Elderly subjects diagnosed with mild cognitive impairment (MCI) are becoming the target of intervention trials. The criteria used for MCI are principally issued from prospective clinical studies, although longitudinal population-based studies having identified several cognitive predictors of dementia can be of great contribution in the definition of these criteria. This study was conducted to explore the external validity of MCI criteria issued from a longitudinal population-based study, and subsequently to identify the best predictors of the short-term conversion to Alzheimer's disease 2 years after the MCI diagnosis. Ninety elderly volunteers with memory complaint diagnosed with MCI on the basis of their functional and neuropsychological performances were followed up within 2 years. The potential predictors of the conversion to dementia collected at baseline included age, gender, educational level, size of temporal lobe, apolipoprotein E genotype and a series of neuropsychological measures (Mac Nair Scale, Mini-Mental State Examination, Benton Visual Retention Test, Isaacs Set Test, Digit Symbol Substitution Task, Letter Cancellation Task, digit span tasks and finger-tapping test). Within the 2 years, 29 subjects (32.2%) presented a conversion to dementia. The risk of conversion to dementia was associated with age and size of temporal lobe but not with gender, education, or apolipoprotein E4 genotype. Several neuropsychological measures were associated with the risk of conversion to dementia, but in a logistic regression performed with the significant variables found in the univariate analysis, only the Letter Cancellation Test was shown to be an independent predictor. In conclusion, the quite elevated conversion rates obtained show the usefulness, when defining MCI criteria, of considering not only memory impairment but also impairment in other cognitive areas, as well as mild impairment on higher-order activities of daily living. Among the variables considered, the Letter Cancellation Test proved to be a major predictor of short-term conversion to dementia.
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http://dx.doi.org/10.1159/000077815 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, United Kingdom.
The onset and development of Alzheimer's disease is linked to the accumulation of pathological aggregates formed from the normally monomeric amyloid-β peptide within the central nervous system. These Aβ aggregates are increasingly successfully targeted with clinical therapies at later stages of the disease, but the fundamental molecular steps in early stage disease that trigger the initial nucleation event leading to the conversion of monomeric Aβ peptide into pathological aggregates remain unknown. Here, we show that the Aβ peptide can form biomolecular condensates on lipid bilayers both in molecular assays and in living cells.
View Article and Find Full Text PDFAdv Protein Chem Struct Biol
January 2025
Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences Hospital (NIMHANS), Institute of National Importance, Bangalore, Karnataka, India. Electronic address:
Alzheimer's disease (AD) is a prevalent neurodegenerative disease associated with dementia and neuronal impairments in brain. AD is characterized histopathologically by two hallmark lesions: abnormally phosphorylated Tau inside neurons as intracellular NFTs and extracellular accumulation of amyloid β peptide (Aβ). Furthermore, it is unable to clarify the distinction between the brief association between the development and build-up of Aβ and the commencement of illness.
View Article and Find Full Text PDFAlzheimer Dis Assoc Disord
January 2025
Department of Cognition, Brain & Behavior Lab of Neuropsychology and Behavioral Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki.
Objective: Sleep disturbance is considered a risk factor for cognitive decline in elderly individuals. Our aim in the current study was to investigate whether baseline sleep parameters can predict the conversion from normal cognition to mild cognitive impairment or dementia at follow-up. The Hellenic Longitudinal Investigation of Aging and Diet is a longitudinal population-based study designed to estimate the prevalence and incidence of cognitive decline and dementia in the older Greek population.
View Article and Find Full Text PDFFront Cell Neurosci
January 2025
Department of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, United States.
Creutzfeldt-Jakob disease (CJD) is a rare, fatal, rapidly progressive neurodegenerative disease resulting from an accumulation of misfolded prion proteins (PrP). CJD affects 1-2 new individuals per million each year, and the sporadic type accounts for 90% of those cases. Though the median age at onset and disease duration vary depending on the subtype of sporadic CJD (sCJD), the disease typically affects middle-aged to elderly individuals with a median survival of 4-6 months.
View Article and Find Full Text PDFMov Disord
January 2025
Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Background: Central synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), involve alpha-synuclein accumulation and dopaminergic cell loss in the substantia nigra (SN) and locus coeruleus (LC). Pure autonomic failure (PAF), a peripheral synucleinopathy, often precedes central synucleinopathies.
Objectives: To assess early brain involvement in PAF using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and fluorodopa-positron emission tomography (FDOPA-PET), and to determine whether PAF patients with a high likelihood ratio (LR) for conversion to a central synucleinopathy exhibit reduced NM-MRI contrast in the LC and SN compared with controls and low-LR patients.
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