (0.099)	0.426
IT tau deposition, mean (SD)	1.449 (0.377)	1.413 (0.210)	0.001 (0.072)	0.984
Variables	High current DBP (n = 12)	Low current DBP (n = 56)	Regression results^a
Variables	High current DBP (n = 12)	Low current DBP (n = 56)	β (SE)	p-value
Global Aβ deposition, mean (SD)	1.354 (0.483)	1.364 (0.360)	−0.153 (0.120)	0.206
IT tau deposition, mean (SD)	1.449 (0.377)	1.413 (0.210)	0.158 (0.085)	0.070

Abbreviations: Aβ β-amyloid, IT inferior temporal, SBP systolic blood pressure, DBP diastolic blood pressure, SE standard error

^a Each linear regression model for global Aβ or IT tau deposition included high current SBP (≥ 140 mmHg) or DBP state (≥ 90 mmHg) as a categorical independent variable, after adjusting for age, sex, apolipoprotein E ε4 positivity, and the vascular risk score

Table 4

Associations of current systolic and diastolic blood pressure level with cerebral Aβ and tau deposition

Variables^a	β (SE)	p-value
SBP (continuous)
Global Aβ	−0.003 (0.003)	0.280
IT tau	0.000 (0.002)	0.973
DBP (continuous)
Global Aβ	−0.008 (0.004)	0.082
IT tau	0.002 (0.003)	0.511

Abbreviations: Aβ β-amyloid, SBP systolic blood pressure, IT inferior temporal, DBP diastolic blood pressure, SE standard error

^a Each linear regression model for global Aβ or IT tau deposition included SBP or DBP level as a continuous independent variable, after adjusting for age, sex, apolipoprotein E ε4 positivity, and the vascular risk score

Interaction effect between a history of hypertension (or current BP) and Aβ deposition on tau deposition

The interaction effect of a history of hypertension with global Aβ deposition on IT tau deposition was not significant (β, 0.186; SE, 0.152; p = 0.224) (Table 5 and Fig. 2A). In contrast, significant synergistic interaction effects of high current SBP and DBP states (categorical variables) with global Aβ on IT tau deposition were observed (β, 0.359; SE, 0.141; p = 0.014; β, 0.696; SE, 0.158; p < 0.001, respectively) (Table 5, Fig. 2B and C). Similarly, current SBP and DBP (continuous variables) also showed significant synergistic interactions (β, 0.011; SE, 0.004; p = 0.005; β, 0.019; SE, 0.006; p = 0.002, respectively) with global Aβ deposition on IT tau deposition (Table 5). As shown in Fig. 2B and C, the relationship between Aβ and tau deposition was stronger in individuals with high SBP (or DBP) than those with low SBP (or DBP).

Table 5

Interaction effects of history of hypertension or current blood pressure with global Aβ on inferior temporal tau deposition

	β (SE)	p-value
IT tau ~ BP marker × global Aβ + BP marker + global Aβ + age + sex + APOE4 + VRS^a
History of hypertension × global Aβ	0.186 (0.152)	0.224
High current SBP state × global Aβ	0.359 (0.141)	0.014
High current DBP state × global Aβ	0.696 (0.158)	< 0.001
Current SBP (continuous) × global Aβ	0.011 (0.004)	0.005
Current DBP (continuous) × global Aβ	0.019 (0.006)	0.002

Abbreviations: Aβ β-amyloid, BP blood pressure, APOE4 apolipoprotein E ε4 positivity, VRS vascular risk score, SBP systolic blood pressure, DBP diastolic blood pressure, SE standard error

^a Summary of generalized linear regression model, repeated for each blood pressure marker (e.g., history of hypertension, high current blood pressure state, or current blood pressure level) and global Aβ as interactive predictors of tau deposition

Discussion

In the current study, neither a history of hypertension nor the current BP was directly associated with Aβ or tau deposition (Tables 2 and 3; Fig. 1). However, the synergistic interaction effect of current BP with Aβ on tau deposition was significant, whereas the interaction effect between a history of hypertension and Aβ was not (Table 5 and Fig. 2). Our finding of no direct association of hypertension history or current BP with Aβ deposition is in line with many previous in vivo AD biomarker studies [17‐24], although one postmortem study reported a positive association between BP measured in midlife and senile plaque pathology at death [12] and a biomarker study reported a positive relationship between BP and Aβ deposition in late middle-aged adults [15]. Taken together, although we cannot exclude the possibility that high BP in midlife may influence cerebral Aβ accumulation, high current BP or history of hypertension in late-life does not seem to be directly related to an increased Aβ burden.

We found no significant direct association of current BP or hypertension history with cortical tau deposition as well, which is comparable to the results in previous CSF and PET studies [18, 19, 24]. In contrast to these findings, a recent Chinese study reported a significant association of hypertension history and higher SBP with greater CSF tau level in individuals aged between 40 and 90 years [17]. However, its subgroup analyses revealed that association was significant only for the younger subgroup (< 65 years of age), but not for the older subgroup (≥ 65 years of age), of which the age distribution and result are similar to those of our study.

While we found no direct association between current BP and tau deposition, there was a significant synergistic interaction effect of current SBP and DBP with Aβ on tau deposition. The relationship between Aβ and tau deposition was greater in individuals with high SBP (or DBP) than in those with low SBP (or DBP), suggesting that current (late-life) BP moderates the relationship between cerebral Aβ and tau. Similarly, a synergistic interaction of SBP and cerebral Aβ burden on cortical tau deposition was recently reported, although the effect of DBP was not investigated [25]. It is difficult to determine the exact mechanism by which high BP acts in AD pathobiology. However, decreased cerebral blood flow and damaged blood-brain barrier, both of which can be caused by high BP, might be the contributing factors since both of them interact with Aβ to increase tau deposition [39]. Tau pathology may be exacerbated by increased tau hyperphosphorylation associated with chronic cerebral hypoperfusion and reduced tau clearance related with impairment of blood-brain barrier and glymphatic system [40‐42]. Additionally, given that tau pathology is related to the missorting of axonal tau into somatodendritic compartment by Aβ deposition and other neuronal insults [43], we assessed the potential mediation of cerebrovascular insult, measured by white matter hyperintensities (WMHs), for the synergistic interaction effect of current BP with Aβ on tau deposition. We first analyzed the interaction effect of global WMH volume (instead of a history of hypertension or current BP) with global Aβ on tau deposition. As shown in Additional file 1: Supplementary Table 1, the interaction effect was not significant. Furthermore, the results presented in Table 5 were largely unchanged even when we controlled global WMH volume as an additional covariate (See Additional file 1: Supplementary Table 2). These findings indicate that cerebrovascular injury measured by WMHs does not mediate the synergistic effect of high BP on tau pathology.

In contrast to high current BP, the interaction effect of a history of hypertension with Aβ on tau deposition was not significant. This may support the importance of strict BP monitoring and control in individuals with hypertension in order to prevent AD-related cognitive decline. Multiple studies reported that individuals with untreated hypertension or less intensive BP control were at higher risk of cognitive decline [44‐46]. In the present study, most (32/34, 94%) participants with a history of hypertension were on antihypertensive medication. However, 14 (44%) of them still had high current SBP or DBP, i.e., poorly controlled hypertension.

A novel point of this study is that we specifically identified that high SBP and DBP in late-life, but not a history of hypertension, synergistically interact with in vivo cerebral amyloid deposition on tau accumulation. However, several limitations should be considered. First, as the study was cross-sectional, we could not infer causality in the relationship between high BP and AD pathology. In addition, long-term BP variability may be a more important factor than BP at single point [47]. Further longitudinal studies with larger sample size and sufficient long-term BP variability data are required. Second, the participants had relatively narrow ranges of BP (SBP, 80 mmHg to 160 mmHg; DBP, 50 mmHg to 100 mmHg). Even in the group with a history of hypertension, most individuals (32/34, 94%) were on anti-hypertensive medication and only a few had very high BP (three with SBP ≥ 160 mmHg and three with DBP ≥ 100 mmHg). This might have reduced the likelihood of detecting any direct association between very high BP and in vivo AD pathology. Third, we did not consider the effect of specific details for antihypertensive medication history, such as onset, duration, and dosage of the medication, and specific drug(s) administered, although such details may affect the association between hypertension history and AD biomarkers. Finally, the impact of cerebral blood flow alteration, caused by hypertension, on PET radioligand binding dynamics needs to be considered when interpreting the results. High BP reduces cerebral blood flow, which can potentially decrease estimates of PET ligand binding (i.e., estimates of Aβ or tau deposition) in the brain [48, 49]. However, given that high BP, synergistically with Aβ, increased cerebral tau deposition rather than decreased it, it is not likely that the influence of cerebral blood flow on estimates of PET ligand binding was a major determinant of our results.

Conclusion

Our findings suggest that high current BP, rather than a history of hypertension, may synergistically modulate the relationship between cerebral Aβ burden and tau deposition in later life. In terms of AD prevention, our results support the importance of strict BP control in cognitively normal older adults with hypertension.

Acknowledgements

We thank all the members of the KBASE Research Group for their contribution. A complete list of KBASE research group members can be found at http://kbase.kr/. We sincerely appreciate the time and effort of all the participants in the research.

Declarations

The study protocol was approved by the Institutional Review Boards of Seoul National University Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea. All participants provided written informed consent.

Not applicable

Competing interests

The authors declare that they have no competing interests.

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Supplementary Information

Kilander L, Nyman H, Boberg M, Hansson L, Lithell H. Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men. Hypertension. 1998;31(3):780–6.CrossRef

Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ. The association between midlife blood pressure levels and late-life cognitive function. The Honolulu-Asia Aging Study. JAMA. 1995;274(23):1846–51.CrossRef

Elias MF, Elias PK, Sullivan LM, Wolf PA, D'Agostino RB. Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study. Int J Obes Relat Metab Disord. 2003;27(2):260–8.CrossRef

Waldstein SR, Giggey PP, Thayer JF, Zonderman AB. Nonlinear relations of blood pressure to cognitive function: the Baltimore Longitudinal Study of Aging. Hypertension. 2005;45(3):374–9.CrossRef

Köhler S, Baars MA, Spauwen P, Schievink S, Verhey FR, van Boxtel MJ. Temporal evolution of cognitive changes in incident hypertension: prospective cohort study across the adult age span. Hypertension. 2014;63(2):245–51.CrossRef

Sharp SI, Aarsland D, Day S, Sønnesyn H, Ballard C, Group AsSVDSR. Hypertension is a potential risk factor for vascular dementia: systematic review. Int J Geriatr Psychiatry. 2011;26(7):661–9.CrossRef

Muller M, Sigurdsson S, Kjartansson O, Aspelund T, Lopez OL, Jonnson PV, et al. Joint effect of mid- and late-life blood pressure on the brain: the AGES-Reykjavik study. Neurology. 2014;82(24):2187–95.CrossRef

van Dijk EJ, Prins ND, Vrooman HA, Hofman A, Koudstaal PJ, Breteler MM. Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study. Stroke. 2008;39(10):2712–9.CrossRef

Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, et al. Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med. 2002;137(3):149–55.CrossRef

10.

Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R. Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology. 2005;65(4):545–51.CrossRef

11.

Lennon MJ, Makkar SR, Crawford JD, Sachdev PS. Midlife Hypertension and Alzheimer's Disease: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2019;71(1):307–16.CrossRef

12.

Petrovitch H, White LR, Izmirilian G, Ross GW, Havlik RJ, Markesbery W, et al. Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Honolulu-Asia aging Study. Neurobiol Aging. 2000;21(1):57–62.CrossRef

13.

Arvanitakis Z, Capuano AW, Lamar M, Shah RC, Barnes LL, Bennett DA, et al. Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology. 2018;91(6):e517–e25.CrossRef

14.

Wang LY, Larson EB, Sonnen JA, Shofer JB, McCormick W, Bowen JD, et al. Blood pressure and brain injury in older adults: findings from a community-based autopsy study. J Am Geriatr Soc. 2009;57(11):1975–81.CrossRef

15.

Langbaum JB, Chen K, Launer LJ, Fleisher AS, Lee W, Liu X, et al. Blood pressure is associated with higher brain amyloid burden and lower glucose metabolism in healthy late middle-age persons. Neurobiol Aging. 2012;33(4):827 e11-9.CrossRef

16.

Toledo JB, Toledo E, Weiner MW, Jack CR Jr, Jagust W, Lee VM, et al. Cardiovascular risk factors, cortisol, and amyloid-beta deposition in Alzheimer's Disease Neuroimaging Initiative. Alzheimers Dement. 2012;8(6):483–9.CrossRef

17.

Hu H, Meng L, Bi YL, Zhang W, Xu W, Shen XN, et al. Tau pathologies mediate the association of blood pressure with cognitive impairment in adults without dementia: The CABLE study. Alzheimers Dement. 2022;18(1):53–64.CrossRef

18.

Glodzik L, Mosconi L, Tsui W, de Santi S, Zinkowski R, Pirraglia E, et al. Alzheimer's disease markers, hypertension, and gray matter damage in normal elderly. Neurobiol Aging. 2012;33(7):1215–27.CrossRef

19.

Kester MI, van der Flier WM, Mandic G, Blankenstein MA, Scheltens P, Muller M. Joint effect of hypertension and APOE genotype on CSF biomarkers for Alzheimer's disease. J Alzheimers Dis. 2010;20(4):1083–90.CrossRef

20.

Gottesman RF, Schneider AL, Zhou Y, Coresh J, Green E, Gupta N, et al. Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition. JAMA. 2017;317(14):1443–50.CrossRef

21.

Vemuri P, Knopman DS, Lesnick TG, Przybelski SA, Mielke MM, Graff-Radford J, et al. Evaluation of Amyloid Protective Factors and Alzheimer Disease Neurodegeneration Protective Factors in Elderly Individuals. JAMA Neurol. 2017;74(6):718–26.CrossRef

22.

Rodrigue KM, Rieck JR, Kennedy KM, Devous MD Sr, Diaz-Arrastia R, Park DC. Risk factors for beta-amyloid deposition in healthy aging: vascular and genetic effects. JAMA Neurol. 2013;70(5):600–6.CrossRef

23.

Lane CA, Barnes J, Nicholas JM, Sudre CH, Cash DM, Parker TD, et al. Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study. Lancet Neurol. 2019;18(10):942–52.CrossRef

24.

Vemuri P, Lesnick TG, Przybelski SA, Knopman DS, Lowe VJ, Graff-Radford J, et al. Age, vascular health, and Alzheimer disease biomarkers in an elderly sample. Ann Neurol. 2017;82(5):706–18.CrossRef

25.

Rabin JS, Yang HS, Schultz AP, Hanseeuw BJ, Hedden T, Viswanathan A, et al. Vascular Risk and beta-Amyloid Are Synergistically Associated with Cortical Tau. Ann Neurol. 2019;85(2):272–9.CrossRef

26.

Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16(4):223–37.CrossRef

27.

Waldstein SR, Brown JR, Maier KJ, Katzel LI. Diagnosis of hypertension and high blood pressure levels negatively affect cognitive function in older adults. Ann Behav Med. 2005;29(3):174–80.CrossRef

28.

Kjeldsen SE, Narkiewicz K, Burnier M, Oparil S. Intensive blood pressure lowering prevents mild cognitive impairment and possible dementia and slows development of white matter lesions in brain: the SPRINT Memory and Cognition IN Decreased Hypertension (SPRINT MIND) study. Blood Press. 2018;27(5):247–8.CrossRef

29.

Byun MS, Yi D, Lee JH, Choe YM, Sohn BK, Lee JY, et al. Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease: Methodology and Baseline Sample Characteristics. Psychiatry Investig. 2017;14(6):851–63.CrossRef

30.

Lee JH, Lee KU, Lee DY, Kim KW, Jhoo JH, Kim JH, et al. Development of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K): clinical and neuropsychological assessment batteries. J Gerontol B Psychol Sci Soc Sci. 2002;57(1):P47–53.CrossRef

31.

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206–52.CrossRef

32.

DeCarli C, Mungas D, Harvey D, Reed B, Weiner M, Chui H, et al. Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia. Neurology. 2004;63(2):220–7.CrossRef

33.

Park JC, Han SH, Yi D, Byun MS, Lee JH, Jang S, et al. Plasma tau/amyloid-beta1-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer's disease. Brain. 2019;142(3):771–86.CrossRef

34.

Rolls ET, Joliot M, Tzourio-Mazoyer N. Implementation of a new parcellation of the orbitofrontal cortex in the automated anatomical labeling atlas. Neuroimage. 2015;122:1–5.CrossRef

35.

Reiman EM, Chen K, Liu X, Bandy D, Yu M, Lee W, et al. Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease. Proc Natl Acad Sci U S A. 2009;106(16):6820–5.CrossRef

36.

Baker SL, Maass A, Jagust WJ. Considerations and code for partial volume correcting [(18)F]-AV-1451 tau PET data. Data Brief. 2017;15:648–57.CrossRef

37.

Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112(4):389–404.CrossRef

38.

Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J, Rentz D, et al. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol. 2016;79(1):110–9.CrossRef

39.

Albrecht D, Isenberg AL, Stradford J, Monreal T, Sagare A, Pachicano M, et al. Associations between Vascular Function and Tau PET Are Associated with Global Cognition and Amyloid. J Neurosci. 2020;40(44):8573–86.CrossRef

40.

Zhao Y, Gong CX. From chronic cerebral hypoperfusion to Alzheimer-like brain pathology and neurodegeneration. Cell Mol Neurobiol. 2015;35(1):101–10.CrossRef

41.

Mortensen KN, Sanggaard S, Mestre H, Lee H, Kostrikov S, Xavier ALR, et al. Impaired Glymphatic Transport in Spontaneously Hypertensive Rats. J Neurosci. 2019;39(32):6365–77.CrossRef

42.

Michalicova A, Majerova P, Kovac A. Tau Protein and Its Role in Blood-Brain Barrier Dysfunction. Front Mol Neurosci. 2020;13:570045.CrossRef

43.

Zempel H, Mandelkow E. Lost after translation: missorting of Tau protein and consequences for Alzheimer disease. Trends Neurosci. 2014;37(12):721–32.CrossRef

44.

Gao S, Jin Y, Unverzagt FW, Liang C, Hall KS, Ma F, et al. Hypertension and cognitive decline in rural elderly Chinese. J Am Geriatr Soc. 2009;57(6):1051–7.CrossRef

45.

Turana Y, Tengkawan J, Chia YC, Hoshide S, Shin J, Chen CH, et al. Hypertension and Dementia: A comprehensive review from the HOPE Asia Network. J Clin Hypertens (Greenwich). 2019;21(8):1091–8.CrossRef

46.

Group SMIftSR, Williamson JD, Pajewski NM, Auchus AP, Bryan RN, Chelune G, et al. Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA. 2019;321(6):553–61.CrossRef

47.

Sible IJ, Nation DA. Alzheimer's Disease Neuroimaging I. Visit-to-Visit Blood Pressure Variability and CSF Alzheimer Disease Biomarkers in Cognitively Unimpaired and Mildly Impaired Older Adults. Neurology. 2022;98(24):e2446–e53.CrossRef

48.

Muller M, van der Graaf Y, Visseren FL, Mali WP, Geerlings MI, Group SS. Hypertension and longitudinal changes in cerebral blood flow: the SMART-MR study. Ann Neurol. 2012;71(6):825–33.CrossRef

49.

Cselenyi Z, Farde L. Quantification of blood flow-dependent component in estimates of beta-amyloid load obtained using quasi-steady-state standardized uptake value ratio. J Cereb Blood Flow Metab. 2015;35(9):1485–93.CrossRef

Titel: Synergistic interaction of high blood pressure and cerebral beta-amyloid on tau pathology
verfasst von: Taewon Kim
Dahyun Yi
Min Soo Byun
Hyejin Ahn
Joon Hyung Jung
Nayeong Kong
Min Jung Kim
Gijung Jung
Jun-Young Lee
Yun-Sang Lee
Yu Kyeong Kim
Dong Young Lee
for the KBASE Research Group
Publikationsdatum: 01.12.2022
Verlag: BioMed Central
Erschienen in: Alzheimer's Research & Therapy / Ausgabe 1/2022
Elektronische ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-022-01149-7

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Abstract

Background

Methods

Results

Conclusions

Supplementary Information

Publisher’s Note

Background

Methods

Participants

Clinical assessment

Measurement of cerebral Aβ and tau deposition

Statistical analysis

Results

Participant characteristics

Relationships of a history of hypertension and current BP with in vivo AD pathologies

Interaction effect between a history of hypertension (or current BP) and Aβ deposition on tau deposition

Discussion

Conclusion

Acknowledgements

Declarations

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Supplementary Information

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