Table 1 Summary

#

Author

Study name, country

Study design

Follow-up, years

Population

Sample size, n

Gender, race, %

Age, years

Hypertension

[HTN, % HTNM, %, SBP, mmHg]

Arterial stiffness

Cognition:

Neuroimaging, Neuropsychological tests

Conclusion

1

Hajjar I. et al., 2016

Emory University, USA

Cohort longitudinal

4y

Employees of Emory University

591

68%F

70%W

24%B

48.8

83%

cfPWV (7.2)

MDR

Memory recognition

VSL

SSTM

Pattern recall

DPR

Recognition of pattern

EFT

MF

DSST

FBDS

Symbol spotting

FSA

1. HTN + increased PWV were associated with a decline in executive score

2. In healthy adults increased cfPWV was superior to BP in predicting cognitive decline in all domains

3. The treatment of arterial stiffness in hypertensives is crucial for cognitive health prevention

2

Pase M.P. et al., 2016

FHS

 (Framingham Heart Study), US

Population-based observational cohort

since 1948

FHS G3 and offspring cohort

1101

54%F

69±6

58%

43% HTNM

cfPWV (10.6)

DSMMD – Dementia (7%)

NINCDSAD – AD (5%) Petersen criteria – MCI (10%)

1. cfPWV predicts MCI in total sample, dementia and AD in non-diabetics.

2. Brachial PP is associated with increased risk of dementia

3

Nilsson E.D. et al., 2014

MDCS

(Malmo Diet and Cancer Study), Sweden

Population-based prospective cohort,

cross-sectional analysis

1991-start

5y

Sweden population

2637

60.8%F

72.1±5.6

135.6/75.6mmHg

47.7% HTNM

cfPWV (10.5±2.5)

AQT MMSE

1.Increased cfPWV was inversely associated with cognition

2. There is a linear association between cfPWV and cognitive speed after adjusting for cardiovascular risk factors

4

Nilsson E.D. et al., 2017

MDCS

(Malmo Diet and Cancer Study), Sweden

Population-based prospective cohort

1991-start

5y

Sweden population

3056

43.1%M

61-85

137.8/74.6mmHg

60.8% HTNM

cfPWV (10.5±2.4)

MMSE, AQT-color form DSSMD

1. Higher cfPWV is associated with dementia, before adjustment

2. No association between cfPWV and all-cause dementia and AD after adjustment to vascular factors

5

Watson N.L. et al., 2011

Health ABC Study, Cognitive Validity Substudy

(Aging and Body Composition Study), US

Prospective cohort

1997-enroll

9y

Pittsburg, PA; Memphis, TNMedicare

552

48%M

42%B

73.1±2.7

50%

cfPWV (8.9±3.9)

3MSE

Central AS contributes to cognitive decline independent of HTN and vascular risk factors

6

Menezes S.T. et al., 2019

ELSA-Brazil, (Brazilian Longitudinal Study of Adult Health)

Longitudinal multicenter cohort

3.8y

6 Brazilian cities

6927

55%F

58.8±5.9

(baseline)

62.7±5.9 (follow-up)

SBP 130.2±18.9

39.4% HTNM

cfPWV (9.9±1.9)

Memory test scoreVFTTrial-B

1. Increased cfPWV was associated with a sharper decline in cognitive performances, regardless of SBP among younger group.

2. Decline in cognition was faster among older cohorts

7

Araghi M. et al., 2020

Whitehall II, UK

Longitudinal cohort

Start in 1985

7y 

London-based British civil servant

4300

25.3%F

92.3%W

65.3±5.7

124.5/70.7mmHg

32.7% HTNM

cfPWV

(3 groups:

<7.41; 7.41-8.91; >8.91)

AH4-I

global, memory, phonemic and semantic fluency

MMSE

1. Higher cfPWV was associated with faster cognitive decline

2. The highest third of PWV had the highest rate of HTN (41.6%)

8

Cooper L et al., 2016

AGES-Reykjavik (Age, Gene/Environmental Susceptibility Study), Iceland

Cohort prospective, cross-sectional analysis

5y

Iceland population

1820

60%F

80±5

144/64mmHg

71% HTNM

cfPWV (13.6±4.6)

MRI

CVLT

DSST

Stroop test

EFT

WMH 15%

Microbleeds 29%

In older adults, cardiovascular resistance and WMH are associated with higher cfPWV and lower memory scores. MAP and segmental brain volumes were associated with cfPWV and memory scores, but not both measures

9

Mitchell G.F., et al., 2011

AGES-Reykjavik Study

(Age, Gene/Environmental Susceptibility Study), Iceland

Community-based prospective

1967 -start

4y

Iceland population

668

57%F

75±4F

76±4M

63%F

54%M

Carotid PP*

AI

Pix*

cfPWV*

(F 12.2±3.7

M 13.4±4.4)

icfPWV

MRI

MMSE

GDS score

1. Increased cfPWV and Pix were associated with higher volume of WMH, subcortical infarcts and reduced cognitive function

2. Stiff aorta was associated with lower wave reflection and lower cognitive scores

3. The higher level of BP and cfPWV are associated with diffuse brain damage and lower cognitive scores

10

RibaLlena I., et al., 2018

ISSYS (Investigating Silent Strokes in Hypertensives), Spain

Community-based prospective ongoing

3y

Hypertensive Spanish population

782

49.6%F

62.7±5.4

142.9/77.3mmHg

95.3% HTNM

cfPWV

(9.2-11.9)

MRI

7.2% -Lacunes

6.4% - microbleeds

6.7% WMH

24.5% EPVS in basal ganglia

40.1% EPVS in the centrum semiovale

In hypertensive population cfPWV is associated with total load of CSVD, especially EPVS

11

Maillard P., et al., 2017

FHS

 (Framingham Heart Study), US

Population-based observational cohort

Since 1948

FHS G3 and offspring cohort

2422

45.91%M

51.3±11.6

SBP 122.73±17.37mmHg

36.86% HTNM

cfPWV (7.9)

MRI DTI

1. cfPWV is associated with higher FW, FA, WMH

2. the effect of SBP on FW is mediated by cfPWV

12

Benetos A. et al., 2012

PARTAGE

(Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized and Very Aged Population), France

Longitudinal multicenter prospective

3 year

Nursing home

873

79%F

87±5

73%

95% HTNM

cfPWV (14.4 ±5)

MMSE

Katz ADL

1. The higher cfPWV, the more profound the cognitive decline

2. PWV but not BP is associated with cognitive decline

13

Collin C. et al., 2010

3 City Dijon study, France

Ongoing population-based longitudinal study, cross-sectional analysis

Start in 1991

6 follow-ups over 10y

Bordeaux, Dijon, Montpellier

931

37.5%M

75±3.7

69.3%

cfPWV

(m 15.2±3.3

f 14.3+3.1)

WMLV

1. In females the higher SBP was significantly associated with larger total WMLV

2. In males AS was significantly associated with higher periventricular WMLV after adjustment to MAP

14

Kim E.D. et al., 2017

PACE

(Predictors of Arrhythmic and Cardiovascular Risk in ESRD), US

Prospective population-based

1y

Outpatient dialysis units in Baltimore

568

58%M72%B

55±13

100%

cfPWV (10.0)

AI

cPP

TMT A, B

3MSE

Cognitive impairment 10%

1. Higher cfPWV and cPP were associated with TMT A, B, but association was attenuated after multivariable adjustment. 2. Higher AI and cPP were associated with cognitive decline in end-stage renal disease patients, but not cfPWV

15

Amier R.P., et al., 2021

HBCS

(Heart-Brain Connection Study), Netherlands

Multicenter prospective observational, cross-sectional analysis

09/2014-12/2017

3y3m

4 University medical center

559

35.8%F

67.8±8.8

56.8%

aoPWV (8.4) (MRI)

Dutch Parelsnoer Initiative (memory, language, speed, executive function MRI

1. Higher aoPWV, LVMi, and LVMVR were associated with the extent CSVD and cognitive impairment only in patients with cardiovascular diseases

2. The worse brain damage is correlated to SBP or HTN

3. Severity and duration of HTN are related to higher CSVD and cognitive impairment

16

Taniguchi Y. et al., 2015

Health examination, Japan

Longitudinal prospective population-based

Start 2008

3.4y

Community-dwelling older Japanese

526

57.8%F

71.7±5.6

36.3%

33.5% HTNM

baPWV (17.82)

MMSE >26 points (94.1%)

Cognitive decline 16.2%

baPWV is independently associated with cognitive decline after adjustment for BP and HTN med

17

Han F. et al., 2021

Ongoing population based Shunyi cohort study, China

Cross-sectional analysis

3y

Suburb district of Beijing

933

63.7%F

55.5±9.1

49.8%

baPWV (15.7±3.2)

MMSE (26.4)

MRI DTI

Dementia 26%

1. baPWV is independently associated with white matter deterioration, decreased FA, increased mean, axial, radial diffusivity

2. General cognitive function worsened with increased baPWV after adjusting for hypertension

18

Palta P., et al., 2019

ARIC-NCS

(Atherosclerosis Risk in Communities-Neurocognitive Study), US

Community-based prospective

1987- start

2y

Washington County, MD; Forsyth County, NC; Minneapolis, MN; Jakson, MS

3703

60%F

20.8%B

75.2

(67-90)

63.5%

cfPWV

cPP

MRI

DWR

DSST

TMT A, B

BNT

1. The higher cfPWV, the greater WMH, the lower cognitive scores

2. cPP was associated with brain damage and poorer cognitive performance

3. cfPWV and PP has the strongest association with executive function and speed

4. No significant interaction by hypertension is observed.

19

Meyer M. L. et al., 2017

ARIC-NCS

(Atherosclerosis Risk in Communities-Neurocognitive Study), US

Cross-sectional analysis

Over 25y

Washington County, MD; Forsyth County, NC; Minneapolis, MN; Jakson, MS

6538

4461 (for visit 5)

58.8%F

70-89y

Mean 75.4±5y

20.4%B

71.8%

72.4%

cfPWV (11.54-13.81)

PP

DSST

DWR

WF

MMSE

CDR

FAQ

MRI WMH

MCI: 19.8%W, 19.5%B

Dementia: 2.8%W, 4.3%B

Black and White adults with cerebrovascular disease have elevated cfPWV, central SBP, cPP. White individuals had higher central stiffness and pulsatility.

After adjustment to MAP the association of cfPWV with MCI or dementia is not significant

20

Waldstein S.R. et al., 2008

Baltimore longitudinal study of aging, US

Prospective study of community-dwelling volunteers

1958-start

11y and 14y – follow up

Gerontology research center

1749

Subset of 582 had PWV

53.3%M79.4W

57.1

128.8/80.1mmHg

22.1% HTNM

cfPWV (7.1±2.7)

PP

MAP

MMSE

WAIS

CVLT

BVRT

TMT-A, B

BNT

I-M-C

1. PP, cfPWV longitudinally predicted cognitive decline before dementia.

2. AS was higher in patients with cardiovascular and metabolic risk factors (MAP), and lower cognitive function.

3. Increased PP was associated with prospective decline of cognitive tests

21

Tsao C.W. et al., 2013

FHS

 (Framingham Heart Study), US

Population-based observational cohort, cross-sectional analysis

Since 1948

FHS G3 and offspring cohort, Examination 7

1587

45%M

61±9

126/74mmHg

30% HTNM

cfPWV (9.0)

MAP

cPP

LMDR

Trials B-A

MRI

(TCBV=79±3, WMHV=0.05, Silent cerebral infarct= 10%)

1.Higher cfPWV was associated with lower TCBV, larger WMHV, prevalent silent cerebral infarct

2. MAP, cPP were associated with greater WMHV, lower TCBV, worse verbal memory

3. Increased stiffness and pressure pulsatility were associated with brain aging, AD

22

Tsao C.W. et al., 2016

FHS

 (Framingham Heart Study), US

Population-based observational cohort

Since 1948

FHS G3 and offspring cohort,

Examination7 and 8

1223

56%F

61±9

SBP 125±18

28% HTNM

cfPWV (9.0) AP

cPP

Trials B-A

MRI

1. Higher cfPWV, cPP were associated with greater progression of neurocognitive decline

2. Higher MAP, not cfPWV and cPP was associated with increased WMH

3. Increased cfPWV and PP were associated with longitudinal progression of subclinical brain injury and greater cognitive decline4. Treatment of arterial stiffness reduced cognitive decline

23

Poels M.M.F. et al., 2007

Rotterdam Study, Netherlands

Population-based prospective cohort

1990-start

1997-1999

2002-2004

Population of Rotterdam

2767

42.3%M

72.0

MAP 106.7mmHg

cfPWV (13.2±2.9)

Carotid distensibility

PP

MAP

MMSE – dementia

NINCDS-ADRDA

NINCDS-AIREN – VD

LDST

Stroop test

WF

1. No association between AS and cognitive decline or risk of dementia after adjustment for cardiovascular risk factors

2. Higher AS was associated with higher SBP, PP, atherosclerosis

24

Poels M.M.F. et al., 2012

Rotterdam Study, Netherlands

Population-based prospective cohort,

cross-sectional analysis

1990-2004

Population of Rotterdam

1460

55.4%F

58.2

130/79.8mmHg

MAP 96.5mmHg

cfPWV (9.0±1.6)

MRI

WM lesion=2.2ml

Lacunar infarct=4.3%

Cerebral microbleeds 10.1%

1.Increased cfPWV was associated with larger WMH volume2. Uncontrolled HTN, high aoPWV was associated with larger WMH and cerebral microbleeds

25

Zhong W.J. et al., 2014

EHLS-BDES

(Epidemiology of Hearing Loss Study – Beaver Dam Eye Study), US

Longitudinal cohort,

cross-sectional analysis

1989-start

1. 5y

2. 15y

Beaver Dam residents

1433

43%M

75

61.4-75.8%

65-71% HTNM

cfPWV (11.0±3.6)

crPWV (10.0±2.3)

MMSE

TMT-A, B

DSST

AVLT

VFT

1. cfPWV was associated with lower MMSE score, AVLT, TMT-B.2. crPWV was not associated with cognitive tests3. Large arteries stiffness was associated with worse cognitive function

4. Increased AS operates through HTN to decrease cognitive function

26

Lin CH, et al., 2022

LAST

(Longitudinal Aging Study of Taipei), Taiwan

Community-based prospective ongoing, cross-sectional analysis

6y

Community in Taiwan

992

69.5%F

67.3

30.4%

25.7%HTNM

cfPWV (11.0±2.8)

Zc

carotid AI

carotid AP

Pf

Pb

XSPI, %XSPI

MoCA

MMSE

AS markers (XSPI/%XSPI), but not cfPWV were significantly higher in participants with low MoCA score due to vascular aging

27

Rensma S.R. et al., 2020

Maastrich Study, Netherlands

Population-based observational cohort, cross-sectional analysis

3y

S. Netherlands

2544

51%M

59.7

MAP 96.6mmHg

37.7% HTNM

cfPWV

carotid distensibility coefficient

MRI

VLT

SCWT part I-II-III

CST part A-B-C

LDST

Microbleeds=12.0

Lacunar infarct=5.3

1. Aortic stiffness, but not carotid stiffness was independently associated with worse cognition2. Increased aoPWV may lead to microvascular dysfunction via increased pulsatility load

28

Heffernan K.S. et al., 2022

NHANES

(National Health and Nutrition Examination Survey), US

Examination survey with serial cross-sectional design

1999-2002 enrollment.

3y

Noninstitutionalized population of all 50 states and Washington DC

3616

54.9%F

26.5%B

69.71

54%

ePWV (11.02)

DSST

1. PWV in older Black and White was inversely associated with DSST score (cognitive measure)2. BP has a mediating effect on AS and cognitive aging