RELATIONSHIP BETWEEN BLOOD PRESSURE COGNITION AND EDUCATION LEVEL IN

relationship between blood pressure, cognition, and education level in elderly patients with diabetes mellitus: preliminary study j. talfou

RELATIONSHIP BETWEEN BLOOD PRESSURE, COGNITION, AND EDUCATION LEVEL IN
ELDERLY PATIENTS WITH DIABETES MELLITUS: PRELIMINARY STUDY
J. Talfourniera, J. Bitua, C. Paquetc,d, C. Gobrone, PJ. Guillausseaua,b,
J. Hugonc,d, J. Dumurgierc,f,*
a Service of Internal Medicine B, AP-HP, Hopital Lariboisière,
University Paris 7 Denis-Diderot, Paris, France
b INSERM UMR-S 958, University Paris 7 Denis-Diderot, Paris, France
c Centre Memoire Ressources Recherche Paris Nord Ile-de-France, AP-HP,
Saint Louis - Lariboisiere - Fernand Widal Hospital, Univ Paris
Diderot, Sorbonne Paris Cité, Paris, France
d INSERM U839, Institut du Fer à Moulin, Paris, France
e Physiologie Clinique-Explorations Fonctionnelles, AP-HP, Hôpital
Lariboisière, Paris, France
f INSERM U1018, Centre for research in Epidemiology and Population
Health, Villejuif, France
J. Talfournier and J. Bitu contributed equally to this work.
Running title: Blood pressure and cognition
* Corresponding author. Tel.: +33 140 054 313; fax: +33 140 054 339.
E-mail address: [email protected] (J. Dumurgier).
Word count: Text 2 431 words + 4 tables and 1 figure (500 x 5=2 500)
total 4 931 words
40 references
Abstract
Aims. To study the relationship between blood pressure and cognitive
functions in elderly patients with diabetes mellitus (DM).
Methods. 32 patients with DM aged 65 years and over were included in a
cross-sectional study (7 women/25 men, mean (SD) age 74.36.4 years).
Relationships between blood pressure and neuropsychological tests were
studied using Spearman’s rank correlations (ρ) and multivariable
linear regression models.
Results. A lower diastolic blood pressure was associated with a lower
score at the Frontal Assessment Battery (ρ=0.32, P=0.02), a longer
time at Trail Making Test B assessment (ρ=0.51, P=0.003), a lower
score at the Finger Tapping Test (ρ=0.36, P=0.046), and a reduced
verbal fluency (ρ=0.36, P=0.047). In multivariable models, these
relationships were attenuated after adjustment for levels of
education.
Conclusion. We report an association between lower diastolic blood
pressure and poorer executive function in a cohort of elderly patients
with DM. These results underline the interest of a systematic
evaluation of cognition in elderly patients with diabetes, and suggest
that a too low diastolic blood pressure may have deleterious effects
on cognition. Future larger studies are required to confirm these
preliminary results.
Keywords: Diabetes mellitus; Elderly, Blood pressure; Cognition;
Executive functions; Education level
French title. Relation entre pression artérielle, cognition et niveau
d’éducation chez le sujet âgé diabétique : étude préliminaire.
Résumé
Objectif. Etudier la relation entre le niveau de pression artérielle
et les fonctions cognitives parmi une population de sujets diabétiques
âgés.
Méthodes. 32 patients diabétiques âgés de 65 ans et plus ont été
inclus dans une étude transversale (7 femmes/25 hommes, âge moyen DS
74,36,4 ans). Les relations entre la pression artérielle et les tests
neuropsychologiques ont été étudiées par des coefficients de
corrélation de Spearman (ρ) et par des modèles de régression linéaire
multivariés.
Résultats Une pression artérielle diastolique basse était associée à
un score plus faible à la Batterie Rapide d'Efficience Frontale
(p=0,32, P=0,02), un temps plus élevé au Trail Making Test B (p=0,51,
P=0,003), une moins bonne performance au Finger Tapping Test (p=0,36,
P=0,046), ainsi qu’à une diminution de la fluence verbale (p=0,36, P=0,047).
En analyse multivariée, ces relations étaient fortement atténuées
après ajustement sur le niveau d’éducation.
Conclusion. Nous rapportons une association entre une pression
artérielle diastolique basse et de moins bonnes fonctions exécutives
parmi une cohorte de sujets diabétiques âgés. Ces résultats soulignent
l’intérêt d’une évaluation systématique de la cognition chez les
patients diabétiques âgés, et suggèrent un potentiel effet délétère
d’une pression artérielle diastolique trop basse sur la cognition. Des
futures études plus larges seront nécessaires pour confirmer ces
résultats préliminaires.
Mots clés : Diabète ; sujet âgé, Pression artérielle ; Cognition ;
Fonctions exécutives ; Niveau d’éducation
1. Introduction
Diabetes mellitus (DM) is one of the most common diseases, affecting
over 170 million people worldwide. DM is associated with long-term
severe complications, secondary to macro and microvascular chronic
lesions . Several large observational studies have shown that subjects
with DM may have subtle changes in cognition compared to those without
DM , together with an increased risk of dementia . The pathological
neuropsychological pattern observed in patients with DM is usually
characterized by an impairment of executive functions , i.e. cognitive
processes involved in higher level organization and in execution of
complex thoughts and behaviour . The origin of these cognitive changes
remains poorly understood . The main hypotheses involve a direct
toxicity of hyperglycaemia , increase levels of oxidative stress , and
the chronic damage of small brain vessels observed in diabetes. Other
mechanisms may play a role in the pathogenesis of cognitive disorders
observed in patients with DM. Diabetes is indeed associated with an
increased risk of stroke in the elderly as well as vascular dementia .
Chronic or severe hypoglycaemia has also been shown to have
deleterious consequences on cognition . Some studies also suggest that
chronic insulin resistance observed in DM may play a role in the
pathogenesis of the lesions in Alzheimer’s disease . However, whether
DM represents an independent risk factor for Alzheimer’s disease
remains debated .
A better knowledge of the mechanisms involved in cognitive disorders
associated with DM is required, because of its consequences on
patients and their relatives. Furthermore, patients with impaired
cognition may have difficulties in managing and controlling their
treatment, leading to a worsening in diabetes control. Blood pressure
is known to play an important role in cognition in the elderly, due to
its consequences on brain perfusion and its role on cerebrovascular
disease pathogenesis . However, the relationship between blood
pressure and cognition appears to be complex, and if some studies
reported that midlife high blood pressure was associated with future
cognitive impairment , other studies have revealed that, in older
adults, a low blood pressure may also have a deleterious effect on
cognition . As hypertension represents a potential drug target, and is
a common feature in patients with DM , relationship between blood
pressure and cognition should be elucidated in these patients. Few
data are available concerning the relationship between cognition and
blood pressure levels in elderly patients with DM. Therefore, based on
an exploratory cohort of consecutive patients with DM explored in our
local diabetes center, we investigated the cross-sectional association
between neuropsychological evaluation and blood pressure level. We
hypothesized that a low diastolic blood pressure or a high systolic
blood pressure would be associated with poorer cognitive function in
elderly patients with DM.
2. Methods
2.1. Study population
The study population consisted of consecutive patients, explored in
our outpatient diabetes center between June 2011 and January 2012.
Inclusion criteria were diabetes mellitus, aged 65 years and older,
and to be French native speakers. Patients with history of disabling
stroke, prevalent known dementia, or impaired mobility were excluded.
The entire protocol was administered under routine care in the
diabetes department of the Lariboisière Hospital (Paris, France).The
physician in charge of the outpatient department (J.B.) screened and
included one patient per week, leading to a total of 32 patients at
the end of the study. As this work constitutes a preliminary study,
the objective was therefore limited to 30 patients for a discovery
cohort.
2.2. Blood pressure assessment
During the evaluation of patients, systolic blood pressure (SBP) and
diastolic blood pressure (DBP) were measured twice by a trained nurse,
at least after 5 min of rest in sitting position, with an
appropriately sized cuff placed on the right arm and using a single
validated digital electronic tensiometer. The mean of both measures
was used in the analyses. Blood pressure was determined before the
cognitive evaluation, and at distance of any blood sample procedure.
Pulse pressure was defined as the SBP minus the DBP.
2.3. Neuropsychological evaluation
All patients underwent a neuropsychological battery conducted by one
trained and experimented medical doctor (J.B.). The neuropsychological
battery included a global evaluation of cognitive efficiency with the
Mini Mental State Examination (MMSE), a questionnaire of cognitive
complaints (QPC), an evaluation of episodic memory using the Memory
Impairment Screen (MIS), and an evaluation of depressive symptoms with
the Center for Epidemiologic Studies Depression (CESD) scale.
Executive functions were tested using the Frontal Assessment battery
(FAB), the Trail Making Test (TMT) part A and B and verbal fluency (generating
words beginning with P in two minute). Psychomotor speed was also
evaluated using the Finger Tapping Test over 10 seconds. Normative
values of these tests and principals references are summarized in
supplementary table S1. All tests were proceed and reported according
to the standardized procedures. Among the 9 tests underwent by the
patients, 5 were centred on executive functions (FAB, TMT-A, TMT-B,
Finger Tapping Test, and verbal fluency). As a preliminary study
including a small sample, the idea was to evaluate the relevance and
the feasibility of those tests in patients with DM.
2.4. Other covariates
Baseline demographic and medical data were collected using
standardised questionnaires. Education was defined as a three level
variable (low: no school or primary level, medium: secondary level,
and high: baccalaureate or university degree). Characteristics of
diabetes were assessed using medical records and by interview of the
patient. Weight and height were measured and used to calculate body
mass index (BMI). The use of antidiabetic, antihypertensive, and
lipid-lowering drugs was also recorded. Fasting blood samples,
analyzed at a single local laboratory, were obtained to measure
fasting glycemia and glycated haemoglobin (HbA1c).
2.5. Statistical analyses
Correlations between blood pressure measurements and
neuropsychological tests were established using Spearman’s rank
correlations, 95% confidence intervals were computerized based on
Fisher's transformation. To test whether the association between blood
pressure and cognition was explained by potential confounders, we used
generalized linear regression models between blood pressure (as
dependant variable) and the various cognitive tests (as explicative
variable) adjusted successively for the following covariates : age and
sex ; hypertensive drugs ; BMI ; depressive symptoms ; diabetes
duration ; HbA1c ; and education level. The percentage reduction
(delta) of the association between blood pressure and cognitive test
attributed to covariates was calculated using the formula 100x(βunadjusted
- βcovariate) / βunadjusted, where β is the coefficient obtained from
generalized linear regression models.
P-values were two-tailed and values ≤0.05 considered as statistically
significant. Analyses were performed using SAS 9.2 (SAS Institute,
Cary, North Carolina, USA).
3. Results
32 patients with DM were included in the present study; their
characteristics (mean  SD) are presented in Table 1. Age of
participants was 74.36.4 years, 22% of them were women. Systolic
blood pressure was 133.518.2 mmHg (range: 100-168 mmHg), diastolic
blood pressure 68.19.9 mmHg (range 49-86 mmHg), and pulse pressure
was 65.316.3 mmHg (range 39-105 mmHg). Diabetes duration was 21.76.4
syears, 53% of the patients were treated with oral antidiabetic agents
only, 31% were treated with insulin only, and 16% were treated with a
combination of oral antidiabetic agents and insulin. Results of
cognitive evaluation are summarized in Table 1. MMSE scores ranged
between 20 and 30, FAB scores ranged between 9 and 18.
Table 2 shows Spearman’s rank correlation coefficients between blood
pressure and the various cognitive tests. A lower diastolic blood
pressure was associated with a lower score at FAB (ρ=0.32, Ρ =0.02), a
longer time at Trail Making Test B (ρ=-0.51, Ρ =0.003), a lower Finger
Tapping Test (ρ=0.36, Ρ=0.046), and a lower verbal fluency (ρ=0.36, Ρ=0.047).
Figure 1 illustrates the scatter plots of diastolic blood pressure
plotted with cognitive performances, with corresponding linear
regression lines. A higher pulse pressure was associated with a longer
time at Trail Making Test A (ρ=0.39, Ρ=0.03). There was no significant
relationship between systolic blood pressure and cognitive tests.
Relationship between diastolic blood pressure and cognitive function,
adjusted on potential confounders, are presented on Table 3.
Adjustment on age and sex, the use of antihypertensive drugs, BMI,
depressive symptoms, diabetes duration or HbA1c did not modify the
association between diastolic blood pressure and cognitive tests. By
contrast, adjusting for education level strongly attenuated the
relation between diastolic blood pressure and cognition, which was no
more significant: parameter of linear regression decreased by 42% for
FAB, and by 29% for TMT-B. In complementary analysis, a lower
education level was associated both with lower diastolic blood
pressure and lower cognitive performances (Table 4). Analysis based on
Finger Tapping Test and verbal fluency lead to similar findings (data
not shown).
4. Discussion
In this sample of elderly patients with DM, we observed that a lower
diastolic blood pressure was associated with poorer cognitive
functions. This relationship predominated on executive functions: a
lower diastolic blood pressure was associated with a lower score at
FAB, a lower Finger Tapping Test, a lower verbal fluency, and a higher
time at TMT-B. In multivariable analysis, we found that this
relationship was partly explained by the education level, which was
associated with both cognitive performances and diastolic blood
pressure, and also played the role of a confounding factor in the
observed relationship between diastolic blood pressure and cognition.
Several cross-sectional studies have shown that patients with type 2
diabetes have worse cognitive performances compared to subjects
without DM . However few data are available concerning the factors
that may influence the cognition among patients with DM . Chronic
hyperglycaemia, long diabetes duration, presence of a retinopathy or
microalbuminnuria have been reported to be associated with an
increased risk of cognitive impairment . Diabetes is also associated
with cerebrovascular disease , and poorer cognition has been
associated with the presence of lacunar infarcts , or white matter
abnormalities among patients with DM. Study of the relationship
between hypertension and cognition in diabetes has generated
conflicting results: some studies reported an association while others
did not . Relationships between blood pressure and cognition appear to
be complex , and results of epidemiological studies suggest that if
high blood pressure in midlife is linked to future cognitive decline,
low blood pressure may play a predominant role in later life . A lower
diastolic blood pressure was also recently associated with an
increased risk for poor outcomes in DM . Lower diastolic blood
pressure may therefore be considered as a marker of more severe course
in diabetes.
Several mechanisms may explain the deleterious effects of a low
diastolic blood pressure on cognition. A too low blood pressure may
induce a chronic cerebral hypoperfususion and a brain hypoxia leading
to subcortical lesions and cognitive dysfunction . Another mechanism
potentially involved is the association between a low diastolic blood
pressure and severe atherosclerosis . Atherosclerosis may leads to
cerebrovascular damage and cognitive dysfunction of vascular origin.
Chronic insulin resistance had also been shown to be associated with
Alzheimer type neuropathological brain lesions, especially in the
amyloid pathway . As a lower diastolic blood pressure is associated
with an increased risk of Alzheimer’s disease , we may hypothesize
that insulin resistance and low blood pressure may have synergic
deleterious effect on cognition.
We observed an association between low blood pressure and poorer
results at 4 tests assessing executive functions (FAB, Trail Making
Test B, Finger tapping test, Verbal fluency), but not with global
cognitive efficiency measured by the MMSE. This finding is consistent
with previous published literature which reports that
neuropsychological pattern observed in patients with DM is usually
characterized by an impairment of executive functions . The
dysfunction of executive tasks may not appear in the MMSE assessment.
In our study, the relationship we observed between diastolic blood
pressure and cognition was explained in part by the education level.
Indeed, a lower education level was associated with both lower
diastolic blood pressure and lower cognitive functions; and after
adjustment for education level, the relationship between diastolic
blood pressure and cognition was strongly attenuated. Previous studies
has shown that patients with DM with a lower level of education have
more long-term diabetes complications , more cardiovascular diseases ,
and an increased risk of total mortality compared to patients with DM
with higher levels of education. Education level is known to strongly
impact the neuropsychological assessment . The reason why we observed
an association between lower blood diastolic pressure and lower
education level remains unknown. We may hypothesize that lower
diastolic blood pressure may reflect a more severe disease in elderly
patients with DM .
Some limitations of our study must be considered. Because of the small
size of the study sample, correlation coefficients are more
susceptible to outliers. To decrease this risk, we used Spearman’s
rank correlations which consider correlations in rank. The small size
of our sample also did not allow incorporating a large number of
variables in multivariable models. The proportion of women in our
sample was low and therefore may be not representative of the general
population of patients with DM. Another limitation of this study is
its cross-sectional design. Future work with longitudinal repeated
assessment of cognitive function will be necessary to better
understand the complex relationship between blood pressure, education
level and cognition observed in diabetes mellitus.
In conclusion, we reported an association between lower diastolic
blood pressure and poorer executive functions in a population of
elderly patients with DM. In multivariable analysis, this association
was partly explained by level of education of the patients. Our
results underline two important points. First, the evaluation of
cognitive function in patients with diabetes is meaningful and should
be systematically integrated in the clinical setting. Current
recommendations for the management of glucose control in older people
with DM are based on a “patient-centered approach” , and cognition has
to be taken into account. Second, our results reinforce the growing
literature which reports that a too low diastolic blood pressure may
have deleterious effects, especially on the cognition of oldest
patients. As a preliminary study, we demonstrated in a small sample
that it was possible to integrate a neuropsychological battery to
evaluate patients who were assessed by a physician not specialized in
cognitive disorders. In a second phase, we aim to follow a large and
multicentric cohort of patients with DM, with repeated measurement of
cognitive functions over time, to assess which factors may influence
the cognitive decline in DM. In this perspective, we showed in this
study that Trail Making Test B was the test the most associated with
blood pressure, and thereby should be part of the cognitive
evaluation.
Disclosure of interest
The authors declare that they have no conflicts of interest concerning
this article.
References
[1] Nathan DM. Long-term complications of diabetes mellitus. N Engl J
Med 1993;328:1676-85.
[2] Nooyens AC, Baan CA, Spijkerman AM, Verschuren WM. Type 2 diabetes
and cognitive decline in middle-aged men and women: the Doetinchem
Cohort Study. Diabetes Care 2010;33:1964-9.
[3] Pasquier F, Boulogne A, Leys D, Fontaine P. Diabetes mellitus and
dementia. Diabetes Metab 2006;32:403-14.
[4] McCrimmon RJ, Ryan CM, Frier BM. Diabetes and cognitive
dysfunction. Lancet 2012;379:2291-9.
[5] Pasquier F. Diabetes and cognitive impairment: how to evaluate the
cognitive status? Diabetes Metab 2010;36:S100-5.
[6] Alvarez JA, Emory E. Executive function and the frontal lobes: a
meta-analytic review. Neuropsychol Rev 2006;16:17-42.
[7] Jones DT. Neural networks, cognition, and diabetes: what is the
connection? Diabetes 2012;61:1653-5.
[8] Artola A, Kamal A, Ramakers GM, Gardoni F, Di Luca M, Biessels GJ,
et al. Synaptic plasticity in the diabetic brain: advanced aging? Prog
Brain Res 2002;138:305-14.
[9] King GL, Loeken MR. Hyperglycemia-induced oxidative stress in
diabetic complications. Histochem Cell Biol 2004;122:333-8.
[10] Bourdel-Marchasson I, Mouries A, Helmer C. Hyperglycaemia,
microangiopathy, diabetes and dementia risk. Diabetes Metab
2010;36:70477-8.
[11] Ottenbacher KJ, Ostir GV, Peek MK, Markides KS. Diabetes mellitus
as a risk factor for stroke incidence and mortality in Mexican
American older adults. J Gerontol A Biol Sci Med Sci 2004;59:M640-5.
[12] Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM.
Diabetes mellitus and the risk of dementia: The Rotterdam Study.
Neurology 1999;53:1937-42.
[13] de Galan BE, Zoungas S, Chalmers J, Anderson C, Dufouil C, Pillai
A, et al. Cognitive function and risks of cardiovascular disease and
hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes
and Vascular Disease: Preterax and Diamicron Modified Release
Controlled Evaluation (ADVANCE) trial. Diabetologia 2009;52:2328-36.
[14] Bauduceau B, Doucet J, Bordier L, Garcia C, Dupuy O, Mayaudon H.
Hypoglycaemia and dementia in diabetic patients. Diabetes Metab
2010;36:70476-6.
[15] Dumurgier J, Paquet C, Peoc'h K, Lapalus P, Mouton-Liger F,
Benisty S, et al. CSF Abeta1-42 levels and glucose metabolism in
Alzheimer's disease. J Alzheimers Dis 2011;27:845-51.
[16] Bourdel-Marchasson I, Lapre E, Laksir H, Puget E. Insulin
resistance, diabetes and cognitive function: consequences for
preventative strategies. Diabetes Metab 2010;36:173-81.
[17] Novak V, Hajjar I. The relationship between blood pressure and
cognitive function. Nat Rev Cardiol 2010;7:686-98.
[18] Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife
cardiovascular risk factors and risk of dementia in late life.
Neurology 2005;64:277-81.
[19] Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of
blood pressure to cognitive function and dementia. Lancet Neurol
2005;4:487-99.
[20] Tarnow L, Rossing P, Gall MA, Nielsen FS, Parving HH. Prevalence
of arterial hypertension in diabetic patients before and after the
JNC-V. Diabetes Care 1994;17:1247-51.
[21] Reijmer YD, van den Berg E, Ruis C, Kappelle LJ, Biessels GJ.
Cognitive dysfunction in patients with type 2 diabetes. Diabetes Metab
Res Rev 2010;26:507-19.
[22] Brands AM, Van den Berg E, Manschot SM, Biessels GJ, Kappelle LJ,
De Haan EH, et al. A detailed profile of cognitive dysfunction and its
relation to psychological distress in patients with type 2 diabetes
mellitus. J Int Neuropsychol Soc 2007;13:288-97.
[23] Ding J, Strachan MW, Reynolds RM, Frier BM, Deary IJ, Fowkes FG,
et al. Diabetic retinopathy and cognitive decline in older people with
type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes
2010;59:2883-9.
[24] Bruce DG, Davis WA, Casey GP, Starkstein SE, Clarnette RM,
Almeida OP, et al. Predictors of cognitive decline in older
individuals with diabetes. Diabetes Care 2008;31:2103-7.
[25] Hatzitolios AI, Didangelos TP, Zantidis AT, Tziomalos K,
Giannakoulas GA, Karamitsos DT. Diabetes mellitus and cerebrovascular
disease: which are the actual data? J Diabetes Complications
2009;23:283-96.
[26] van Harten B, de Leeuw FE, Weinstein HC, Scheltens P, Biessels
GJ. Brain imaging in patients with diabetes: a systematic review.
Diabetes Care 2006;29:2539-48.
[27] Reijmer YD, Brundel M, de Bresser J, Kappelle LJ, Leemans A,
Biessels GJ. Microstructural White Matter Abnormalities and Cognitive
Functioning in Type 2 Diabetes: A diffusion tensor imaging study.
Diabetes Care 2012;6:6.
[28] Manschot SM, Biessels GJ, de Valk H, Algra A, Rutten GE, van der
Grond J, et al. Metabolic and vascular determinants of impaired
cognitive performance and abnormalities on brain magnetic resonance
imaging in patients with type 2 diabetes. Diabetologia
2007;50:2388-97.
[29] Vamos EP, Harris M, Millett C, Pape UJ, Khunti K, Curcin V, et
al. Association of systolic and diastolic blood pressure and all cause
mortality in people with newly diagnosed type 2 diabetes:
retrospective cohort study. Bmj 2012;30.
[30] Bots ML, Witteman JC, Hofman A, de Jong PT, Grobbee DE. Low
diastolic blood pressure and atherosclerosis in elderly subjects. The
Rotterdam study. Arch Intern Med 1996;156:843-8.
[31] Cholerton B, Baker LD, Craft S. Insulin resistance and
pathological brain ageing. Diabet Med 2011;28:1463-75.
[32] Qiu C, von Strauss E, Fastbom J, Winblad B, Fratiglioni L. Low
blood pressure and risk of dementia in the Kungsholmen project: a
6-year follow-up study. Arch Neurol 2003;60:223-8.
[33] Rucker JL, McDowd JM, Kluding PM. Executive function and type 2
diabetes: putting the pieces together. Phys Ther 2012;92:454-62.
[34] van der Meer JB, Mackenbach JP. The care and course of diabetes:
differences according to level of education. Health Policy
1999;46:127-41.
[35] Dray-Spira R, Gary TL, Brancati FL. Socioeconomic position and
cardiovascular disease in adults with and without diabetes: United
States trends, 1997-2005. J Gen Intern Med 2008;23:1634-41.
[36] Dray-Spira R, Gary-Webb TL, Brancati FL. Educational disparities
in mortality among adults with diabetes in the U.S. Diabetes Care
2010;33:1200-5.
[37] Dumurgier J, Paquet C, Benisty S, Kiffel C, Lidy C, Mouton-Liger
F, et al. Inverse association between CSF Abeta 42 levels and years of
education in mild form of Alzheimer's disease: the cognitive reserve
theory. Neurobiol Dis 2010;40:456-9.
[38] Osher E, Stern N. Diastolic pressure in type 2 diabetes: can
target systolic pressure be reached without "diastolic hypotension"?
Diabetes Care 2008;31:S249-54.
[39] Bourdel Marchasson I, Doucet J, Bauduceau B, Berrut G, Blickle
JF, Brocker P, et al. Key priorities in managing glucose control in
older people with diabetes. J Nutr Health Aging 2009;13:685-91.
[40] Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E,
Nauck M, et al. Management of hyperglycaemia in type 2 diabetes: a
patient-centered approach. Position statement of the American Diabetes
Association (ADA) and the European Association for the Study of
Diabetes (EASD). Diabetologia 2012;55:1577-96.

Table 1. Characteristics of the study sample.
Characteristics
N=32
Clinical characteristics
Age, years, median (25,75 percentile)
73.3 (68.6 – 78.5)
Women, n
7
Education level, n*
Low
13
Medium
8
High
11
Body mass index, kg/m2, median (25,75 percentile)
27.2 (25.4 – 31.5)
Systolic blood pressure, mmHg, median (25,75 percentile)
131.5 (120.0 – 149.5)
Diastolic blood pressure, mmHg, median (25,75 percentile)
67.5 (61.0 – 76.0)
Pulse pressure, mmHg, median (25,75 percentile)
69.0 (51.0 – 75.5)
Hypertension, n
24
Stroke history, n
5
Use of psychotropic drugs, n
5
Diabetes characteristics
Duration of the disease, years, median (25,75 percentile)
21.0 (11.0 – 30.5)
Oral hypoglycaemic agents (OHA), n
17
Insulin therapy, n
10
Combined OHA and insulin, n
5
Antihypertensive drugs, n
25
Lipid lowering drugs, n
23
Glycated hemoglobin, %, median (25,75 percentile)
7.20 (6.75 – 7.85)
Fasting glycemia, mmol/L, median (25,75 percentile)
1.44 (1.07 – 1.74)
Cognitive evaluation
MMSE score, median (25,75 percentile)
27.0 (24.5 – 28.5)
Frontal Assesment Battery, median (25,75 percentile)
14.5 (12.0 – 16.5)
Trail Making Test A, seconds, median (25,75 percentile)
65.5 (50.0 – 90.0)
Trail Making Test B, seconds, median (25,75 percentile)
203 (132 – 310)
QPC, median (25,75 percentile)
1.0 (0 – 1.5)
Memory Impairment Screen, mean (SD), range
8.0 (7.0 – 8.0)
CESD-scale, median (25,75 percentile)
11.0 (6.0 – 14.5)
Finger Tapping Test, median (25,75 percentile)
38.0 (32.0 – 43.5)
Verbal fluency, median (25,75 percentile)
24.0 (17.0 – 28.0)
MMSE: Mini Mental State Examination; QPC: questionnaire of cognitive
complaints;
CESD: Center for Epidemiologic Studies Depression.
*Low: no school or primary level; Medium: secondary level; High:
baccalaureate or university degree
Table 2. Spearman’s rank correlation coefficients between cognitive
tests and blood pressure.
Systolic blood pressure
Diastolic blood pressure
Pulse pressure
Cognitive test
ρ
P-value
ρ
P-value
ρ
P-value
MMSE
0.30 (-0.06, 0.59)
0.10
0.32 (-0.03, 0.61)
0.07
0.16 (-0.20, 0.49)
0.38
Frontal assesment battery
0.15 (-0.21, 0.48)
0.41
0.42 (0.08, 0.67)
0.02
-0.04 (-0.38, 0.31)
0.86
Trail Making Test A
0.17 (-0.20, 0.53)
0.36
-0.26 (-0.57, 0.11)
0.17
0.39 (0.05, 0.64)
0.03
Trail Making Test B
-0.03 (-0.38, 0.33)
0.89
-0.51 (-0.73, -0.19)
0.003
0.25 (-0.12, 0.55)
0.18
Q3PC
0.13 (-0.23, 0.46)
0.49
-0.20 (-0.51, 0.16)
0.28
0.30 (-0.05, 0.59)
0.09
Memory Impairment Screen
0.34 (-0.02, 0.62)
0.06
0.23 (-0.14, 0.54)
0.22
0.23 (-0.13, 0.54)
0.21
CESD-scale
-0.10 (-0.43, 0.26)
0.60
-0.26 (-0.56, 0.10)
0.15
0.12 (-0.22, 0.45)
0.50
Finger Tapping Test
-0.05 (-0.39, 0.30)
0.77
0.36 (0.01, 0.63)
0.046
-0.24 (-0.54, 0.07)
0.19
Verbal fluency
-0.07 (-0.42, 0.29)
0.69
0.36 (0.1, 0.63)
0.047
-0.23 (-0.53, 0.08)
0.21
MMSE: Mini Mental State Examination; QPC: questionnaire of cognitive
complaints; CESD: Center for Epidemiologic Studies Depression.
Table 3. Relationship between diastolic blood pressure and cognitive
function: linear regression models.
Frontal Assessment Battery
Trail Making Test B
Covariates
β(SE)
P value
Delta (%)
β(SE)
P value
Delta (%)
Unadjusted
0.38 (0.17)
0.029
Ref.
-0.49 (0.16)
0.005
Ref.
Age and sex
0.36 (0.16)
0.033
5.3
-0.44 (0.17)
0.01
10.2
Hypertensive drugs
0.37 (0.16)
0.026
2.6
-0.51 (0.15)
0.002
4.1
Body mass index
0.39 (0.17)
0.027
2.6
-0.53 (0.16)
0.002
8.1
Depressive symptoms
0.35 (0.17)
0.046
7.9
-0.44 (0.17)
0.01
10.2
Duration of the diabetes
0.37 (0.17)
0.042
2.6
-0.48 (0.17)
0.01
2.0
Glycated hemoglobin
0.39 (0.17)
0.035
2.6
-0.48 (0.17)
0.06
2.0
Education level
0.22 (0.19)
0.25
42.1
-0.35 (0.19)
0.08
28.6
β: standardized regression coefficients. SE: standard error.
Table 4. Relationship between education level, blood pressure and
cognition.
Education level
Characteristics
Low
Medium
High
P for trend
Systolic blood pressure, mmHg, mean (SD)
127.5 (15.3)
137.9 (20.3)
137.4 (19.5)
0.18
Diastolic blood pressure, mmHg, mean (SD)
63.2 (9.6)
68.6 (9.7)
73.5 (7.9)
0.008
Frontal Assessment Battery, mean (SD)
12.8 (2.5)
14.6 (2.1)
15.5 (2.4)
0.007
Trail Making Test B, mean (SD)
297.2 (113.4)
209.6 (89.0)
148.2 (109.6)
0.002
Figure legend
Figure 1. Scatter plots of diastolic blood pressure in function of
Frontal Assessment Battery (A), Trail Making Test B (B), Finger
Tapping Test (C), and Verbal Fluency (D). Linear regression lines are
represented.
16