%0 Journal Article %J J Alzheimers Dis %D 2018 %T Alzheimer's Disease Progression: Factors Influencing Cognitive Decline. %A Ferrari, Camilla %A Lombardi, Gemma %A Polito, Cristina %A Lucidi, Giulia %A Bagnoli, Silvia %A Piaceri, Irene %A Nacmias, Benedetta %A Berti, Valentina %A Rizzuto, Debora %A Fratiglioni, Laura %A Sorbi, Sandro %K Aged %K Aged, 80 and over %K Alleles %K Alzheimer Disease %K Apolipoprotein E4 %K Aspirin %K Cognitive Dysfunction %K Disease Progression %K Female %K Heterozygote %K Humans %K Italy %K Male %K Middle Aged %K Neuropsychological Tests %K Retrospective Studies %K Secondary Prevention %X

BACKGROUND: Alzheimer's disease (AD) patients present high variability in the rate of cognitive decline. Despite the wide knowledge on factors influencing dementia risk, little is known on what accounts for AD progression. Previous studies on this topic have mainly analyzed each factor separately without taking into account the interaction between genetic and non-genetic factors.

OBJECTIVE: The aim of the present study is to evaluate the role of demographic, clinical, therapeutic, and genetic factors and their interaction on cognitive decline among newly diagnosed AD patients.

METHODS: We retrospectively selected 160 AD patients diagnosed at the Neurology Unit of Careggi University Hospital of Florence. We evaluated the occurrence of rapid cognitive changes defined as the worsening of more than four points at the Mini-Mental State Examination after 2-year follow up period.

RESULTS: Among the 160 AD patients, 50% presented rapid disease progression. Extrapyramidal signs at disease onset were predictors of worse outcome (OR 2.2), especially among Apolipoprotein E (APOE) ɛ4 allele carriers, while the presence of family history for dementia decreased the risk of rapid progression by about 50%. Higher educated ɛ4-carriers showed a slower AD progression. We identified the chronic use of aspirin as potential secondary preventative strategy for the non ɛ4-carriers.

CONCLUSION: At dementia onset, some clinical and demographic data can be predictors of future progression. The outcomes of the present study support the already hypothesized interaction between genetic and non-genetic factors during disease course and suggest genetic-based approaches.

%B J Alzheimers Dis %V 61 %P 785-791 %8 2018 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/29226870?dopt=Abstract %R 10.3233/JAD-170665 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Association of the New Variant Tyr424Asp at TBK1 Gene with Amyotrophic Lateral Sclerosis and Cognitive Decline. %A Piaceri, Irene %A Bessi, Valentina %A Matà, Sabrina %A Polito, Cristina %A Tedde, Andrea %A Berti, Valentina %A Bagnoli, Silvia %A Braccia, Arianna %A Del Mastio, Monica %A Pignone, Alberto Moggi %A Pupi, Alberto %A Sorbi, Sandro %A Nacmias, Benedetta %K Aged %K Amyotrophic Lateral Sclerosis %K Aspartic Acid %K C9orf72 Protein %K Cognitive Dysfunction %K DNA Mutational Analysis %K Female %K Fluorodeoxyglucose F18 %K Genetic Association Studies %K Genetic Predisposition to Disease %K Humans %K Italy %K Male %K Mental Status and Dementia Tests %K Middle Aged %K Mutation %K Neuropsychological Tests %K Positron-Emission Tomography %K Protein-Serine-Threonine Kinases %K Tyrosine %X

A new risk gene associated with amyotrophic lateral sclerosis (ALS) has recently been identified: the Tank-binding kinase 1 (TBK1) gene. Up to now, 90 TBK1 variants have been described in ALS patients with or without frontotemporal dementia (FTD), thus making TBK1 the third or fourth most frequent genetic cause of ALS and FTD. A point mutation analysis in a cohort of 69 Italian ALS patients was performed in order to analyze the frequency of TBK1 mutations and the correlation with clinical phenotypes. The analysis identified the novel variant p.Tyr424Asp in a patient with a rapid progression of the disease. Our data supports the implication of TBK1 in ALS pathogenesis in Italy.

%B J Alzheimers Dis %V 61 %P 41-46 %8 2018 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/29103041?dopt=Abstract %R 10.3233/JAD-170694 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Low Florbetapir PET Uptake and Normal Aβ1-42 Cerebrospinal Fluid in an APP Ala713Thr Mutation Carrier. %A Lombardi, Gemma %A Berti, Valentina %A Tedde, Andrea %A Bagnoli, Silvia %A Piaceri, Irene %A Polito, Cristina %A Lucidi, Giulia %A Ferrari, Camilla %A Ginestroni, Andrea %A Moretti, Marco %A Pupi, Alberto %A Nacmias, Benedetta %A Sorbi, Sandro %K Alanine %K Alzheimer Disease %K Amyloid beta-Peptides %K Amyloid beta-Protein Precursor %K Aniline Compounds %K Brain %K Ethylene Glycols %K Humans %K Male %K Middle Aged %K Mutation %K Peptide Fragments %K Positron-Emission Tomography %K Threonine %X

According to the literature, the APP Ala713Thr mutation is associated with Alzheimer's disease and cerebral amyloid angiopathy. We describe a case of dementia clinically compatible with frontotemporal dementia in an APP Ala713Thr mutation carrier in which both [18F]Florbetapir PET uptake and Aβ1-42 cerebrospinal fluid levels were normal. Further evidences are required to establish if this association is only incidental.

%B J Alzheimers Dis %V 57 %P 697-703 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/28304299?dopt=Abstract %R 10.3233/JAD-161170