INTERCEPTOR Project: From MCI to Dementia
Condition: Mild Cognitive Impairment; Alzheimer Disease
MeSH terms: Alzheimer Disease; Dementia; Cognitive Dysfunction
Study type: Observational

Summary: 
      In the next years a number of phase 2-3 trials which utilize experimental drugs possibly
      disease modifying for Alzheimer Dementia will reach their conclusion. This dense clinical
      trials activity has triggered a fundamental question both from Patients and Scientific
      Communities and Health Authorities/Insurances: on which basis will the new drugs -if
      effective-be distributed to patients or at-risk population? This question mainly deals with
      the "MCI prodromal to AD"condition since the MCI population actually includes about 50% of
      those who will progress to AD (the real "prodromic to AD" MCI form) while the remaining 50%
      will never convert to AD.

      The INTERCEPTOR project is focused on the prodromic AD condition (IWG2) or the MCI condition
      (NIA-AA) which form the neuropsychological point of view and is characterized by means of:
      cognitive questionnaires, screening test (MMSE), extended neuropsychological evaluation.

      The study is an observational, longitudinal cohort one, in which the baseline clinical and
      biomarkers characteristics of the enrolled MCI subjects at baseline will be compared for
      those classified as "AD converters" after 3.0 years of follow-up with respect to those
      "non-converters". MCI subjects who will convert to other forms of dementia will be examined
      separately. It will be considered the conversion to Alzheimer's disease within 3.0 years
      after diagnosis of MCI, together with the assessment of those who remain in a stable
      condition and those who have a reversion to normal cognitive profile. People with MCI who
      convert to other forms of dementia will be considered separately. The biomarker or a set of
      biomarkers that can predict the conversion to Alzheimer's disease with higher accuracy will
      be evaluated.
    

Detailed description: 
      In the next 8 years a number of phase 2-3 trials will end up which utilize experimental drugs
      possibly disease modifying for Alzheimer Dementia. They target different disease stages:
      mild-moderate AD, 'early' AD, MCI prodromic to AD (MCI + for biomarkers heralding progression
      to AD), pre-symptomatic AD in pathogenetic gene mutation carriers of familiar AD forms. This
      dense clinical trials activity has triggered a fundamental question both from Patients and
      Scientific Communities and Health Authorities/Insurances: on which basis will the new drugs
      -if effective-be distributed to patients or at-risk population? This question mainly deals
      with the "MCI prodromal to AD"condition since the MCI population actually includes about 50%
      of those who will progress to AD (the real "prodromic to AD" MCI form) while the remaining
      50% will never convert to AD. Since the new drugs -if effective- will carry both elevated
      unit costs and not marginal side-effects, they should be administered selectively to those
      MCI with a severely high risk of conversion (i.e. 90% or more) and particularly to those with
      a highrisk of rapid conversion (1-2 years from diagnosis of the MCI condition).

      The INTERCEPTOR project is focused on the prodromic AD condition (IWG2) or the MCI condition
      (NIA-AA) which form the neuropsychological point of view and is characterized by means of:
      cognitive questionnaire, screening test (MMSE), extended neuropsychological evaluation (incl.
      2 episodic memory tests, language test, visuo-spatial abilities evaluation, behavioural
      scales, functional scales (Annex), full neurological examination. CDR must be 0.5. Atypical
      types of clinical presentations must be particularly considered (i.e. non amnesic debut) for
      a differential diagnosis where the role of biomarkers is pivotal.

      In Italy, according to a recent study, an MCI prevalence of 5.9% has been evaluated in over
      60 yrs population, with an increase of 4.5% between 60 & 69 yrs, of 5.8% between 70 & 79 yrs,
      and up to 7.1% in the 80 - 89 yrs range. On this epidemiological basis about 735.000 MCI
      cases are estimated for 2016in the resident Italian population. Multicentric non therapeutic
      cohort study in subjects fulfilling the MCI "core" criteria as defined by the National
      Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for
      Alzheimer's disease. The study design reflect a longitudinal cohort study in which the
      baseline clinical and biomarkers characteristics of the enrolled MCI subjects at baseline
      will be compared for those classified as "AD converters" after 3.0 years of follow-up with
      respect to those "non-converters". MCI subjects who will convert to other forms of dementia
      will be examined separately.

      All the medications at baseline are allowed without modifications for the whole protocol
      except for urgencies.

      Neuropsychological follow-up tests will be carried out at 6 months intervals (total 7 from
      T0= baseline to T6= 42 months).

      Within 60 days from T0 biomarkers must be carried out/collected including:

      MMSE & DRF - FCSRT) DNA extraction and ApoE typing Lumbar Puncture for Beta/Tau metabolites
      EEG for brain connectivity with graph theory MRI + hippocampal volumetry (18F)FDG-PET
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        MCI subjects
      
Biospecimen description: 
      ApoE test
    
Keywords: Mild Cognitive Impairment; Alzheimer Disease