Browsing by Author "Letra, L"
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- Association between Adipokines and Biomarkers of Alzheimer's Disease: A Cross-Sectional StudyPublication . Letra, L; Matafome, P; Rodrigues, T; Duro, D; Lemos, R; Baldeiras, I; Patrício, M; Castelo-Branco, M; Caetano, G; Seiça, R; Santana, IBACKGROUND: Adipose tissue dysfunction has been implicated in the pathophysiology of Alzheimer's disease. However, the involvement of adipokines, particularly adiponectin, remains unclear. OBJECTIVE: To compare serum and cerebrospinal fluid (CSF) levels of adiponectin, leptin and leptin-to-adiponectin ratio in patients within the spectrum of Alzheimer's disease and evaluate their relationship with classical biomarkers and their value as markers of progression. METHODS: Amnestic mild cognitive impairment (MCI, n = 71) and Alzheimer's dementia (AD, n = 53) subjects were consecutively recruited for serum and CSF adiponectin and leptin determination using an analytically validated commercial enzyme-linked immunosorbent assay (ELISA). Correlations were explored using adjusted Spearman's correlation coefficients. A logistic regression model and ROC analysis were performed to evaluate the staging predictive value of adipokines. RESULTS: Serum adiponectin was 33% higher in AD when compared to MCI patients. Adiponectin CSF levels, similar in both groups, were positively correlated with Aβ42 and cognitive function, though only in women. The area under the ROC curve was 0.673 (95% CI:0.57-0.78) for serum adiponectin as predictor of dementia stage and the cut-off 10.85μg/ml maximized the sum of specificity (87%) and sensitivity (44%). CONCLUSION: Although longitudinal studies are required, we hypothesize that higher serum adiponectin in AD patients constitutes a strategy to compensate possible central signaling defects. In addition, adiponectin might be specifically assigned to neuroprotective functions in women and eventually involved in the female-biased incidence of Alzheimer's disease.
- Frontotemporal dementia: neuroanatomical correlates of an atypical presentationPublication . Felix-Morais, R; Letra, L; Duro, D; Santana, IFrontotemporal dementia (FTD) is a heterogeneous group of disorders characterised by frontal and temporal lobes atrophy. Three different clinical subtypes are recognised: behavioural variant, progressive non-fluent aphasia and semantic dementia. Neuroanatomical associations in a diffuse neurodegenerative disease such as FTD should be interpreted carefully; however, each FTD subtype has provided a clinical model that has contributed immensely to our understanding of clinical/neuroanatomical relationships. This case report and recent studies suggest that neuroanatomical findings concerning face-processing mechanisms in FTD can identify the brain regions that are critical for face processing. As seen in this case, right fusiform gyrus atrophy seems to be implied in the aetiology of prosopagnosia.
- Obesity as a risk factor for Alzheimer's disease: the role of adipocytokinesPublication . Letra, L; Santana, I; Seiça, RAlzheimer's disease is the leading cause of dementia and the most prevalent neurodegenerative disease. It is an aging-related multi-factorial disorder and growing evidence support the contribution of metabolic factors to what was formerly thought to be a centrally mediated process. Obesity has already been recognized as an important player in the pathogenesis of this type of dementia, independently of insulin resistance or other vascular risk factors. Although the exact underlying mechanisms are still unknown, adipocyte dysfunction and concomitant alteration in adipocyte-derived protein secretion seem to be involved, since these adipocytokines can cross the blood-brain barrier and influence cognitive-related structures. Very few studies have assessed the role of adipocytokines dysfunction on cognitive impaired patients and yielded contradictory results. Interestingly, extensive research on the central effects of leptin in Alzheimer's disease-transgenic mice has demonstrated its capacity to enhance synaptic plasticity and strength, as well as to prevent beta-amyloid deposition and tau phosphorylation. In addition, adiponectin, the most abundant adipocytokine whose levels are inversely correlated to adiposity, has shown to be neuroprotective to hippocampal cells. Many other adipose-derived cytokines have mainly pro-inflammatory properties, being able to trigger and/or enhance central inflammatory cascades and also to influence the secretion of other adipocytokines involved in cognition. This paper pretends to review the existing evidence on the contribution of adipocytokines dysfunction to the increased risk of dementia associated with mid-life obesity, unraveling its insulin-independent effects on cognition.