Association Between Ambulatory 24-Hour Blood Pressure Levels and Cognitive Performance: A Cross-Sectional Elderly Population-Based Study

Abstract

Objective:

The aim of this study was to examine the cross-sectional association between ambulatory 24-h blood pressure levels and cognitive performance while considering the effects of potential confounders among community-dwelling adults aged 65 years and older.

Methods:

Based on a cross-sectional design, 1011 subjects (mean age 66.2 ± 0.8 years; 60.2% women) were recruited prospectively. Average levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were computed for a 24-h period. Cognitive performance was assessed by Folstein's Mini-Mental State Examination, immediate and delay recall subtests of the French version of the Free and Cued Selective Reminding Test, and Trail Making Test A and B. Age at baseline evaluation, gender, education level, anxiety, depression, cardiovascular risk factors, antihypertensive drugs use, and body mass index were used as confounders in data analysis.

Results:

Multivariate logistic regression showed that, compared with low DBP level (i.e., <80 mmHg) used as reference value, only a high DBP level (i.e., ≥90 mmHg) was significantly associated with lower performance in immediate recall (adjusted odds ratio [OR] = 2.7 [1.3;5.9] for full model, and adjusted OR = 2.6 [1.2;5.4] for the stepwise backward model). Furthermore, the stepwise backward selection showed that male gender (adjusted OR = 2.2 [1.4;3.3]) and depression (adjusted OR = 2.4 [1.3;4.6]) were also significantly associated with low performance in immediate recall, whereas a high education level was associated with high performance (adjusted OR = 0.9 [0.8;0.9]).

Conclusions:

The findings show that only high DBP was associated with lower episodic memory performance compared with low DBP level in the studied sample. Further research is needed to corroborate and explain this finding.

Introduction

T he association between abnormal blood pressure levels and cognitive dysfunction is now well established.^1,2 Changes in cerebral blood flow or in brain structure induced by atherosclerotic changes in cerebral arteries might account for the blood pressure–related cognitive changes.^2

–5 Results of previous epidemiologic studies have varied greatly. Some studies failed to find any association, whereas others reported a linear or a nonlinear relationship.^{1

–25} Furthermore, both high and low blood pressure have been associated with low cognitive performance among older adults.¹ These mixed results raise a number of issues that mainly concern the technique of blood pressure assessment, the suitable neuropsychological assessment used to detect cognitive dysfunction, and the control for confounders such as age and cardiovascular risk factors.

The technique of blood pressure assessment may be a source of mixed results. Occasional clinical blood pressure measurements poorly reflect blood pressure levels compared with ambulatory 24-h blood pressure monitoring.¹⁶ This last technique has been seldom used in comparison to clinical blood pressure measurement.^{2,16

–25} Since the development of the ambulatory 24-h blood pressure monitoring device, much information that had not previously been obtainable from clinical blood pressure measurement became available.^16

–20 For instance, ambulatory 24-h blood pressure monitoring provided information on the diurnal rhythm of blood pressure, the blood pressure variability, and the duration of drug effect. Furthermore, accumulated findings indicate that ambulatory 24-h blood pressure monitoring better predicts cardiovascular events than clinical blood pressure measurements.^16

–19 Therefore, ambulatory 24-h blood pressure monitoring could be a good way to examine the association between abnormal blood pressure levels and cognitive dysfunction. Few studies used ambulatory 24-h blood pressure monitoring with the aim to explore this association.^{17

–25}

Mixed results about the association between abnormal blood pressure levels and cognitive dysfunction may also be related to the assessed cognitive function. Various cognitive functions have been constantly reported as modified by blood pressure levels.^2,6,9 Memory is likely to be one of the most sensitive domains in which a high blood pressure–related reduced performance can be identified.^2,20 Furthermore, differences in findings of prior studies may be due to the poor availability of neuropsychological tests that show slight changes in specific cognitive function.²⁰

Many other confounders make difficult the construction of a clear and consistent picture across different studies on blood pressure–related cognitive function changes. Advance in age, gender, cardiovascular risk factors, the use of antihypertensive drugs, and anxio-depressive symptoms are the most recurrent confounders that should be considered relevant to the entanglement between blood pressure levels and cognitive performance.^1,2 However, they were not systematically taken into account.¹ Thus, a lack of control of these confounders could also explain discordant previous results.

The objective of the study was to examine the cross-sectional association between ambulatory 24-h blood pressure average values and cognitive performance while considering the effects of confounders in a population-based sample of adults aged 65 years and older.

Methods

Participants

The PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events) study is a community-dwelling observational prospective cohort study designed to evaluate the prognostic value of autonomic nervous system activity levels on fatal and nonfatal cardiovascular and cerebrovascular events. The sampling and data collection procedures have been described in detail elsewhere.²⁶ In summary, from 2001 to 2002, among the 3983 eligible subjects born between January 1, 1934, and September 30, 1936, and registered on the electoral list of Saint-Etienne (a midsized town in Eastern France), 1011 subjects (25.4%) were included after having given their written informed consent. The 3983 eligible subjects were contacted by mail. The volunteers returned a phone call to manifest their intention to participate in the study and to evaluate exclusion criteria. Exclusion criteria were previous myocardial infarction, previous stroke, heart failure, atrial fibrillation, insulin-dependant diabetes mellitus, cardiac pacemaker, disease limiting life expectancy below 5 years, contraindication to brain magnetic resonance imaging (MRI), living in an institution, and intention to move within the next 2 years. The cardiovascular exclusion criteria used in this study allowed in part controlling a potential interaction in the association between blood pressure levels and cognitive performance. Among the 3983 eligible subjects, 2660 (66.8%) subjects gave no answer, 443 (11.1%) refused to participate, and 49 (0.01%) were considered as ineligible. The sample was completed by the participation of some couple members (n = 48; 0.01%) and a few voluntary subjects (n = 132; 3.3%). All included subjects underwent a complete clinical examination by physicians at Saint-Etienne University Hospital. Information was gathered about cardiovascular risks, the use of antihypertensive drugs and anthropometry measurements.

Blood pressure measurement

Noninvasive arterial blood pressure measurement was assessed by ambulatory 24-h blood pressure monitoring using the auscultatory method (Diasys Integra, Novacor®, Rueil-Malmaison, France) on a weekday, starting early in the morning. Measurements were taken at the nondominant arm, every 15 min during the day and every 30 min at night. Patients were instructed to adhere to their normal daily activities and regular sleeping hours. Average levels of SBP and DBP were computed for a 24-h period and were used for data analysis.

Neuropsychological tests

Neuropsychological evaluation was performed during a face-to-face examination carried out by a neuropsychologist. Different tests were used to probe several aspects of cognitive function. First, global cognitive efficiency was evaluated with Folstein's Mini-Mental State Examination (MMSE).²⁷ This 30-point test assesses orientation in time and space, instantaneous recall and short-term memory, attention and calculation ability, and language and visual-constructive ability. A score of 25 or less indicates cognitive impairment. Second, verbal episodic memory was evaluated using immediate and delayed recall, which are two subtests of the French version of the Free and Cued Selective Reminding Test (FCSRT).^28,29 Immediate recall is a free immediate recall of a 16-word list previously showed, whereas delayed recall is a free recall of the list 20 min later. High scores on this standardized test denote a high memory performance. Third, executive functions were assessed by means of the Trail Making Test (TMT), a neuropsychological test evaluating two specific aspects of executive functions, which are the visual attention and the task switching.³⁰ This test requires a subject to “connect-the-dots” of 25 consecutive targets on a sheet of paper or computer screen. Two versions are available: Part A in which the targets are all numbers (1, 2, 3, etc.), and part B in which the subject alternates between numbers and letters (1, A, 2, B, etc.). The goal is to finish the test as quickly as possible, and the time taken to complete the test is used as the primary performance metric. Depressive symptoms were measured using the QD2A questionnaire including 13 questions.³¹ QD2A scores are ranged from 0 to 13 points. Anxiety was assessed using the French version of the Goldberg scale, a 9-item scale with scores ranging from 0 to 9.³²

Covariates

Age at baseline evaluation, gender, education level, anxiety, depression, cardiovascular risk factors, the use of antihypertensive drugs, and body mass index (BMI) were used as confounders in data analysis. Education level was evaluated with the number of years at school. The highest level of education corresponded to the highest number of years at school. Subjects with a score >4 at the French version of the Goldberg scale were considered as anxious and those who had a score >6 at QD2A questionnaire were considered as having depression symptoms.^31,32 Cardiovascular risk factors (i.e., type 2 diabetes, the use of antihypertensive drugs, smoking, alcohol use, and hypercholesterolemia) were recorded during medical interview. Type 2 diabetes was considered to be present in case of the use of oral antidiabetic drugs. Antihypertensive drugs use is defined by the use of at least one of the following drug therapies: renin–angiotensin inhibitor agents, beta-blocking agents, diuretics, calcium channel blockers, and central antihypertensive agents. The use of antihypertensive drugs was collapsed into a single “Yes” versus “No” category. The smoking status was defined as current or former smoker versus nonsmoker. Alcohol consumption was collapsed into the two following categories: Regular versus nonregular consumer of beer, wine, or spirits. Hypercholesterolemia was defined as a total cholesterol level exceeding 6.5 mmol/L and/or use of lipid-lowering drugs.

Data analyses

The subjects' baseline characteristics (i.e., systolic blood pressure [SBP], diastolic blood pressure [DBP], age, cardiovascular risk factors, antihypertensive drugs, BMI, anxio-depressive symptoms, and education level) and scores of the neuropsychological tests (i.e., MMSE, FCSRT, and TMTA and B) were summarized using means and standard deviations or frequencies and percentages, as appropriate. First, comparisons between groups were performed using the independent samples t-test for continuous variables, and chi-squared test for categorical variables. Second, the association between blood pressure and memory decline was investigated with univariate and multivariate logistic regression analyses, using low blood pressure as the reference category. A stepwise backward variables selection method was then applied to identify the most relevant predictors. Based on blood pressure thresholds chosen from the risk categories defined by the American Heart Association,^33,34 blood pressure levels were classified into three categories, on the basis of SBP (low <120 mmHg; moderate 120–139 mmHg; high ≥140 mmHg), and DBP (low <80 mmHg; moderate 80–89 mmHg; high ≥90 mmHg), respectively. All models were adjusted for the following covariates: Age, gender, education level, anxiety, depression, cardiovascular risk factors, use of antihypertensive drugs, and body mass index. A score of 25 or less at MMSE was considered to indicate cognitive impairment. Memory and executive low performance were defined as being in the worst quintile of performance in FCSRT and TMT. p values less than 0.05 were considered as statistically significant. All statistics were performed using the Stata Statistical Software, release 10.1.³⁵

Results

The baseline characteristics of all participants are summarized in Table 1. 60.2% were women. There was no gender difference for age and the use of antihypertensive drugs (p = 0.692 and p = 0.794, respectively). The diagnosis of diabetes was less frequent in women than men (p < 0.001). Alcohol and cigarette consumption were lower in women than men (p < 0.001), whereas women presented more anxio-depressive symptoms and were more anxious (p < 0.001). BMI was lower in women than men (p < 0.001). The mean values of SBP and DBP were normal (119.0 ± 14.0 mmHg and 76.0 ± 7.9 mmHg, respectively). Women had lower mean value of blood pressure and education level compared with men (p < 0.001 and p = 0.013, respectively). The mean value of MMSE score was normal without significant differences between women and men (p = 0.819). Only 38 subjects (3.8%) had an abnormal score. Women had better scores in episodic memory tests than men (p < 0.001). There was no significant difference between women and men in both TMT performance (p = 0.225 for test A and p = 0.223 for test B). There were significantly more men then women in the worst quintile for the TMT B (22.7% versus 17.0%, p = 0.032). Compared with low DBP level (i.e., <80 mmHg) used as reference value, only high DBP level was significantly associated with a lower score at the immediate recall test (adjusted odds ratio [OR] = 2.7 [1.3;5.9]) for the full model (Table 2). As shown in Table 3, a low performance in immediate recall was significantly associated with male gender (crude OR = 2.2 and adjusted OR = 2.2 with p < 0.001), depression (crude OR = 2.1 with p = 0.006 and adjusted OR = 2.4 with p = 0.008), and a DBP ≥90 mmHg (crude OR = 3.2 with p < 0.001 and adjusted OR = 2.6 with p = 0.013), whereas a high education level was associated with a high performance (crude OR = 0.9 with p = 0.007 and adjusted OR = 0.9 with p = 0.004).

Table 1.

Subjects' Baseline Characteristics (n = 1011)

	Women	Men	Missing values ^a	Total	p Value ^b
n (%)	609 (60.2)	402 (39.8)	—	1011 (100.0)	<0.001
Age, mean ± SD (years)	66.2 ± 0.8	66.2 ± 0.7	0	66.2 ± 0.8	0.692
Cardiovascular risk factors
Diabetes, n (%)	18 (3.0)	39.8 (9.7)	0	57 (5.6)	<0.001
High total cholesterol, n (%)	246 (40.5)	135 (33.6)	1	381 (37.7)	0.027
Alcohol, n (%)	183 (30.2)	269 (67.6)	7	452 (45.0)	<0.001
Smoking, n (%)	111 (18.3)	253 (63.1)	2	364 (36.1)	<0.001
Antihypertensive drugs, n (%)	140 (24.5)	94 (25.3)		234 (24.8)	0.794
Body Mass Index, mean ± SD	24.9 ± 4.2	25.9 ± 3.1	152	25.3 ± 3.9	0.001
ASBP: Mean/24 h (mmHg)
Mean ± SD	116.9 ± 13.7	122.1 ± 13.7	114	119.0 ± 14.0	<0.001
Low (<120 mmHg), n (%)	357 (60.6)	186 (46.7)		543 (55.0)	<0.001
Medium (120–139 mmHg), n (%)	199 (33.8)	168 (42.2)		367 (37.2)
High ( ≥ 140 mmHg), n (%)	33 (5.6)	44 (11.1)		77 (7.8)
ADBP: Mean/24 hours (mmHg)
Mean ± SD	74.3 ± 7.6	78.5 ± 7.7	114	76.0 ± 7.9	<0.001
Low (<120 mmHg), n (%)	462 (78.4)	238 (59.8)		700 (70.9)	<0.001
Medium (120–139 mmHg), n (%)	107 (18.2)	128 (32.2)		235 (23.8)
High ( ≥ 140 mmHg), n (%)	20 (3.4)	32 (8.0)		52 (5.3)
Depression^c (/13)
Mean ± SD	3.1 ± 3.0	1.9 ± 2.1	83	2.7 ± 2.8	<0.001
>6, n (%)	69 (12.3)	13 (3.5)		82 (8.8)	<0.001
Anxiety^d (/9)
Mean ± SD	4.0 ± 3.0	2.6 ± 2.5	79	3.4 ± 2.9	<0.001
>4, n (%)	278 (49.5)	93 (25.1)		371 (39.8)	<0.001
Education level,^e mean ± SD	10.8 ± 2.6	11.3 ± 3.3	89	11.0 ± 2.9	0.013
Global cognition
MMSE score (/30), mean ± SD	28.4 ± 1.8	28.5 ± 1.5	11	28.4 ± 4.7	0.819
MMSE score < 25, n (%)	28 (4.6)	10 (2.5)		38 (3.8)	0.093
Episodic memory^f
Immediate recall (/16)
Mean ± SD	15.5 ± 0.8	15.1 ± 1.2	78	15.3 ± 1.0	<0.001
Worst quintile
Mean ± SD	13.7 ± 0.6	13.2 ± 1.0		13.4 ± 0.9
n (%)	63 (11.2)	80 (21.6)		143 (15.3)	<0.001
Delayed recall (/16)
Mean ± SD	15.8 ± 0.6	15.3 ± 1.3	78	15.6 ± 1.0	<0.001
Worst quintile
Mean ± SD	13.4 ± 1.5	13.0 ± 1.4		13.1 ± 1.4
n (%)	20 (3.6)	69 (18.7)		89 (9.5)	<0.001
Executive function
Trail Making Test A
Mean ± SD	48.1 ± 15.8	47.3 ± 16.0	79	47.8 ± 15.9	0.225
Worst quintile
Mean ± SD	29.6 ± 3.3	29.6 ± 3.8		29.6 ± 3.5	0.936
n (%)	106 (18.9)	78 (21.0)		184 (19.7)	0.424
Trail Making Test B
Mean ± SD	106.3 ± 49.7	103.6 ± 51.2	91	105.2 ± 50.3	0.223
Worst quintile
Mean ± SD	56.8 ± 7.0	56.3 ± 7.6		56.6 ± 7.3	0.646
n(%)	94 (17.0)	83 (22.7)		177 (19.2)	0.032

Expressed in number of missing observation.

Comparison between women and men based on independent samples t-test or chi-squared test, as appropriate.

Depressive symptoms measured using the QD2A questionnaire including 13 questions with scores ranging from 0 to 13 points.

Assessed with the French version of the Goldberg scale including 9 questions with scores ranging from 0 to 9.

Assessed with the number of years at school.

Assessed with the French version of the Free and Cued Selective Reminding test.

SD, Standard deviation; ASBP, ambulatory systolic blood pressure; ADBP, ambulatory diastolic blood pressure; MMSE, Folstein's Mini Mental State Examination.

Table 2.

Multivariate Logistic Regression Showing the Cross-Sectional Association Between Blood Pressure and Cognitive Performance Adjusted for Potential Confounders ^a

	Global cognition	Episodic memory		Executive functions
	MMSE ^b OR [95% CI]	Immediate recall ^c OR [95% CI]	Delayed recall ^c OR [95% CI]	Trail making test A ^c OR [95% CI]	Trail making test B ^c OR [95% CI]
Systolic blood pressure^d
Low (<120 mmHg)	1	1	1	1	1
Medium (120–139 mmHg)	1.6 [06;4.1]	0.9 [0.6;1.4]	1.1 [0.6;2.0]	1.1 [0.8;1.7]	0.8 [0.5;1.2]
High ( ≥ 140 mmHg)	0.8 [0.1;8.5]	1.9 [0.9;3.8]	1.2 [0.5;3.1]	0.8 [0.3;1.7]	1.4 [0.7;2.9]
Diastolic blood pressure^d
Low (<80 mmHg)	1	1	1	1	1
Medium (80–89 mmHg)	2.1 [0.7;6.6]	1.1 [0.7;1.8]	1.1 [0.6;2.1]	1.0 [0.6;1.6]	0.9 [0.6;1.5]
High ( ≥ 90 mmHg)	2.8 [0.3;28.0]	2.7 [1.3;5.9]	1.7 [0.6;4.6]	0.4 [0.1;1.3]	1.1 [0.4;2.6]

Significant odds ratios (i.e., P < 0.05) indicated in boldface.

Adjusted for age, gender, education, anxiety, depression, cardiovascular risk factors, use of antihypertensive drugs, and body mass index.

Impaired performance defined as MMSE score <26/30.

For each test, poor cognitive function indicated by being in the worst quintile.

Separated model for systolic and diastolic blood pressure.

OR, Odds ratio; CI, confidence interval; MMSE, Folstein's Mini-Mental State Examination (max 30).

Table 3.

Uni- and Multivariate Logistic Regression Showing the Cross-Sectional Association Between Being in the Worst Quintile on Immediate Recall and Explicative Baseline Characteristics ^a

Variables	OR unadjusted	[95% CI]	p Value	OR adjusted	[95% CI]	p value
Male gender	2.2	[1.5; 3.1]	<0.001	2.2	[1.4; 3.3]	<0.001
Depression^b	2.1	[1.2; 3.6]	0.006	2.4	[1.3; 4.6]	0.008
Education level^c	0.9	[0.8; 0.9]	0.007	0.9	[0.8; 0.9]	0.004
High diastolic blood pressure^d	3.2	[1.7; 6.0]	<0.001	2.6	[1.2; 5.4]	0.013

Significant odds ratios (i.e., p < 0.05) indicated in boldface.

Baseline characteristics selected from backward stepwise model.

Based on the QD2A questionnaire with a score above 6 points (/13).

Expressed in number of years at school and centered on the mean value.

Diastolic blood pressure ≥90 mmHg.

OR, Odds ratio; CI, confidence interval.

Discussion

Our results show that there was an association between blood pressure levels and verbal episodic memory performance in the studied sample of elderly subjects. The association differed according to the type of blood pressure (DBP versus SBP) and the verbal episodic memory performance (immediate versus delay recall). Compared with low DBP level (i.e., <80 mmHg) used as reference value, only high DBP level (i.e., ≥90 mmHg) was associated with lower performance in immediate recall. Furthermore, logistic regression analysis showed that male gender and depression were also associated with low performance in immediate recall, whereas a high education was associated with high performance.

Numerous studies have attempted to describe the relationship between blood pressure levels and cognitive performance in older adults.^{1

–25} Most of them have shown that high blood pressure levels were associated with a decline in cognitive performance, but few of them used ambulatory 24-h blood pressure monitoring in comparison to clinical blood pressure measurement.^{18

–25} Ambulatory 24-h blood pressure monitoring has several advantages while considering blood pressure measurement compared with clinical blood pressure measurements.¹⁶ Prolonged monitoring permits a direct blood pressure evaluation by measuring it as a temporal sequence of numerical values. This approach can also be used to investigate the circadian blood pressure profile.²¹ Furthermore, it is a way to avoid the influence of the “white-coat effect” (WCE), which may lead to overestimated blood pressure levels.³⁶ It is well-known that blood pressure measurements taken by a physician tend to be higher than those obtained by a nurse,³⁷ and blood pressure measured in a clinic setting is usually higher than out-of-office readings.³⁸

Ambulatory 24-h blood pressure monitoring and clinical blood pressure measurements provided mixed results while exploring the association between blood pressure levels and cognitive dysfunction.^{17

–25} While some studies failed to find any association,^17

–20 others showed that abnormal blood pressure levels were associated with lower cognitive performance compared with normal values.^21

–25 Apparent discordant findings may be related to the method used to measure blood pressure. Abnormal SBP levels have been more frequently related to lower cognitive performance compared with DBP levels.^21

–25 Two studies showed a significant association between low night-time DBP and low cognitive performance,^23,24 whereas one study, similar to our results, found that high 24-h DBP was associated with low cognitive performance.²⁵

Mixed results may be also related to the type of neuropsychological test used in different studies. It has been shown that the association between blood pressure levels and cognitive performance is often limited to specific cognitive functions.^1,15 Memory and attention appear particularly vulnerable to elevated blood pressure levels.^2,20,39,40 In contrast to most previous cross-sectional studies, which limited the cognitive assessment to unspecific tests such as the MMSE,^1,27 we chose to examine also a more vulnerable cognitive function such as memory by means of two specific memory tests—the immediate and delay recall subtests. The main difference between these two verbal episodic memory subtests is a high involvement of attention in immediate recall compared with delay recall.^28,29 Thus, immediate recall is a test combining an expertise of the more vulnerable cognitive function regarding high blood pressure^20,39,40 and, therefore, appears to be a more sensitive test than delay recall test for the detection of hypertension-related memory changes. This point could be related to prior result on healthy subjects that showed a decline in immediate recall due to altitude-related oxygenation reduction.⁴¹ Whereas severe hypoxemia leads to irreversible brain damage, mild to moderate hypoxemia may affect more specific cognitive functions such as immediate recall.^2,3 In addition, the low memory performance shown in our study is in concordance with results reported among early demented subjects with a low performance in tests involving both attention and episodic memory.^1
–3

The specificity of the association between high DBP and cognitive decline in verbal episodic memory performance remains unclear. The mechanisms linking elevated blood pressure and poor cognition are thought to involve subtle disturbance in cerebral perfusion,² which are then thought to have an adverse effect on the brain cell metabolism.^1,3 Hypertension accelerates atherosclerotic changes in the brain, predisposing to atheroma formation in both large- and small-diameter blood vessels; this leads to a reduction in the perfusion of capillary bed and thus results in discrete lacunar infarctions and/or more diffuse ischemic changes in white matter, known as leukoaraiosis.^1

–4 Cerebral imaging studies have also shown that a high blood pressure is related to the presence and severity of white matter lesion load.^1,2,17,42 Furthermore, cognitive decline is correlated with cerebral hypoperfusion in subjects with established ischemic small vessels diseases.^17,42 These consequences of high blood pressure–related modifications could explain the low memory performance in our sample of subjects. Hypertension is related to a spectrum of brain ischemic-related changes that might be clinically asymptomatic but have an impact on cognitive ability. Our cohort was examined at an early stage of the hypertension disease, which may explain why high and not low blood pressure level was related to memory performance.

Education and depression symptoms accounted for a considerable degree of the variance of the cognitive function tests scores,^1,14,43 and, therefore, they should be considered while assessing the relationship between blood pressure and memory performance. Our findings are consistent with prior results and corroborate that the highest memory performance were reported among subjects with a high education level.^2,20,39,40 Additionally, depression symptoms, according to the QD2A questionnaire in our study, were related to a low memory performance. This is consistent with a prior study which established the cross-sectional association between depression symptoms and scores of memory tests in older adults.^1,43

Some limitations of this study need to be considered. First, our subjects were relatively highly motivated and had probably a great interest in health issues; therefore, they might not be representative of the general population of community-dwelling older adults. Second, only 25.4% of subjects of the targeted population were included in our study. However, this problem of exclusion is a general problem of epidemiologic studies. Most of them included in the final less than 30% of the population targeted. Third, compared with the prospective follow-up design, the examination of the correlation between blood pressure and memory performance might be limited by the cross-sectional design of our study. Similarly, this design restrained the determination of the direction of the association between blood pressure levels and cognitive dysfunction because both parameters were assessed simultaneously. Fourth, although we were able to control for many confounders that are likely to modify this relationship, residual potential confounders might persist.

The present cross-sectional study showed that high DBP (i.e., ≥90 mmHg), and not SBP, was associated with low episodic memory performance. This association suggests that low memory performance could be an early adverse consequence of high blood pressure levels on the brain. Further research is needed to corroborate and explain this finding.

Footnotes

Acknowledgments

The PROOF study group would like to thank all persons who took part in this study—Dr. Catherine Thomas-Anterion, Mrs. Delphine Maudoux, Dr. Stéphane Chomienne, and Mr. Arnault Garcin (Saint–Etienne University Hospital, France)—for their expert help in data acquisition and interpretation.

Author Disclosure Statements

The authors have no relevant financial interest in this manuscript. Author contributions were as follows: Beauchet had full access to all study data and takes responsibility for the integrity of the data and the accuracy of the data analyses; Roche and Barthelemy, study concept and design; Kerleroux, Pichot, Celle, acquisition of data; Beauchet, Herrmann, Roche, analysis and interpretation of data; Beauchet, Roche, Barthelemy, drafting of the manuscript; Gosse, Pichot, Celle, Annweiler, Barthelemy, critical revision of the manuscript for important intellectual content; Barthelemy, obtained funding; Herrmann, statistical expertise; Roche, Barthelemy, administrative, technical, or material support; Roche, Barthelemy, study supervision.

This study was supported by a grant from the French Minister of Health (Cellule Projet Hospitalier de Recherche Clinique National, Direction de la Recherche Clinique, CHU Saint-Etienne; Appel d'Offre 1998 and Appel d'Offre 2002) and by Association de Recherche SYNAPSE (Michel Ségura: President).

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