Clinical and biological predictors of Alzheimer's disease in patients with amnestic mild cognitive impairment

Abstract

Preditores clínicos e biológicos da evolução para doença de AbstractObjective: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. Method: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. Results: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during followup (odds ratio = 4.5, CI 95% [1.3-13.6], p = 0.010). At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ 42 , p = 0.020) and higher concentrations of total TAU (p = 0.030) and phosphorylated TAU (p = 0.010), as compared to non-converters. Discussion: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ 42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease. [1,3-13,6], p = 0,012 Descriptors

Platelet biomarkers in Alzheimer’s disease

“…The expression of total-and Ser-9 phosphorylated platelet GSK3B can be readily determined by Western-blot or ELISA methods, and enzymatic activity can be indirectly estimated by calculating the ratio between active and inactive forms. In a recent study by our group, platelet GSK3B activity was shown to be increased in pre-dementia stages of AD [39,40] , in accordance with the findings of Hye et al [41] of a marked increase in GSK3B activity in leukocytes of patients with AD and mild cognitive impairment (MCI).…”

“…In animal models, overactive GSK3B has been associated with memory impairment [34] . The phosphorylation of GSK3B at Serine 9 leads to its inactivation [35,36] , which may prevent Tau hyperphosphorylation and also have potential neuroprotective effects against Aβ toxicity [37,39] . GSK3B is also expressed in human platelets in higher amounts than in other blood cells.…”

A atividade da enzima Glicogênio Sintase Quinase 3 Beta (GSK-3B) em pacientes idosos com depressão maior: associação com parâmetros clínicos, psicopatológicos e cognitivos

“…Avaliação cognitiva através do CAMCOG e MEEM; a. A exclusão da presença de déficits cognitivos foi feita através da avaliação neuropsicológica e confirmada através de avaliações neuropsicológicas no acompanhamento destes idosos Forlenza et al, 2010).…”

“…Neste estudo, o aumento da atividade enzimática nos pacientes com CCL e DA se relacionou negativamente com a intensidade dos déficits cognitivos nestes pacientes. A magnitude do aumento da atividade da GSK-3B foi semelhante entre os pacientes deprimidos e os pacientes com CCL e DA observado no trabalho de Forlenza et al (2010).…”

“…Em ambas doenças observa-se uma redução do aporte neurotrófico e estimulação de cascatas pró-inflamatórias (Diniz et al, 2009;Diniz et al, 2010;Diniz et al, 2010;Diniz et al, 2010;Forlenza et al, 2009;Forlenza et al, 2010;Forlenza et al, 2011). Síndrome da resistência insulina é um fator de risco tanto para depressão maior quanto para DA (Baker et al, 2011;Schrijvers et al, 2010;Pan et al, 2008;Rasgon e Kenna, 2005 possa ser um marcador de estado dos episódios depressivos.…”