Comparative Incidence of Conformational, Neurodegenerative Disorders.

Jesús De Pedro-Cuesta,Alberto Rábano,Enrique Alcalde-Cabero,Pablo Martínez-Martín,Fuencisla Avellanal,María Ruiz-Tovar,Javier Almazán-Isla,Miguel Calero,Luisa Gregori

doi:10.1371/journal.pone.0137342

Abstract

BackgroundThe purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs).MethodsWe identified 2563 reports on the incidence of eight conditions representing sporadic, acquired and genetic, protein-associated, i.e., conformational, NDD groups and age-related macular degeneration (AMD). We selected 245 papers for full-text examination and application of quality criteria. Additionally, data-collection was completed with detailed information from British, Swedish, and Spanish registries on Creutzfeldt-Jakob disease (CJD) forms, amyotrophic lateral sclerosis (ALS), and sporadic rapidly progressing neurodegenerative dementia (sRPNDd). For each condition, age-specific incidence curves, age-adjusted figures, and reported or calculated median survival were plotted and examined.FindingsBased on 51 valid reported and seven new incidence data sets, nine out of eleven conditions shared specific features. Age-adjusted incidence per million person-years increased from ≤1.5 for sRPNDd, different CJD forms and Huntington's disease (HD), to 1589 and 2589 for AMD and Alzheimer's disease (AD) respectively. Age-specific profiles varied from (a) symmetrical, inverted V-shaped curves for low incidences to (b) those increasing with age for late-life sporadic CNDDs and for sRPNDd, with (c) a suggested, intermediate, non-symmetrical inverted V-shape for fronto-temporal dementia and Parkinson's disease. Frequently, peak age-specific incidences from 20–24 to ≥90 years increased with age at onset and survival. Distinct patterns were seen: for HD, with a low incidence, levelling off at middle age, and long median survival, 20 years; and for sRPNDd which displayed the lowest incidence, increasing with age, and a short median disease duration.InterpretationThese results call for a unified population view of NDDs, with an age-at-onset-related pattern for acquired and sporadic CNDDs. The pattern linking age at onset to incidence magnitude and survival might be explained by differential pathophysiological mechanisms associated with specific misfolded protein deposits.

Highlights

Within the wide field of neurodegenerative disorders (NDDs), encompassing both highly frequent and rare ailments, the large aetiological NDD subgroup known as sporadic NDDs constitutes a major health problem in the industrial world
The sporadic NDDs (sNDDs) group embraces a variety of disorders, such as the sporadic forms of Alzheimer's disease (AD), essential tremor (ET), idiopathic Parkinson's disease (PD), Lewy body disease (LBD), fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), as well as a few rare, rapidly progressive disorders, among which sporadic Creutzfeldt-Jakob disease and non-prion sporadic rapid-progressive neurodegenerative dementia predominate [1,2]
In order to search for reported incidence measurements, we focused on: 1) sporadic Creutzfeldt-Jakob disease (sCJD), variant Creutzfeldt-Jakob disease (CJD), accidentally transmitted CJD, sporadic rapid-progressive neurodegenerative dementia (sRPNDd), ALS, FTD, PD, LBD and AD, as the most representative entities of the sporadic conformational neurodegenerative disorders (CNDDs) group, 2) two genetic CNDDs, namely, Huntington's disease (HD) and genetic transmissible spongiform encephalopathies; and, 3) late, age-related, macular degeneration (AMD), a highly prevalent disorder presenting with amyloid deposits in drusen [9,12,13]

Summary

Introduction

Within the wide field of neurodegenerative disorders (NDDs), encompassing both highly frequent and rare ailments, the large aetiological NDD subgroup known as sporadic NDDs (sNDDs) constitutes a major health problem in the industrial world. The term sporadic, equivalent to idiopathic, essentially denotes the absence of a known cause, as opposed to the genetic and acquired categories, which complete the aetiological spectrum and are well established only in prionrelated NDDs. The sNDD group embraces a variety of disorders, such as the sporadic forms of Alzheimer's disease (AD), essential tremor (ET), idiopathic Parkinson's disease (PD), Lewy body disease (LBD), fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), as well as a few rare, rapidly progressive disorders, among which sporadic Creutzfeldt-Jakob disease (sCJD) and non-prion sporadic rapid-progressive neurodegenerative dementia (sRPNDd) predominate [1,2]. The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs)

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