Mild cognitive impairment-to-Alzheimer's dementia progression risk: the contribution of the Interceptor project

Alzheimers Dement. 2026 Apr;22(4):e71204. doi: 10.1002/alz.71204.

Abstract

Background: Mild cognitive impairment (MCI) is an intermediate stage between normal and pathological brain aging, with 30% to 50% progressing to dementia within 3 to 5 years. Early identification of individuals at high risk of progression is crucial for public health strategies.

Methods: The INTERCEPTOR project included 398 MCI individuals. Baseline assessment included harmonized procedures for sociodemographic, clinical, neuropsychological, genetic (apolipoprotein E), cerebrospinal fluid (amyloid beta tau), electroencephalogram (brain connectivity), magnetic resonance imaging (hippocampal volumetry), and fluorodeoxyglucose positron emission tomography. The baseline and follow-up were completed by 351 individuals with MCI with neuropsychological tests every 6 months for 3 years.

Results: Dementia developed in 104 individuals (29.6%), including 85 (22.4%) who met core clinical criteria for probable and possible Alzheimer's disease dementia. A Cox model combining clinical and sociodemographic data achieved a concordance index of 72%, which increased to 82% when neuropsychology and biomarkers were added.

Discussion: The INTERCEPTOR nomogram represents a tool for predicting dementia progression risk, supporting public health strategies, including screening for risk assessment and risk/benefit ratio in innovative treatments.

Keywords: Alzheimer's disease; biomarkers; dementia; mild cognitive impairment; nomogram; prognostic model; public health strategies; risk stratification.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoproteins E / genetics
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / genetics
  • Cognitive Dysfunction* / pathology
  • Disease Progression*
  • Electroencephalography
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Risk Factors
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • tau Proteins
  • Biomarkers