Depression Increases the Risk of Death Independently From Vascular Events in Elderly Individuals: The Three-City Study.

BACKGROUND: How much the association between depressive symptoms (DSs) and all-cause mortality depends on cardiovascular disease (CVD) events is poorly known. We aimed to prospectively quantify the association between DSs at repeated study visits and all-cause and cause-specific mortality, and the influence of incident CVD on this association. METHODS: The Three-City Study has included adults 65 years and older, who were examined at baseline between 1999 and 2001 and after 2, 4, 7, and 10 years of follow-up. At each visit, a score of 16 or greater on the 20-item Center for Epidemiologic Studies Depression Scale defined the presence of DSs. DS status and incident coronary heart disease or stroke events were used as time-dependent variables in a Cox proportional hazard model of mortality. RESULTS: We studied 7377 participants (63.7% females) aged 73.8 years (SD = 5.4 years) without a history of CVD at baseline examination. DSs were present in 19% to 22% of subjects at each study visit. During a median follow-up of 9.4 years, 650 subjects developed a first CVD, and 1255 had died. After adjustment for baseline sociodemographic variables, vascular risk factors, impairment in daily life activities, and antidepressants, time-dependent DSs were associated with a 28% increased risk of mortality (hazard ratio [HR] = 1.28; 95% confidence interval [CI] = 1.06-1.55), and incident CVD event was associated with a 63% increased risk (HR = 1.63; 95% CI = 1.30-2.04). However, the association between DSs and mortality was not influenced by the occurrence of CVD (HR for DS and CVD interaction = 1.03; 95% CI = 0.66-1.61). A mediation analysis confirmed that incident CVD only explained 6.9% of the excess of mortality associated with DSs. CONCLUSION: In older participants, the increased risk of all-cause mortality associated with the presence of DSs at baseline and during follow-up is not modified by and is moderately mediated by incident CVD. J Am Geriatr Soc 67:546-552, 2019.

High Level of Depressive Symptoms at Repeated Study Visits and Risk of Coronary Heart Disease and Stroke over 10 Years in Older Adults: The Three-City Study.

BACKROUND: Baseline depressive symptoms have been consistently associated with the onset of cardiovascular disease (CVD). OBJECTIVES: Since depressive symptoms vary over time in elderly persons, and to help clarify whether or not depression is an etiological factor for CVD, we quantified the association between the course of depressive symptoms and occurrence of first coronary heart disease (CHD) and stroke events in older adults. DESIGN: A population-based prospective observational study. SETTING: Participants were randomly selected from the electoral rolls of three large French cities. PARTICIPANTS: A total of 9,294 participants were examined at baseline between 1999 and 2001, and thereafter at repeated study visits over 10 years. MEASUREMENTS: High levels of depressive symptoms (HLDS) were defined as a score≥16 on the 20-item Center for Epidemiologic Studies Depression Scale. The number of study visits with HLDS was used as a time dependent variable in Cox proportional hazard models. RESULTS: There were 7,313 participants (36.6% males) aged 73.8±5.4 years with no history of CHD, stroke or dementia at baseline. After a median follow-up of 8.4 years (SD 2.3 years), 629 first CHD or stroke events occurred. After adjustment for sociodemographic characteristics and vascular risk factors, the risk of CHD and stroke combined increased 1.15-fold (95% CI: 1.06 to 1.25) per each additional study visit with HLDS. The results remained unchanged when accounting for the presence of disability and antidepressant intake at baseline and during follow-up. CONCLUSION: Elderly persons exposed to HLDS at several occasions over 10 years showed substantial increased risk of coronary heart disease and stroke events.

Depressive symptoms, antidepressants and disability and future coronary heart disease and stroke events in older adults: the Three City Study.

To investigate the association between baseline depressive symptoms and first fatal and non fatal coronary heart disease (CHD) and stroke in older adults, taking antidepressants and disability into account. In the Three City Study, a community-based prospective multicentric observational study cohort, 7,308 non-institutionalized men and women aged ≥65 years with no reported history of CHD, stroke or dementia, completed the 20-item Center for Epidemiologic Studies depression scale (CESD) questionnaire. First CHD and stroke events during follow-up were adjudicated by an independent expert committee. Hazard ratios (HRs) were estimated by Cox proportional hazard model. After a median follow-up of 5.3 years, 338 subjects had suffered a first non-fatal CHD or stroke event, and 82 had died from a CHD or stroke. After adjustment for study center, baseline socio-demographic characteristics, and conventional risk factors, depressive symptoms (CESD ≥ 16) were associated with fatal events only: fatal CHD plus stroke (HR = 2.50; 95% CI 1.57-3.97), fatal CHD alone (n = 57; HR = 2.21 ; 95%CI 1.27-3.87), and fatal stroke alone (n = 25; HR = 3.27; 95% CI 1.42-7.52). These associations were even stronger in depressed subjects receiving antidepressants (HR = 4.17; 95% CI 1.84-9.46) and in depressed subjects with impaired Instrumental Activities of Daily Living (HR = 8.93; 95% CI 4.60-17.34). By contrast, there was no significant association with non fatal events (HR for non-fatal CHD or stroke = 0.94; 95% CI 0.66-1.33). In non-institutionalized elderly subjects without overt CHD, stroke or dementia, depressive symptoms were selectively and robustly associated with first fatal CHD or stroke events.

Comparison between the three most popular formulae to estimate renal function, in subjects 75 years of age or older.

OBJECTIVES: The aim of the study was to compare the accuracy of three formulae that estimate creatinine clearance (CL(CR)), in elderly hospitalized patients: the Cockcroft-Gault (CG) formula and the Modification of Diet in Renal Disease formulae with 4 and 6 variables (MDRD4 and MDRD6). METHODS: A prospective, cross-sectional, observational study was conducted in four hospital geriatric wards. Consecutive patients admitted to the wards who were aged ≥75 years and had an indwelling urinary catheter for the purpose of care were eligible for enrolment. CL(CR) was determined via four methods: measurement of CL(CR) from plasma and urine creatinine plus 24-h urine volume; the CG formula; and the MDRD4 and MDRD6 formulae. Moderate and severe renal impairments were defined as a CL(CR) of 30.0-59.9 and <30.0 mL/min, respectively. RESULTS: A total of 157 patients were included. Their mean age (±SD) was 86.5 ± 6.1 (range 75-105) years and 46.5 % were male. The median values and interquartile ranges (IQRs) (in mL/min) were 44.0 (IQR 32.1-64.5) for measured CL(CR), 42.1 (IQR 31.3-56.3) for CG-estimated CL(CR), 64.3 (IQR 49.8-81.7) for MDRD4-estimated CL(CR) and 49.3 (IQR 37.4-63.4) for MDRD6-estimated CL(CR) (respectively, p < 0.05, p < 0.001 and p = 0.44 compared with measured CL(CR)). Biases (±SD) for CG, MDRD4 and MDRD6 CL(CR) estimates were -3.6 (±22.2), 19.3 (±26.4) and 2.4 (±22.5) mL/min, respectively. When estimated CL(CR) values were assessed against the measured value, it was found that misclassification of renal impairment (absent/moderate/severe) occurred in 41 % of patients when using the CG, in 40 % when using the MDRD6, and in 45 % when using the MDRD4. The 30 % accuracies of the three formulae were 63 % for CG, 37 % for MDRD4 and 59 % for MDRD6. CONCLUSION: In elderly hospitalized patients, CG and MDRD6 gave better predictions for measured CL(CR) than MDRD4, with no significant difference between them.

Renal function in older hospital patients is more accurately estimated using the Cockcroft-Gault formula than the modification diet in renal disease formula.

OBJECTIVES: To compare the accuracy of the two most popular creatinine clearance (CrCl) estimation formulae (Cockcroft-Gault (CG) and Modification Diet in Renal Disease (MDRD)) in older hospitalized patients. DESIGN: Prospective, cross-sectional, observational study. SETTING: Two hospital geriatric wards. PARTICIPANTS: Consecutive patients aged 70 and older with an indwelling urinary catheter for the purpose of care. MEASUREMENTS: CrCl was determined according to three methods: measured CrCl from plasma and urine creatinine and 24-hour urine volume, CG (CG-CrCl), and MDRD (MDRD-CrCl). Results were expressed as median and interquartile range (IQR). Moderate and severe renal impairment were defined as a CrCl between 30.0 and 59.9 mL/min and less than 30.0 mL/min, respectively. RESULTS: One hundred twenty-one patients were included (46% male). Mean age was 86.1+/-6.7 (range 72-100). Median measured CrCl was 43.8 mL/min (IQR 33.6-61.1 mL/min), CG-CrCl was 40.9 mL/min (IQR 31.0-52.6 mL/min), and MDRD-CrCl was 61.3 mL/min (IQR 49.4-77.0 mL/min). The biases of CG-CrCl and MDRD were -3.5+/-22.5 and 20.1+/-28.2, respectively (P<.001). Misclassification of renal impairment (absent/moderate/severe) occurred in 33% of patients according to CG-CrCl, and concordance was mild to moderate (kappa=0.50). Misclassification occurred in 50% of patients according to MDRD-CrCl, and concordance was poor (kappa=0.33). Bias was significantly related to bed confinement for both formulae and to plasma creatinine for MDRD. CONCLUSION: In elderly hospitalized patients, CG slightly underestimates CrCl, and MDRD strongly overestimates it. CG gave a better prediction of measured CrCl than MDRD.

[Management of Alzheimer disease]. / Prise en charge de la maladie d'Alzheimer.

Management of Alzheimer disease is based on drug and nondrug treatments. Specific drug treatment includes acetylcholinesterase inhibitors and memantine. They show moderate efficacy superior to that of placebo for global condition, cognitive disorders, need for care, and behavioral problems, but do not prevent further decline. These treatments remain underused. The efficacy of psychotropic drugs (antidepressants, neuroleptics, and antipsychotic agents) in treating behavioral problems is not well documented. Nondrug activities and interventions have not been sufficiently evaluated scientifically. These involve interventions against the consequences of the disease (loss of autonomy, malnutrition) and helping patients' family caregivers. Among these activities, the best evaluated and most interesting are: educational programs for caregivers, occupational therapy at home, and interventions at home by nurses specially trained as case managers.

[Dementia syndromes in the elderly: diagnostic procedures]. / Syndromes démentiels du sujet âgé: démarches diagnostiques.

Dementia is a deterioration in several cognitive functions that affects daily living and is observed in the absence of impaired vigilance. Dementia may be revealed by symptoms of memory loss but also by a loss of functional autonomy, onset of depression or by behavioral problems; it may also be recognized during a screening examination. Evaluation of cognitive functions is an essential stage of this diagnosis. Simple tests that any physician can perform provide a first approach. A more detailed cognitive evaluation by a specialist or neuropsychologist is then necessary (except in advanced cases). Once dementia is diagnosed, a causal investigation is required to assess its severity and extent, in order to organize management. Lack of recognition of dementia in the elderly and delay in its diagnosis raise the question of screening to detect it at an earlier stage.

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.