Cognitive impairment in remitted late-life depression is not associated with Alzheimer's disease-related CSF biomarkers.

BACKGROUND: Cognitive impairment is a common feature of late-life depression (LLD). Early studies using Alzheimer's disease (AD) biomarkers inferred a biological link between AD pathology and LLD, but recent findings have challenged this association. The aim of this investigation was to determine a panel of AD-related cerebrospinal fluid (CSF) biomarkers in a cross-section of elders with mild cognitive impairment (MCI) with and without LLD. METHODS: Subjects comprised 102 older adults: 27 with 'pure' amnestic MCI (aMCI), 53 with major depression and cognitive impairment - encompassing 22 late-onset (LOD) and 31 early-onset depression (EOD), and 22 euthymic elders without cognitive impairment (controls). Participants underwent lumbar puncture for determination of CSF concentrations of Aß1-42, T-tau, and P-tau. Cut-off scores for suspected AD were: Aß1-42 < 416p g/mL, P-tau > 36.1 pg/mL and Aß/P-tau ratio < 9.53 (O. V. Forlenza et al. 2015). Statistical analyses consisted of analyses of variance (ANOVA), analyses of covariance (ANCOVA), Bonferroni post-hoc tests, and Pearson's chi-squared tests. RESULTS: ANCOVA (age and schooling as covariates) displayed statistically significant results with respect to CSF biomarkers' profiles regardless of the socio-demographic divergencies previously identified by one-way ANOVA. Mean Aß1-42 values (pg/mL) were: aMCI, 360.3 (p < 0.001); LOD, 486.6 (p < 0.001); EOD, 494.2 (p < 0.001); controls, 528.3 (p < 0.001); p< 0.05. Mean Aß1-42/P-tau ratio: aMCI, 7.9 (p < 0.001); LOD 14.2 (p < 0.001); EOD, 15.3 (p < 0.001); controls, 17.1 (p < 0.001); p < 0.05. Post-hoc tests indicated that patients with aMCI showed significant differences in biomarker profile compatible with AD signature. LIMITATION: The main limitation is the relatively small sample. CONCLUSION: Our findings suggest that, distinctively from aMCI, cognitive impairment in LLD is not associated with AD's CSF pathological signature.

Safety Limits of Antidepressant Use Plus Combinations: Focus on Cardiovascular Function.

BACKGROUND: Antidepressants have been widely prescribed for depression, anxiety, sleep disorders, and in the management of behavioural symptoms of adult-old patients. Although generally safe, newer generation antidepressants are not devoid of the risk of inducing clinically relevant adverse events. OBJECTIVES: To investigate the association between newer generation antidepressants and the occurrence of cardiovascular adverse events and electrocardiogram (ECG) abnormalities. METHOD: Studies were included in the review according to the following criteria: a) clinical trials (placebo-controlled or not) or case reports; b) short- or long-term interventions with antidepressants; c) prescription of newer generation antidepressants as first-line treatment; d) samples of adult or adult-old patients. From a total of 301 articles addressing the association between antidepressants and cardiovascular adverse events as primary or secondary outcomes, we selected 30 controlled clinical trials and 10 case reports. RESULTS: In most clinical studies, the effects of antidepressants on cardiac function are usually computed as secondary outcome variables, however with limited information. Conversely, case reports tend to present more comprehensive sets of clinical and laboratorial parameters, but the generalization of such data is limited by the small number of observations. The occurrence of QTc prolongation (with increased risk of torsade de pointes) has been reported. Aging, higher dosages of antidepressants, drug interaction, and pre-existing cardiovascular comorbidities were found as risk factors for the aforementioned cardiovascular and ECG abnormalities. CONCLUSION: Prescribing antidepressants requires caution given their potential impact on cardiac function, and the clinician should carefully monitor cardiovascular and ECG parameters particularly in cases with underlying heart disease.

Neuropsychiatric symptoms in the prodromal stages of dementia.

PURPOSE OF REVIEW: To critically discuss the neuropsychiatric symptoms in the prodromal stages of dementia in order to improve the early clinical diagnosis of cognitive and functional deterioration. RECENT FINDINGS: Current criteria for cognitive syndrome, including Alzheimer's disease, comprise the neuropsychiatric symptoms in addition to cognitive and functional decline. Although there is growing evidence that neuropsychiatric symptoms may precede the prodromal stages of dementia, these manifestations have received less attention than traditional clinical hallmarks such as cognitive and functional deterioration. Depression, anxiety, apathy, irritability, agitation, sleep disorders, among other symptoms, have been hypothesized to represent a prodromal stage of dementia or, at least, they increase the risk for conversion from minor neurocognitive disorder to major neurocognitive disorder. Longitudinal investigations have provided increased evidence of progression to dementia in individuals with minor neurocognitive disorder when neuropsychiatric symptoms also were present. SUMMARY: Although neuropsychiatric symptoms are strongly associated with a higher risk of cognitive and functional deterioration, frequently the clinician does not acknowledge these conditions as increasing the risk of dementia. When the clinician accurately diagnoses neuropsychiatric symptoms in the prodromal stage of dementia, he could early establish appropriate treatment and, may be, delay the beginning of clinical and functional deterioration.