Efficacy and Safety of Citalopram Compared to Atypical Antipsychotics on Agitation in Nursing Home Residents With Alzheimer Dementia.

OBJECTIVE: To assess efficacy and safety of citalopram compared to quetiapine and olanzapine for the treatment of agitation in patients with Alzheimer disease (AD). DESIGN: Longitudinal, 6-month study. SETTING: Nursing home (NH). PARTICIPANTS: 75 NH residents with AD and agitation, randomized to citalopram (n = 25), quetiapine (n = 25), or olanzapine (n = 25). MEASUREMENTS: Changes in Neuropsychiatric Inventory (NPI) agitation subscale score and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) were used to assess treatment efficacy. Participants were surveilled for adverse health outcomes. RESULTS: Citalopram treatment (30±5.8 mg/d) resulted in similar 6-month efficacy compared to both quetiapine (94.0±40.4 mg/d) and olanzapine (5.2±1.6 mg/d), lower occurrence of falls than olanzapine [odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.68-0.97, P = .012], lower incidence of orthostatic hypotension than both quetiapine (OR = 0.80, 95% CI = 0.66-0.95, P = .032) and olanzapine (OR = 0.75, 95% CI = 0.69-0.91, P = .02), and less all-cause hospitalizations than both quetiapine (OR = 0.92, 95% CI = 0.88-0.95, P = .016) and olanzapine (OR = 0.78, 95% CI = 0.64-0.92, P = .004), after multiple adjustment for potentially confounding variables. No differences were observed for cognitive and functional decline, QTc prolongation, and infections. CONCLUSIONS: Citalopram resulted in similar efficacy and less adverse outcomes when compared to 2 atypical antipsychotics for treatment of agitation in NH residents with AD. Replication of these findings and assessment of long-term efficacy and safety of citalopram for treatment of neuropsychiatric symptoms in dementia are needed.

Dementia correlates with anticoagulation underuse in older patients with atrial fibrillation.

OBJECTIVES: Stroke prevention in older atrial fibrillation (AF) patients remains a challenge. This study aimed to investigate whether a dementia diagnosis is an independent correlate of lower prescription rate of oral anticoagulant treatment (OAT) in a sample of older AF patients. METHODS: Cross-sectional retrospective study. Consecutive older community-dwelling AF patients referred for a comprehensive geriatric assessment, were considered. Evaluation of physical, social and mental health, and administration of the Cumulative Illness Rating Scale (CIRS) and Barthel Index were performed. Dementia cases were ascertained by consensus of 2 experienced geriatricians. Dementia severity was assessed using the Clinical Dementia Rating scale (CDR). RESULTS: 316 AF patients (ages 74.7±7.0years, 55.7% women) with high stroke risk (77.5% had a CHA2DS2VASC score ≥3), low bleeding and falling risk, and no neuropsychiatric/behavioral symptoms, were included. 60.1% were prescribed with OAT. Among patients with dementia (n=86, 27.2%), 22.0% received inadequate antithrombotic prophylaxis (i.e. antiplatelet) and 38.5% no treatment. Proportion of those receiving inadequate or no prophylaxis increased at increasing CDR score. By multiple regression models, either dementia (yes vs no), OR=1.33, 95%CI=1.11-1.46, p<0.001, and dementia severity (CDR>1), OR=2.38, 95%CI=2.19-2.60, p<0.001, were associated with lack of OAT prescription independently of age, paroxysmal AF, and comorbidity burden. CONCLUSIONS: Dementia might be associated with underuse of OAT in older AF patients even in the absence of established contraindications. Future studies are needed to assess the real dimension of the problem and clinician's barriers to prescribing OAT in demented patients.

The Metabolic Syndrome Predicts Longitudinal Changes in Clock Drawing Test Performance in Older Nondemented Hypertensive Individuals.

OBJECTIVES: The present study evaluated the metabolic syndrome (MetS) as independent predictor of 1-year longitudinal changes in cognitive function. METHODS: 104 stroke- and dementia-free older hypertensive subjects were studied. MetS was defined by NCEP ATP-III criteria. Cognitive function was assessed by the Clock Drawing Test (CDT); 1-year changes in cognitive function were expressed as annual changes in CDT performance. Brain magnetic resonance imaging studies (1.5T) were performed. RESULTS: Participants with MetS exhibited greater cognitive decline than those without (-1.78 ± 1.47 versus -0.74 ± 1.44 CDT points, t = 3.348, df = 102, p < 0.001). MetS predicted cognitive decline (ß = -0.327, t = -3.059, df = 96, p = 0.003) independently of its components, age, baseline cognition, neuroimaging findings, blood pressure levels, and duration of hypertension. With the exception of systolic blood pressure, none of the individual components of MetS explained 1-year changes in CDT performance. CONCLUSIONS: MetS as an entity predicted accelerated 1-year decline in cognitive function, assessed by CDT, in a sample of older hypertensive subjects.

Executive dysfunction assessed by Clock-Drawing Test in older non-demented subjects with metabolic syndrome is not mediated by white matter lesions.

AIMS: Metabolic syndrome (MetS) has been associated with greater occurrence of white matter hyperintensities (WMH). It remains uncertain whether MetS as a construct is associated with poorer cognitive performances. This study explores whether MetS is associated with poorer performances in global and domain-specific cognitive tests in older non-demented subjects independently of its individual components, WMH severity and other variables. METHODS: MetS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III definition. Brain magnetic resonance studies (1.5T) were performed. Deep and periventricular WMH were graded using the Fazekas scale. Subjects underwent the Mini-Mental State Examination, the Babcock Short Story Recall test and the Clock-Drawing Test (CDT). RESULTS: Eighty community-dwellers aged 67-91 years were studied. Subjects with MetS (n = 35) had more severe WMH, and poorer performances on the CDT (P = 0.003) and the Babcock Short Story Recall test (P = 0.027). After multiple adjustment, MetS was inversely associated with CDT scores (B = -1.285; 95% confidence interval = -1.996--0.575; P = 0.001) but not with episodic memory. Results were not affected by WMH severity. Interestingly, none of the individual components of MetS predicted poorer cognitive performances. CONCLUSIONS: Impairment in executive functions assessed by CDT may represent an early and specific sign of cognitive decline in older individuals with MetS. Future longitudinal studies are needed to better establish the predictive role of MetS on dementia and to demonstrate the possibility of dementia prevention by targeting MetS.

Depressive symptoms in older people with metabolic syndrome: is there a relationship with inflammation?

OBJECTIVE: To investigate if there is a higher prevalence of depressive symptoms in older people with metabolic syndrome (MetS) compared with those without and whether dedpressive symptoms are independently associated to MetS and its single components and to the inflammatory markers. METHODS: Physical parameters, standard blood analytes, high sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were assessed. Fifteen-item Geriatric Depression Scale and mini mental state examination (MMSE) were administered. RESULTS: One hundred thirty-three subjects were enrolled. MetS patients (57) exhibited higher prevalence of depressive symptoms (p < 0.0001), worse cognitive function (p < 0.0001), and higher levels of ESR and hsCRP were higher (p < 0.0001). The univariate analysis showed a linear strong correlation of depressive symptoms (p < 0.0001) with the MMSE score (r = -0.422), body mass index (r = 0.414), MetS (r = 0.582), number of MetS components (r = 0.663), fasting blood glucose (r = 0.565), ESR (r = 0.565), hsCRP (r = 0.745), central obesity (r = 0.269; p = 0.002), and high-density lipoprotein cholesterol (r = -0.241; p = 0.005). However, the multivariate analysis showed that only age (B = -0.093; p = 0.032), MetS (B = 1.446; p = 0.025), fasting blood glucose (B = 0.039; p = 0.005), and hsCRP (B = 7.649; p < 0.0001) were independently associated with depressive symptoms. CONCLUSIONS: MetS and inflammation are independently associated with depressive symptoms in older people. Inflammation may explain cognitive decline too. Further investigations are needed to better understand the direction of these associations and to determine whether these can be reversible.

Screening cognition in the elderly with metabolic syndrome.

BACKGROUND: Metabolic syndrome reaches its highest prevalence in the elderly, and evidence suggests that metabolic syndrome could be an independent risk factor for cognitive impairment. The aims of this study were to detect whether patients with metabolic syndrome have lower cognition and to investigate whether there is a relationship with cognition and single metabolic syndrome components. METHODS: We assessed fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), triglycerides, high-sensitivity C-reactive protein (hsCRP), and anthropometric measurements. Metabolic syndrome was diagnosed according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. The population sample was divided into two groups according to the presence of metabolic syndrome. Cognitive function was investigated through the Mini-Mental State Examination (MMSE). RESULTS: We enrolled 159 elderly subjects (mean age, 69.8±4.8 years). Seventy had metabolic syndrome. Metabolic syndrome subjects had higher hsCRP values (P<0.0001) and lower MMSE scores (P<0.0001) than those without metabolic syndrome. MMSE scores were significantly correlated with body mass index (BMI), hsCRP, metabolic syndrome, the number of metabolic syndrome components, and each of them. However, at multivariate regression analysis, only fasting blood glucose [FBG; B=-0.046; 95% confidence interval (CI) -0.066 to -0.028; P<0.0001] and the number of metabolic syndrome components (B=-0.317; 95% CI -0.572 to -0.010; P=0.042) were found to be independent predictors of lower MMSE scores. CONCLUSION: We found that subjects with metabolic syndrome have lower MMSE scores than those without, even without symptomatic cognitive impairment, and that the number of metabolic abnormalities is independently associated to lower MMSE scores. We suggest that these patients should always undergo cognitive screening to prevent more severe outcomes.

[Vascular depression in the elderly. Does inflammation play a role?]. / La depressione vascolare nell'anziano. Quale ruolo per l'infiammazione?

Vascular depression in the elderly. Does inflammation play a role?Depression is the most common comorbidity in the elderly, and it is a major determinant of disability. The late-onset depression in highly associated to cardiovascular disease. Depressive symptoms may follow vascular brain damage, especially when mood regulating areas are affected. However depression is strongly associated to vascular disease even when there is no manifest brain damage. Recently great attention has been given to chronic inflammation, both related to depression and vascular disease. Both experimental and clinical evidence shows that a rise in the concentrations of proinflammatory cytokines and glucocorticoids in depressed patients is associated with defect in serotonergic function. Chronic inflammation may underlie many forms of depression associated with vascular disease and metabolic syndrome. The importance of the inflammation hypothesis of depression lies is that psychotropic drugs may have central anti-inflammatory action, and that new generation of central anti-inflammatory drugs may be useful in depression treatment.