Comparative Incidence of Conformational, Neurodegenerative Disorders.
BACKGROUND
The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs).


METHODS
We 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.


RESULTS
Based 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.


CONCLUSIONS
These 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.
Department of Applied Epidemiology, CNE, National Institute of Health Carlos III, Madrid, Spain; Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), National Institute of Health Carlos III, Madrid, Spain.
Jesús
J
de Pedro-Cuesta
Alzheimer's Disease Centre, Reina Sofia Foundation, Madrid, Spain.
Alberto
A
Rábano
Department of Applied Epidemiology, CNE, National Institute of Health Carlos III, Madrid, Spain; Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), National Institute of Health Carlos III, Madrid, Spain.
Pablo
P
Martínez-Martín
Department of Applied Epidemiology, CNE, National Institute of Health Carlos III, Madrid, Spain; Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), National Institute of Health Carlos III, Madrid, Spain.
María
M
Ruiz-Tovar
Department of Applied Epidemiology, CNE, National Institute of Health Carlos III, Madrid, Spain; Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), National Institute of Health Carlos III, Madrid, Spain.
Enrique
E
Alcalde-Cabero
Department of Applied Epidemiology, CNE, National Institute of Health Carlos III, Madrid, Spain; Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), National Institute of Health Carlos III, Madrid, Spain.
Javier
J
Almazán-Isla
Department of Applied Epidemiology, CNE, National Institute of Health Carlos III, Madrid, Spain; Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), National Institute of Health Carlos III, Madrid, Spain.
Fuencisla
F
Avellanal
Alzheimer's Disease Centre, Reina Sofia Foundation, Madrid, Spain; CIBERNED, National Institute of Health Carlos III, Majadahonda, Spain.
Miguel
M
Calero
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008268:Macular Degeneration / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000145:classification / Q000453:epidemiology*; D010641:Phenotype; D011328:Prions / Q000032:analysis; D012042:Registries; D016019:Survival Analysis; D055815:Young Adult
D011328:Prions