High Degree of Heterogeneity in Alzheimer's Disease Progression Patterns

Abstract

There have been several reports on the varying rates of progression among Alzheimer's Disease (AD) patients; however, there has been no quantitative study of the amount of heterogeneity in AD. Obtaining a reliable quantitative measure of AD progression rates and their variances among the patients for each stage of AD is essential for evaluating results of any clinical study. The Global Deterioration Scale (GDS) and Functional Assessment Staging procedure (FAST) characterize seven stages in the course of AD from normal aging to severe dementia. Each GDS/FAST stage has a published mean duration, but the variance is unknown. We use statistical analysis to reconstruct GDS/FAST stage durations in a cohort of 648 AD patients with an average follow-up time of 4.78 years. Calculations for GDS/FAST stages 4–6 reveal that the standard deviations for stage durations are comparable with their mean values, indicating the presence of large variations in the AD progression among patients. Such amount of heterogeneity in the course of progression of AD is consistent with the existence of several sub-groups of AD patients, which differ by their patterns of decline.

Reducing Endogenous α-Synuclein Mitigates the Degeneration of Selective Neuronal Populations in an Alzheimer's Disease Transgenic Mouse Model

“…Alzheimer's disease (AD) is an heterogeneous neurodegenerative disorder (Schellenberg, 1995;Komarova and Thalhauser, 2011;Lam et al, 2013) that affects Ͼ5 million in the United States alone (Alzheimer's Association, 2015) and is characterized by the progressive accumulation of amyloid ␤ (A␤) and microtubule associated protein tau (Tau), leading to the selective degeneration of neurons in the neocortex, limbic system, and nucleus basalis, among others (Morrison and Hof, 2002;Saxena and Caroni, 2011;Mattsson et al, 2016). In addition to A␤ and Tau, recent studies have shown that ␣-synuclein (␣-syn) (Hansen et al, 1990;McKeith, 2006;Lippa et al, 2007;Larson et al, 2012;Winslow et al, 2014;Walker et al, 2015) and TAR DNA-binding protein (TDP)-43 (Wilson et al, 2011;Colom-Cadena et al, 2013;Borchelt et al, 2014) might also contribute to the pathogenesis of AD.…”

Global Analysis of S-nitrosylation Sites in the Wild Type (APP) Transgenic Mouse Brain-Clues for Synaptic Pathology

“…The temporal progression of AD exhibits a highly variable pattern among patients and is not fully understood (31). Environmental, age-related, and genetic factors have been proposed to contribute to pathogenesis of the disease.…”

Longitudinal Progression of Cognitive Decline Correlates with Changes in the Spatial Pattern of Brain 18F-FDG PET

“…However, there can arise situations for which these assessments fail to adequately capture the disease progression (4). Test–retest reliability, learning effects, floor or ceiling effects, and variability in disease progression (5,6) can confound interpretation of these measures.…”