Late-Life Depression versus Amnestic Mild Cognitive Impairment: Alzheimer's Disease Incidence in 4 Years of Follow-Up.

BACKGROUND/AIM: The aim of the study was to evaluate the prognostic power of late-life depression (LLD) compared with amnestic mild cognitive impairment (aMCI) for the onset of Alzheimer's disease (AD) within 4 years of follow-up. METHODS: We estimated the incidence of AD in 60 patients presenting with aMCI, 115 patients suffering of LLD treated with antidepressants with good compliance, and 66 healthy control (HC) patients, followed for 4 years. RESULTS: The risk to develop AD, within 4 years, was 68.33% for aMCI and 49.57% for LLD. In AD patients 5.60% deteriorated without depression, and 72.20% deteriorated with depression after 4 years of follow-up (p < 0.0001). No HC patients deteriorated to AD or any other dementia type. CONCLUSION: In our results, aMCI was the first predictive condition that increased the risk to develop AD. Depression is a potentially preventable medical condition across the lifespan and may be a modifiable risk factor.

Association between R2CHA2DS2-VASc score and three-vessel coronary artery disease in a large population at high cardiovascular risk.

Coronary artery disease (CAD), particularly three-vessel coronary disease (3VD), is the main cause of death in industrialized countries. Chronic kidney disease is an independent risk factor for CAD. The CHA2DS2-VASc score shows a good ability to predict CV events in high-risk population independently from atrial fibrillation. The aim of the present study was to evaluate the association between the R2CHA2DS2-VASc score and 3VD in a population of patients at high cardiovascular risk. Monocentric prospective study evaluated 1017 patients undergoing coronary angiography. The R2CHA2DS2-VASc score was obtained by adding 2 points to the CHA2DS2-VASc score in case of eGFR < 60 ml/min/1.73m2. Coronary lesions causing ≥ 50% reduction of a major epicardial vessel diameter were considered significant. Patients were grouped based on R2CHA2DS2-VASc tertiles and according to the severity of CAD: 3VD vs No-3VD. The 3VD group showed significantly higher R2CHA2DS2-VASc score than the No-3VD group (4.20 ± 2.18 vs 3.36 ± 2.06, p < 0.001). The risk of 3VD increased by 21% for every 1-point increase in the score (OR 1.21; 95% CI 1.13-1.28, p < 0.001). The prevalence of 3VD was higher among patients belonging to higher tertiles of R2CHA2DS2-VASc (17.2% vs 26.7% vs 33.6% for first, second, and third tertile respectively, p < 0.001) with a risk more than doubled for the third tertile compared to the first one (OR 2.45; 95% CI 1.71-3.49, p < 0.001). The R2CHA2DS2-VASc score is independently associated with 3VD in patients at high cardiovascular risk. The score could be considered a useful tool for clinicians to identify patients who are at high risk of 3VD.

Renal Resistive Index of the Main Renal Arteries and Transmitral Flow in Hypertensive Patients.

In hypertensive patients, diastolic dysfunction is related to increased resistive index (RI) of parenchymal renal arteries. To determine the existence of a link between RI of the main renal arteries (RRI) and diastolic dysfunction, a group of 127 hypertensive patients, with glomerular filtration rates >50 mL/min (mean estimated glomerular filtration rate: 88.6 ± 15.2 mL/min) and no comorbidities, was studied. RRI and transmitral flow were evaluated using the deceleration time (DT) and E/A ratio. A statistically significant correlation between RRI and DT (>240 ms) was noted (p < 0.001). The RRI cutoff that best discriminated patients with DT >240 ms was 0.675. For each unitary increment of 10 mm in DT, the log-transformed RRI significantly increased by a mean of 0.006 point (p < 0.001). This study revealed the importance of the link between RRI and transmitral DT in addition to the renowned significance of the increase in RI as a cardiovascular risk factor in hypertensive patients without comorbidities.

Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer's disease.

BACKGROUND: Serotoninergic pathways underlying delusion symptoms in Alzheimer's disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription. METHODS: We investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer's Association criteria. All participants underwent a comprehensive evaluation with a standardized comprehensive geriatric assessment and Neuropsychiatric Inventory. RESULTS: Delusion symptoms were observed in 171 patients (66.54%). In respect to AD patients without delusions, AD patients with delusions showed a low prevalence of S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes) [p < 0.001; odds ratio (OR) = 0.240, 95% confidence interval (CI) = 0.121-0.471]. Logistic regression analysis adjusted for the apolipoprotein E polymorphism showed that in AD patients with delusions the presence of an 5-HTTLPR-S allele may reduce disease duration (p = 0.005; OR = 0.680, 95% CI = 0.522-0.886) and increase aberrant motor activity (p = 0.013; OR = 2.257, 95% CI = 1.195-4.260). The present findings suggested that 5-HTTLPR might be associated with delusions in AD. S-plus carriers might be associated with protective effect against delusions in AD. CONCLUSIONS: More studies on wider samples of high selected demented patients are needed to confirm our results. However, the present findings suggested that a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of neuropsychiatric clusters in AD with important implications regarding mechanisms underlying delusions and their possible treatment across the AD and dementia spectrum.

Neurocognitive Disorders and Dehydration in Older Patients: Clinical Experience Supports the Hydromolecular Hypothesis of Dementia.

Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer’s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS). For each patient, the equation for serum osmolality developed by Khajuria and Krahn was applied. Five hundred and seventy-one patients had cognitive decline and/or depression mood (CD-DM) and 520 did not have CD-DM (control group). Patients with CD-DM were less likely to be male (p < 0.001), and were more likely to be older (p < 0.001), have a significant clear cognitive impairment (MMSE: p < 0.001), show the presence of a depressive mood (HDRS-21: p < 0.001) and have major impairments in ADL (p < 0.001), IADL (p < 0.001), MNA (p < 0.001), and ESS (p < 0.001), compared to the control group. CD-DM patients had a higher electrolyte concentration (Na⁺: p < 0.001; K⁺: p < 0.001; Cl−: p < 0.001), risk of dehydration (osmolality p < 0.001), and kidney damage (eGFR: p = 0.021), than the control group. Alzheimer’s disease (AD) patients showed a major risk for current dehydration (p ≤ 0.001), and dehydration was associated with the risk of developing a type of dementia, like AD or vascular dementia (VaD) (OR = 2.016, p < 0.001). In the multivariate analysis, the presence of dehydration state was associated with ADL (p < 0.001) and IADL (p < 0.001), but independently associated with age (r² = 0.0046, p = 0.77), ESS (r² = 0.0052, p = 0.54) and MNA (r² = 0.0004, p = 0.48). Moreover, younger patients with dementia were significantly more dehydrated than patients without dementia (65⁻75 years, p = 0.001; 76⁻85 years, p = 0.001; ≥86 years, p = 0.293). The hydromolecular hypothesis intends to explain the relationship between dehydration and cognitive impairment in older patients as the result of protein misfolding and aggregation, in the presence of a low interstitial fluid volume, which is a defect of the microcirculation. Defective proteins were shown to impair the amount of information in brain biomolecular mechanisms, with consequent neuronal and synaptic damage.

[Between old and new targets: blood pressure control in hypertensive outpatients].

OBJECTIVE: In developed countries, blood pressure (BP) control has increased over the past few decades and is now approaching 70% of patients. Herewith we report the results of a cross-sectional study carried out on hypertensive outpatients. DESIGN AND METHODS: In a cohort of 1,412 consecutive hypertensive outpatients (790 females, 622 males; mean age: 60.3±12.2 years) evaluated from January 2015 to December 2016, the following parameters were assessed: age, gender, body mass index (BMI), waist circumference (WC), smoking habits, BP in the sitting position, estimated glomerular filtration rate (eGFR), serum glucose, lipid profile, antihypertensive drugs prescribed. In agreement with the European guidelines, hypertension was defined as sitting BP ≥140/90 mmHg or use of antihypertensive drugs. Patients whose BP was <140/90 mmHg were considered as having achieved BP control. Furthermore, in compliance with the redefinition of hypertension suggested by the American College of Cardiology/American Heart Association (ACC/AHA), a second level of BP control (BP <130/80 mmHg) was evaluated. RESULTS: Overall, 75.7% of hypertensive patients achieved BP levels <140/90 mmHg, while 50.5% achieved BP levels <130/80 mmHg. In both contexts, compared with patients whose BP was not controlled, those achieving the BP targets were mainly younger and females with a lower prevalence of obesity, diabetes and chronic kidney disease. Furthermore, they also had a lower WC and a higher eGFR. CONCLUSIONS: Nearly 76% of patients achieved the BP target of <140/90 mmHg, a result which is higher than the 70% achieved in Europe, and 50.6% achieved that of <130/80 mmHg, a result which is slightly higher than the 47% recently reported in USA.

Executive Dysfunction Detected with the Frontal Assessment Battery in Alzheimer's Disease Versus Vascular Dementia.

Alzheimer's disease (AD) and vascular dementia (VaD) lead to progressive decline in executive function. We estimated the prevalence of executive dysfunction in AD and VaD patients, investigating cognitive, functional, and clinical correlates and also using a multidimensional approach based on a standardized comprehensive geriatric assessment (CGA). We included 215 patients (115 AD patients and 100 VaD patients) consecutively evaluated with a complete cognitive and affective assessment, a CGA, and the Frontal Assessment Battery (FAB) with six subtests investigating conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. The prevalence of dysexecutive syndrome screened with a FAB score <12 points was high in both AD (97 patients) and VaD (77 patients) (84.3% versus 77.0%, p = 0.171). AD patients were significantly younger, with higher grade of cognitive impairment and less severe comorbidity and polypharmacy than VaD patients. AD patients showed a significantly higher impairment in FAB total score and five FAB subtests (conceptualization, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy) than VaD patients. These findings were largely confirmed in a sub-analysis conducted subdividing the sample in mild and moderate-to-severe demented patients and suggesting that in moderate-to-severe AD there was higher impairment in FAB total score and four FAB subtests (conceptualization, sensitivity to interference, inhibitory control, and environmental autonomy). Executive dysfunction could be greater in AD patients with moderate-to-severe dementia compared to VaD patients, although our groups were also not matched for age, comorbidity or polypharmacy, which could also exert an effect.

Effects of oral amino acid supplementation on Multidimensional Prognostic Index in hospitalized older patients: a multicenter randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: It is not known whether amino acid supplementations may influence health status in hospitalized older acutely ill patients. AIM: The aim of this study was to determine whether nutritional supplementation with amino acids (Aminoglutam®) is associated with multidimensional improvement assessed with the Multidimensional Prognostic Index (MPI). METHODS: In this randomized, double-blind, placebo-controlled pilot clinical trial, 126 patients aged ≥65 years were enrolled from 6 Italian geriatric wards. A multidimensional assessment to calculate the MPI was performed at baseline and after 4 weeks of treatment with nutritional supplementation (96 kcal, 12 g amino acids, 0.18 g fat, 11.6 g carbohydrate, and vitamins B1, B6, and C) or placebo administered twice a day. Logistic regression modeling was applied to determine the effect of treatment on the improvement of MPI (vs no-change/worsening), adjusting for gender, age, and MPI at baseline. Treatment's interactions with age, gender, and MPI at baseline were tested adding the appropriate interaction parameter in the regression models. RESULTS: Of the 126 patients included, 117 patients (93%) completed the study. A significant improvement in the MPI score was detected in the overall population (mean difference post-pretreatment: -0.03, p=0.001), with no differences between active and placebo arms. Men in the amino acid supplementation group had a significantly higher rate of improvement in MPI (81%) compared to the placebo group (46%) (Fisher's exact test p=0.03). Adjusting for age, diagnosis, and MPI at baseline, amino acid treatment was shown to be associated with an improvement in MPI in men (OR=4.82, 95% confidence interval [CI]: 0.87-26.7) and not in women (OR=0.70, 95% CI: 0.27-1.81). The interaction effect between active treatment and gender was significant (p=0.04). CONCLUSION: A 4-week amino acid supplementation improved the MPI significantly in hospitalized older male patients but not in female patients. Further studies are needed to confirm the gender effect of amino acid supplementation on MPI in older patients.

Delusions in Patients with Alzheimer's Disease: A Multidimensional Approach.

In Alzheimer's disease (AD) patients with delusions, clinical outcomes and mortality result from a combination of psychological, biological, functional, and environmental factors. We determined the effect of delusions on mortality risk, clinical outcomes linked to comprehensive geriatric assessment (CGA), cognitive, depressive, and neuropsychiatric symptoms (NPS) in 380 consecutive AD patients with Mini-Mental State Examination, Clinical Dementia Rating scale, 15-item Geriatric Depression Scale, and Neuropsychiatric Inventory (NPI), assessing one-year mortality risk using the Multidimensional Prognostic Index (MPI). We included 121 AD patients with delusions (AD-D) and 259 AD patients without delusions (AD-noD). AD-D patients were significantly older, with higher age at onset and cognitive impairment, a more severe stage of dementia, and more depressive symptoms than AD-noD patients. Disease duration was slightly higher in AD-D patients than in those without delusions, although this difference was not statistically significant. At CGA, AD-D patients showed a higher grade of disability in basic and instrumental activities of daily living, and an increased risk of malnutrition and bedsores. The two groups of patients significantly differed in MPI score (AD-D: 0.65 versus AD-noD: 0.51, p <  0.0001) and MPI grade. AD-D patients showed also a significant higher score in NPI of the following NPS than AD-noD patients: hallucinations, agitation/aggression, depression mood, apathy, irritability/lability, aberrant motor activity, sleep disturbances, and eating disorders. Therefore, AD-D patients showed higher dementia severity, and higher impairment in cognitive and depressive symptoms, and several neuropsychiatric domains than AD-noD patients, and this appeared to be associated with higher multidimensional impairment and increased risk of mortality.