Feasibility and Determinants of Orthostatic Hypotension Self-measurement at Home in an Elderly Community-Dwelling Population.

BACKGROUND: Orthostatic hypotension (OH) measurement reproducibility is poor. Our objectives were to assess feasibility of self-detection home-measured OH (HOH) and HOH determinants. METHODS: Subjects older than 65 years, attending a geriatric outpatient clinic, able to understand the HOH protocol: 3 blood pressure (BP) measures after 5 minutes of seating and BP measures after 1 and 3 minutes of standing, each morning and evening for 3 consecutive days were lent a validated digital automatic sphygmomanometer. Reports containing at least 4 correct measurements were deemed a success. Factors associated with HOH were studied. RESULTS: HOH feasibility was 82.8% (241 subjects) with no difference between participants who failed or succeeded. Among the 241 subjects (mean age (SD) = 78.0 (8.3) years old; 62.1% of women), 139 were free of HOH, 70 had 1 HOH episode and 32 had 2 or more HOH episodes. Hypertension, dementia, atrial fibrillation, diabetes, and heart failure were found in 70.0%, 10.4%, 9.4%, 8.8%, and 3.4% of cases, respectively. Subjects were treated with antihypertensive, benzodiazepine, statin medication in 47.3%, 9.3%, 7.4% of cases, respectively, and 42.4% experienced polypharmacy. HOH episodes were associated with dementia (P = 0.01), presence of OH during the geriatric outpatient clinic assessment (P = 0.0002), statin therapy (P = 0.04), and polypharmacy (P = 0.0002). In multivariate analysis, benzodiazepine (OR (95% CI) = 2.59 (1.10-6.08) and statin medication (OR (95% CI) = 1.92 (1.10-3.33)) remained significantly associated with HOH. CONCLUSIONS: HOH had a good feasibility and relevant determinants. A study to address the predictive value of HOH will be conducted.

Pulse Wave Velocity Is Associated With Greater Risk of Dementia in Mild Cognitive Impairment Patients.

To investigate the association between pulse wave velocity, intima-media thickness, carotid artery diameter, carotid plaques, and conversion from mild cognitive impairment to dementia. Three hundred and seventy-five elderly ambulatory subjects with mild cognitive impairment were followed yearly to examine potential conversion to dementia. Vascular function was assessed by carotid-femoral pulse wave velocity. Vascular structure was evaluated by intima-media thickness, carotid artery diameter, and carotid plaques using an ultrasonographic assessment of carotid arteries. One hundred and five patients (28%) converted to dementia during a mean follow-up period of 4.5 years. Higher pulse wave velocity was associated with greater risk of conversion to dementia (1-SD increase of pulse wave velocity: hazard ratio, 1.33; 95% CI, 1.04-1.71; P=0.02) independently of age, sex, educational level, systolic blood pressure, cardiovascular diseases, body mass index, calcium channel blockers intake, Mini-Mental State Examination at baseline, and apoE ε4 status. Intima-media thickness, carotid plaques, and carotid artery diameter did not predict conversion to dementia (1-SD increase of intima-media thickness: hazard ratio, 0.93; 95% CI, 0.73-1.18; P=0.55; presence of carotid plaques: hazard ratio, 1.08; 95% CI, 0.62-1.87; P=0.79; 1-SD increase of carotid artery diameter: hazard ratio, 1.08; 95% CI, 0.89-1.31; P=0.44). Pulse wave velocity was associated with conversion to dementia, whereas intima-media thickness, carotid plaques, or carotid artery diameter were not after controlling for age and other confounding factors. Arterial stiffness could identify mild cognitive impairment patients at higher risk of dementia and may be a therapeutic target to delay or prevent the onset of dementia.

Do informal caregivers of demented patients refuse clinic comprehensive medico-psycho-social assessment? Prevalence and reasons for refusal.

OBJECTIVE: Caregivers do not usually use services that could alleviate their burden. The objectives were to determine the refusal's prevalence and the reasons why informal caregivers of demented patients refuse clinic medico-psycho-social assessment in the first day care hospital dedicated to caregivers in France. METHODS: Caregivers of patients hospitalized in geriatric ward were prospectively asked to fill in a questionnaire (demographic data, risk for depression and caregiver burden (Zarit scale) about their willingness to benefit from a clinic checkup. If caregivers refused eleven close questions were asked. Characteristics of the caregivers were compared according to the caregivers' agreement or refusal to the clinic checkup. RESULTS: Seventy-seven caregivers (mean age (standard deviation): 68.2 (11.5)) were included: 68.8% of women, 51.9% of children and 35.1% of spouses, mean Zarit scale score was 32.8 (8.8)/88. Clinic checkup was accepted by 28 caregivers. Agreement was associated with exhaustion (p<0.001), depression (p=0.003), memory complaints (p<0.001) and higher burden (p=0.008). Reasons for refusal were mostly the belief that support was sufficient (67.3%) and good self-perceived health (44.9%). Nearly 1/4 of caregivers though that the clinic checkup would be useless. CONCLUSION: Two third of caregivers refused the evaluation because subjective feeling of good physiological and psychological health and that currently provided support was sufficient. Studies to address caregivers 'needs should be conducted.

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 Alzheimer's 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.

[DAD-6: an abbreviated version of the DAD scale (disability assessment for dementia). An instrument for detection of loss of autonomy at an early stage]. / DAD-6 : version abrégée de la DAD (disability assessment for dementia) Outil de détection d'une perte d'autonomie précoce.

This paper presents the French version of DAD-6, a validated instrument for the assessment of IADL (instrumental activities of daily living) considered as intentional and complex activities. A loss of autonomy remains a major criterion in the diagnosis of dementia. In addition, IADL assessment is recommended as a primary outcome in dementia drug trials. Since the publication in 1969 by Lawton and Brody of an IADL scale, many instruments have been developed. However, their psychometric properties remain to be improved. The need for improving the early diagnosis yielded to the design of DAD-6, an instrument allowing capturing subtle difficulties in IADL management. The DAD-6 scale emphasizes the role of the cognitive function, mainly the executive function in early IADL impairment. DAD-6 requires the participation of an informant (a patient's proxy). Relative to patients' self-reports or performance-based methods, informant-based questionnaires are the most common and practical methods used in memory clinics. In previous work, DAD-6 score gradually decreased with increasing severity of the cognitive status. The present work shows the inter-rater reliability of DAD-6. The use of the scale with the same informants by one neurologist and two neuropsychologists, separately, indicated a high agreement between raters (alpha of Krippendorff>0.80).This work also highlights the main sources of bias in the context of evaluation based on subjective judgement. The authors stress the necessity of: 1--a clarification of the relationship between cognitive function and IADL; 2--the measurement of IADL performance in a routine neuropsychological assessment by experienced professionals.

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.

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

OBJECTIVES: Home 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. METHODS: Sixty 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. RESULTS: The 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%; κ coefficient, 0.81; 95% CI, 0.61-0.93). Similar results were found for daytime-ABPM. CONCLUSION: In cognitively impaired elderly patients, HBPM by a relative using an automated device was a good alternative to 24-h ABPM.

[Support for patients with Alzheimer's disease and their caregivers by gerontechnology]. / L'aide aux personnes souffrant de maladie d'Alzheimer et à leurs aidants par les gérontechnologies.

The increasing number of people suffering from Alzheimer's 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 Alzheimer's 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 Alzheimer's disease in order to provide them with appropriate tools in daily life.

Effects of antihypertensive therapy on cognitive decline in Alzheimer's disease.

BACKGROUND: Therapeutic trials concerning the effect of antihypertensive therapy on cognition have produced controversial findings. Our objective was to evaluate the impact of antihypertensive therapy on the cognitive function in subjects already diagnosed with Alzheimer's disease (AD). METHODS: We conducted an observational study in a memory clinic assessing outpatients suffering from AD. A total of 321 patients were included. Cognitive function was assessed yearly by the Mini-Mental State Examination (MMSE; score/30). RESULTS: The mean age of patients was 78.1 +/- 6 years, 54% of them received antihypertensive therapy and the mean MMSE scores were similar in both groups (patients taking antihypertensive therapy and patient without antihypertensive therapy). The mean follow-up was 34.1 +/- 6 months. MMSE means were significantly higher among patients using antihypertensive therapy compared to those without antihypertensive therapy (MMSE scores = 21.9 +/- 4.9 vs. 21.2 +/- 5.1 at 1 year (P = 0.001); 20.8 +/- 5.5 vs. 19.4 +/- 5.7 at 2 years (P < 0.001); 19.0 +/- 6.7 vs. 17.5 +/- 6.4 at 3 years (P < 0.001)), after adjustment for age, gender, education level, systolic blood pressure (SBP), and diastolic blood pressure (DBP) at baseline, MMSE at baseline, coronary heart disease, statins, and antiplatelet agents' consumption. Furthermore, the use of antihypertensive therapy was associated with a lower estimated risk of cognitive decline (as defined by a decrease of at least one point in MMSE score over time) (hazard ratio = 0.61; 95% confidence interval = 0.45-0.81) after adjustment for the same factors. CONCLUSIONS: These results suggest an association between antihypertensive therapy, a lower decrease in mean MMSE and a lower cognitive decline over time in AD.

Apolipoprotein E epsilon4 allele frequency in elderly depressed patients with and without cerebrovascular disease.

Late-onset depression (LOD) could be a very early manifestation of Alzheimer's disease (AD), although contradictory results have been reported. Cerebrovascular disease (CVD) may favor the development of LOD, and that the particular forms of vascular depression should be individualized. The Apolipoprotein E (ApoE) epsilon4 allele was shown to be a risk factor for AD. Its role in LOD is controversial, while it is still unknown in vascular depression. Our objective was to clarify the relationship between ApoE epsilon4 allele and LOD in patients with and without CVD. We examined the ApoE phenotypes in a sample of 311 subjects: 50 with vascular LOD, 24 with LOD without CVD, 115 with AD and 122 normal controls (NC). The study of the ApoE epsilon4 allele frequency showed significant differences between: AD group and the vascular LOD and NC groups; LOD group without CVD compared with NC group (p<0.05 to 0.001). The frequency of the epsilon4 allele in the LOD group without CVD did not differ significantly from the AD group, similarly the frequency of the epsilon4 allele in the vascular LOD group was not different from that in NC. The study suggests an association between the ApoE epsilon4 allele and the LOD without CVD. These patients could be at risk of developing AD by an epsilon4-dependent pathway. In contrast, the results show no association between the presence of ApoE epsilon4 allele and vascular depression and provide further evidence in support of the concept that ApoE epsilon4 allele is not associated with clinical CVD.

Relationship between antihypertensive drug therapy and cognitive function in elderly hypertensive patients with memory complaints.

OBJECTIVE: To evaluate the relationship between antihypertensive treatments and cognitive function in elderly hypertensive patients with memory complaints. METHODS: The association between cognitive function and antihypertensive drug therapy was studied in 1241 hypertensive elderly patients with memory complaints attending a geriatric outpatient clinic. Cognitive function was assessed using the Mini Mental State Examination (MMSE) and validated neuropsychological tests (Cognitive Efficiency Profile; CEP). Patients were classified into four categories according to their cognitive status: normal cognitive function, mild cognitive impairment (MCI), Alzheimer's disease (AD) or vascular dementia (VaD). RESULTS: In this population aged 78 +/- 8 years, with a mean blood pressure of 152 +/- 19/86 +/- 12 mmHg, antihypertensive treatment was prescribed for 57% of patients. After adjustment for age, sex and education, treated hypertensive patients had better cognitive function than untreated patients (MMSE score 23.9 +/- 5.6/30 versus 22.7 +/- 6.4/30, P < 0.001, CEP score 49.1 +/- 24.9/100 versus 45.4 +/- 23.7/100, P < 0.001). This association was observed independently of the cognitive status, both in normal, MCI, AD and VaD hypertensive patients. The odds ratio (OR) for AD was 0.58 [95% confidence interval (CI) 0.42-0.81] in treated compared with untreated hypertensive patients. In patients on antihypertensive therapy, higher cognitive function was observed in patients using calcium antagonists compared with those without calcium antagonists (CEP 52.9 +/- 24.6/100 versus 46.4 +/- 23.4/100, P < 0.001; OR for AD 0.67; 95% CI 0.45-0.99), independently of blood pressure level. CONCLUSIONS: Antihypertensive therapy was associated with a lower risk of cognitive impairment and AD. In particular, the use of calcium antagonists was associated with a decreased risk of cognitive impairment and AD independently of the blood pressure level, suggesting a specific neuroprotective effect of these antihypertensive agents.

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. CONCLUSIONS: 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).

Initiation of warfarin therapy in elderly medical inpatients: a safe and accurate regimen.

PURPOSE: Elderly patients are at high risk of over-anticoagulation when treated with warfarin, especially during treatment induction. We developed a simple low-dose regimen for starting warfarin therapy in elderly inpatients. The daily maintenance dosage is predicted from the international normalized ratio (INR) measured the day after the third daily intake of a 4-mg dose. We conducted a prospective multicenter study to evaluate the accuracy and safety of this regimen. METHODS: We studied 106 elderly (age >or=70 years) inpatients (mean [+/- SD] age, 85 +/- 6 years; range, 71 to 97 years) who had a target INR of 2.0 to 3.0. Accuracy in predicting the daily maintenance dose from INR value on day 3 was evaluated. RESULTS: The predicted daily maintenance warfarin dose (3.1 +/- 1.6 mg/d) correlated closely with the actual maintenance dose (3.2 +/- 1.7 mg/d; R(2) = 0.84). The predicted dose was equal to the actual dose in 77 patients (73%; 95% confidence interval [CI]: 64% to 81%) and within 1 mg in 101 patients (95%; 95% CI: 91% to 99%). The mean time needed to achieve a therapeutic INR was 6.7 +/- 3.3 days (median, 6.0 days); the mean time needed to achieve the maintenance dose was 9.2 +/- 4.5 days (median, 7.0 days). None of the patients had an INR >4.0 during this period. One fatal bleeding event was recorded in a patient with an INR in the therapeutic range. CONCLUSION: Our warfarin induction regimen was simple, safe, and accurate in predicting the daily maintenance warfarin dose in elderly hospitalized patients.

Prevention of dementia and cerebroprotection with antihypertensive drugs.

High blood pressure is a major risk factor for stroke and is also closely correlated with cognitive decline and dementia. Indeed, most longitudinal studies showed that cognitive functioning is often inversely proportional to blood pressure values measured 15 or 20 years previously. Because of the aging of the population, the frequency of stroke and dementia will dramatically increase in the coming years. Therefore, the prevention of cerebrovascular and cognitive disorders represents a major challenge. Antihypertensive drugs have shown clinical benefits in both primary and secondary prevention of strokes. Consensus is generally that blood-pressure lowering represents the major determinant of the benefit conferred by the antihypertensive treatment for stroke prevention; however, recent studies have suggested some differences between classes of antihypertensive drugs. The results of therapeutic trials (Systolic Hypertension in Europe, Perindopril Protection Against Recurrent Stroke Study [PROGRESS]) open the way to the prevention of dementia (vascular or Alzheimer's type) by antihypertensive treatments. These two studies suggest different mechanisms for the prevention of cognitive decline using antihypertensive drugs. In this context, reduced incidence of dementia should be the primary outcome of future trials comparing different classes of antihypertensive drugs.

Hypertension and dementia.

Hypertension is one of the principal risk factors for cerebrovascular diseases. Several epidemiologic studies have also indicated a positive correlation between cognitive decline or dementia and blood pressure level. Indeed, the results of most longitudinal studies show that cognitive functioning is often inversely proportional to blood pressure values measured 15 or 20 years previously. Cerebral infarcts, lacunae, and white matter changes are implicated in the pathogenesis of vascular dementia, but may also favor the development of Alzheimer's disease. Microcirculation disorders and endothelial dysfunctions are also advanced to explain the deterioration in cognitive functions in hypertensive subjects. Data from recent therapeutic trials open the way to the prevention of dementia (vascular or Alzheimer's type) by antihypertensive treatments and must be confirmed by other studies.

The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study.

BACKGROUND: After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. OBJECTIVE: To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. METHODS: Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. RESULTS: Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P<.001). After adjustment for sex, age, education, and entry blood pressure, the relative hazard rate associated with the use of nitrendipine was 0.38 (95% confidence interval, 0.23-0.64; P<.001). Treatment of 1000 patients for 5 years can prevent 20 cases of dementia (95% confidence interval, 7-33). CONCLUSION: The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.

Antihypertensive drugs and cognitive function.

The increase in life expectancy is associated with a sharp rise in cognitive disorders, particularly after the age of 80 years. The identification and management of risk factors for these invalidating and distressing conditions must be considered a priority. Hypertension has been shown to carry an increased risk not only for cerebrovascular morbidity and mortality, but also for cognitive impairment and dementia. The fact that antihypertensive treatment has been demonstrated to decrease those risks offers a new opportunity to reduce the prevalence of such related disorders and to promote healthy aging.