Marie-Laure Seux

Relationship Between Arterial Stiffness and Cognitive Function in Elderly Subjects With Complaints of Memory Loss

Background and Purpose— To evaluate the relationship between arterial stiffness and cognitive function in a population of elderly subjects reporting memory loss. Methods— We studied the association between cognitive function and arterial stiffness in 308 consecutive elderly subjects attending a geriatric outpatient clinic reporting memory impairment. Subjects were classified into 4 categories according to neuropsychological evaluation: normal cognitive function, mild cognitive impairment (MCI), Alzheimer disease (AD), or vascular dementia (VaD). Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV) measurement using Complior. Results— In this population, 78±8 years of age (women 64%), AD was present in 41%, VaD in 6%, MCI in 27%, and 26% of subjects had normal cognitive function. After adjustment for age, gender, systolic blood pressure, education level, cardiovascular diseases, and antihypertensive therapy, a significant association was observed between PWV and cognitive status (P<0.0001). PWV appears significantly higher in subjects with VaD (15.2±3.9 m/s) or AD (13.3±2.9 m/s) than in those without cognitive impairment (11.5±2.0 m/s; P<0.001). Moreover, PWV was higher in subjects with MCI (12.6±2.6 m/s) than in those without cognitive impairment (11.5±2.0 m/s; P=0.01). For each 2 m/s increment in PWV, the adjusted odds ratio (95% CI) was 1.73 (1.27 to 2.47) for AD and 3.52 (1.87 to 8.05) for VaD. Conclusion— Our results showed a relationship between arterial stiffness and cognitive impairment, suggesting that functional changes of the arterial system could be involved in the onset of dementia (VaD or AD types).

Correlates of cognitive status of old patients with isolated systolic hypertension: the Syst-Eur Vascular Dementia Project

Objective To assess cognitive functions and their correlates for a dementia-free cohort of old patients with isolated systolic hypertension. Design Cross-sectional data from the randomization period of the European Trial in Elderly with Systolic Hypertension (Syst-Eur Vascular Dementia Project). Setting Sixteen European countries and Israel. Participants We studied 2252 patients aged 60–100 years (mean 70). Main outcome measures Mini Mental State Examination (MMSE) and Spearman correlation of MMSE scores to demographic data or blood pressure. Results The MMSE was successfully completed for 1474 women and 751 men. The baseline blood pressure averaged 173 ± 10/86 ± 6 mmHg (means ± SD). Median age at which education of patients at school had stopped was 15 years. Men and women who consumed alcohol (28%) had median intakes of 8 and 3 g/day, respectively. The median MMSE score was 29 (range 15–30). The maximum score of 30 was attained by 609 (30%) subjects. Fifty-nine (3%) patients had a MMSE score of 23 or less. The MMSE score decreased with advancing age (r = −0.21, P < 0.001). Both for men and for women, it was positively correlated to the level of education (r = 0.30 and r = 0.32, P < 0.001). For women after adjustment for age and the level of education, the score was correlated negatively to systolic blood pressure (r = −0.07, P < 0.05) but positively to intake of alcohol (r = 0.06, P < 0.05). Conclusion In a cohort of elderly patients with isolated systolic hypertension, baseline cognitive function measured in terms of the MMSE score was high, probably due to selective recruitment of patients who were not clinically demented. Blood pressure was a weak contributor to cognitive status compared with age and level of education. Baseline cognitive function of women was negatively and independently correlated to systolic blood pressure.

Calcium Channel Blockade and Cardiovascular Prognosis in the European Trial on Isolated Systolic Hypertension

In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications. Age at randomization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 23.4 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P</=0. 01) in total mortality (40%), stroke (59%), and all cardiovascular end points (39%). Among the control patients, 863 used only the first-line placebo. Compared with this subgroup, patients receiving monotherapy with nitrendipine showed a nearly 50% (P</=0.004) reduction of all types of end points, including total and cardiovascular mortality. The full relative benefit from nitrendipine was seen as early as 6 months after randomization. To ascertain that the benefit conferred by the dihydropyridine was not due to selection bias, the 1327 patients remaining on monotherapy with nitrendipine were matched by gender, age, previous cardiovascular complications, and systolic blood pressure at entry with an equal number of placebo patients. In this analysis, nitrendipine reduced (P</=0.05) cardiovascular mortality by 41%, all cardiovascular end points by 33%, and fatal and nonfatal cardiac end points by 33%. Despite the limitations inherent in post hoc analyses, the present findings suggest that the calcium channel blocker nitrendipine, given as a single antihypertensive medication, prevents cardiovascular complications in older patients with isolated systolic hypertension.

Systolic Hypertension in Europe (Syst-Eur) Trial Phase 2: objectives, protocol, and initial progress

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (⩾60 years) patients with isolated systolic hypertension (systolic BP ⩾160 mm Hg and diastolic BP <95 mm hg). after the completion of the syst-eur trial on 14 february 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the syst-eur trial. this open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. to lower the sitting systolic bp below 150 mm hg (target bp), the first-line agent nitrendipine (10–40 mg/day) may be associated with enalapril (5–20 mg/day), hydrochlorothiazide (12.5–25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. on 1 november 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. the median follow-up in syst-eur 2 was 14.3 months. at the last available visit, systolic/diastolic bp in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Cl: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm hg diastolic (95% cl: 0.4 to 1.5 mm mm hg; P < 0.001). at the beginning of syst-eur 2, the goal bp was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. at that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. until the end of 2001, bp control of the syst-eur 2 patients will be further improved. cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.

L’aide aux personnes souffrant de maladie d’Alzheimer et à leurs aidants par les gérontechnologies

The increasing number of people suffering from Alzheimers disease raises the question of their caring at home, especially when the disease causes disability and negative consequences in daily life such as isolation, falls, wandering, errors in drug taking. Furthermore, caregivers bear a substantial burden that can have adverse effects on their physical and mental health. New technologies of information could play an additional role as care providers without substituting family or professional caregivers help. A review of literature focused on the different technological solutions conceived for patients suffering from Alzheimers disease and their carers shows that these appliances could help to provide reminders in daily life (drugs, tasks and appointments, meals cooking), to activate residual cognitive resources by computerized cognitive stimulation intervention, to reduce stress, anxiety and depressive symptoms in patients by visual contact with families and professionals (webconference), to contribute to patients safety by detecting falls and wandering, and to help families in the caring of patients with computerized information and counselling interventions. We also discuss the current limitations for a widespread use of these technologies and outline future research avenues. True needs of end-users are still poorly known and should be more clearly defined. Simplicity of the use of these appliances should be further improved. Demonstration of medical and social benefits for elderly people should be carried out in randomized, controlled studies. Ethical reflexion should be developed in conjunction with the use of these gerontechnologies. Finally, the economical model which would enable the providing of these appliances to the largest number of patients and caregivers should be implemented. Although these gerontechnologies are promising, research is still needed to tailor them properly to the needs of end-users, assess their benefit in ecological context of people with Alzheimers disease in order to provide them with appropriate tools in daily life.

Home blood pressure measurement in elderly patients with cognitive impairment: comparison of agreement between relative-measured blood pressure and automated blood pressure measurement.

ObjectivesHome blood pressure measurement (HBPM) is recommended by guidelines for hypertension management. However, this method might be difficult to use in elderly individuals with cognitive disorders. Our aim was to assess the agreement and the feasibility of HBPM by a relative as compared with 24-h ambulatory blood pressure monitoring (ABPM) in elderly patients with dementia. MethodsSixty outpatients with dementia aged 75 years and older with office hypertension (≥140/90 mmHg) were subjected successively to HBPM by a trained relative and 24-h ABPM. The order of the two methods was randomized. Current guidelines’ thresholds for the diagnosis of hypertension were used. ResultsThe mean (SD) age of the patients was 80.8 (6.1) years (55% women) and the mean (SD) mini-mental state examination score was 20.1 (6.9). The feasibility of relative-HBPM was very high, with a 97% success rate (defined by ≥12/18 measurements reported). The blood pressure measurements were highly correlated between the two methods (r=0.75 and 0.64 for systolic blood pressure and diastolic blood pressure, respectively; P<0.001 for both). The agreement between the methods for the diagnosis of sustained hypertension and white-coat hypertension was excellent (overall agreement, 92%; &kgr; coefficient, 0.81; 95% CI, 0.61–0.93). Similar results were found for daytime-ABPM. ConclusionIn cognitively impaired elderly patients, HBPM by a relative using an automated device was a good alternative to 24-h ABPM.

Low Serum Insulin-Like Growth Factor-I Predicts Cognitive Decline in Alzheimer’s Disease

BACKGROUND The relationship between the insulin-like growth factor-I (IGF-I) system and Alzheimers disease (AD) is mostly based on transversal studies. It remains, however, to demonstrate whether IGF-I is associated with cognitive decline over time in AD. OBJECTIVE The objective of the study was to analyze the course of cognitive decline of AD subjects over a 24-month period in relation to serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) measured at baseline. METHODS Data are from the SIGAL follow-up study. IGF-I and IGFBP-3 were measured in AD subjects who performed a Mini-Mental State Examination (MMSE) every 6 months for 2 years. MMSE course was analyzed using a mixed model with random intercept and slope function. RESULTS Among the 200 AD participants, 146 (mean age = 81.1 (standard deviation (SD) = 5.9) years, 62.6% of women) had at least one follow-up visit. Mean IGF-I at baseline was 147.8 (74.2) ng/mL. Hundred forty-six participants (62.6%) had at least one follow-up visit. Mean MMSE was 21.7 (4.7)/30 and dropped on average by 2.28 points per year. MMSE decline was steeper among participants with lower IGF-I. For each decrease of 1 SD of IGF-I, subjects lost an additional 0.63 points per year in MMSE, e.g., participants with IGF-I level of 74 ng/mL lost 2.91 MMSE points per year whereas participants with IGF-I of 222 ng/mL lost 1.65 MMSE points per year. There was no association between IGFBP-3 and cognitive decline. CONCLUSION Lower baseline serum IGF-I was associated with faster cognitive decline in AD over a 2-year period.

Relationships between personality traits, medial temporal lobe atrophy, and white matter lesion in subjects suffering from mild cognitive impairment

Mild cognitive impairment (MCI) is a heterogeneous cognitive status that can be a prodromal stage of Alzheimer’s disease (AD). It is particularly relevant to focus on prodromal stages of AD such as MCI, because patho-physiological abnormalities of AD start years before the dementia stage. Medial temporal lobe (MTL) atrophy resulting from AD lesions and cerebrovascular lesions [i.e., white matter lesions (WML), lacunar strokes, and strokes] are often revealed concurrently on magnetic resonance imaging (MRI) in MCI subjects. Personality changes have been reported to be associated with MCI status and early AD. More specifically, an increase in neuroticism and a decrease in conscientiousness have been reported, suggesting that higher and lower scores, respectively, in neuroticism and conscientiousness are associated with an increased risk of developing the disease. However, personality changes have not been studied concomitantly with pathological structural brain alterations detected on MRI in patients suffering from MCI. Therefore, the objective of the present study was to assess the relationship between MTL atrophy, WML, lacunar strokes, and personality traits in such patients. The severity of WML was strongly associated with lower levels of conscientiousness and higher levels of neuroticism. Conversely, no association was detected between personality traits and the presence of lacunar strokes or MTL atrophy. Altogether, these results strongly suggest that personality changes occurring in a MCI population, at high risk of AD, are associated with WML, which can induce executive dysfunctions, rather than with MTL atrophy.

Insulin-Like Growth Factor I, Insulin-like Growth factor Binding Protein 3, and Atrial Fibrillation in the Elderly

BACKGROUND Insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) are involved in oxidative stress and atherosclerosis; however, the relationship between the IGF-I system and atrial fibrillation (AF) is not known. The objective of this analysis was to assess, the relationship between IGF-I and IGFBP-3 serum levels and AF among elderly participants. METHODS In this cross-sectional study, 719 participants (mean age [SD] years: 78.2 [6.8]; 31.8% men) were evaluated during an outpatient geriatric assessment. AF was determined by electrocardiogram or medical record. Participants were classified into two groups: Participants with AF (n = 91) or without AF (n = 628). IGF-I and IGFBP-3 serum levels were determined by enzyme linked immunosorbent assay. RESULTS After adjusting for age and sex, the mean IGF-I and IGFBP-3 serum levels were significantly lower among AF participants than among non-AF participants (mean IGF-I ng/mL [SD] = 133.8 [66.6] vs 157.9 [80.0], p = .02; mean IGFBP-3 ng/mL [SD] = 3,653 [1,393] vs 4,151 [1,583], p = .03, respectively). After adjusting for confounding factors (age, gender, beta blocker medication, heart rate, hypertension, stroke, and chronic heart failure), low IGF-I serum level (OR [95% CI] = 0.66 [0.49-0.87]) and low IGFBP-3 serum level (0.71 [0.54-0.93]) remained independent determinants of AF. CONCLUSIONS Low IGF-I and low IGFBP-3 serum levels were independently associated with AF in this elderly population. This result should be confirmed in a longitudinal study to evaluate whether IGF-I and/or IGFBP-3 serum levels are predictive of incident AF.

Diuretics for cardiovascular prevention in the elderly.

High blood pressure (BP) is a major risk factor for cardiovascular and cerebrovascular diseases in elderly subjects. Antihypertensive drugs have shown clinical benefit both in primary and secondary prevention of cardiovascular events. If BP lowering represents the major determinant of the effects conferred by the antihypertensive treatment for prevention, recent studies have suggested some differences between classes of antihypertensive drugs according to age. Based on the available clinical data, the recent medical guidelines have recommended thiazide-type diuretics as the preferred drug for the treatment of elderly hypertensive patients, followed by long-acting calcium antagonists. Indeed, diuretics constitute one of the most valuable classes of antihypertensive drugs, and in the elderly, diuretic-based treatment studies have been clearly shown to prevent major cardiovascular events, including stroke, heart failure and coronary heart disease.