Evaluation of a Computerized Complex Instrumental Activities of Daily Living Marker (NMI)
Condition: Alzheimer Disease; Mild Cognitive Impairment; Memory Disorders; Cognitive Impairment; Dementia; Presymptomatic Disease
MeSH terms: Alzheimer Disease; Memory Disorders; Asymptomatic Diseases; Cognitive Dysfunction
Study type: Interventional

Summary: 
      The proposed study is designed to evaluate the performance of the ALTOIDA™ System as a tool
      to assist physicians in diagnosing Alzheimer's Disease (AD) in real-world clinical settings.
      The design of this study is guided by two overriding factors: 1) to optimize the performance
      of the ALTOIDA™ Neuro Motor Index (NMI) prognosis classifiers, the subjects making up the
      training sets must be well characterized as to their clinical diagnosis, and 2) all ALTOIDA™
      tests must be performed and reproduced in real-world clinical settings.

      Although there is already a large body of peer-reviewed scientific literature demonstrating
      that certain digital biomarker patterns are associated with certain neurologic conditions,
      the utilization of such tools for the evaluation of neurologic disorders is still considered
      an emerging science and therefore in the investigational stage. Although this protocol will
      report on brain patterns of certain neurologic conditions such as cognitive impairment and
      Alzheimer's disease, based on patterns published in peer-reviewed journals, such findings are
      not considered stand alone or diagnostic per se and should always be considered by the
      primary physician in conjunction with the patient's clinical condition. These data should
      only be used as additional information to add to the primary physician's diagnostic
      impression.
    

Detailed description: 
      The goal of the study is to determine relationships among the clinical, cognitive, imaging,
      genetic, and biochemical biomarker characteristics of the stage of the AD spectrum that
      precedes MCI, the mildest symptomatic phase of AD, referred to here as MCI. The ADNI-GO model
      posits that AD begins with amyloid β (Aβ) deposition in the cortex, which leads to synaptic
      dysfunction, neurodegeneration, and cognitive/ functional decline.

      It may be possible to determine the future development of ALZ in a preclinical state in a
      cognitively normal but high risk individual at least 18-24 months before any symptoms develop
      of cognitive impairment. In addition a newly proposed research framework proposes to use
      biomarkers for amyloid, tau, and neurodegeneration (ATN) to classify MCI patients.

      Some of the leading-edge technologies under study are brain-imaging techniques, such as
      positron emission tomography (PET), including FDG-PET (which measures glucose metabolism in
      the brain); PET using a radioactive compound (F-AV-45) that measures brain beta-amyloid; and
      structural MRI. Brain scans are showing scientists how the brain's structure and function
      change as AD starts and progresses. Biomarkers in cerebrospinal fluid are revealing other
      changes that could identify which patients with MCI will develop Alzheimer's. Scientists are
      looking at levels of beta-amyloid and tau in cerebrospinal fluid. (Abnormal amounts of the
      amyloid and tau proteins in the brain are hallmarks of Alzheimer's disease.)

      The aim of the study is to evaluate the performance of the ALTOIDA™ System as as a tool to
      assist physicians in diagnosing Alzheimer's Disease (AD) in real-world clinical settings.

      The study will be :

      A. Multi-Center Study:

      primary goal of this study will be to evaluate the ALTOIDA™ Platform across multiple study
      locations. This will demonstrate an ability to perform tests, collect data, and generate
      classifications irrespective of variations in testing locations and personnel.

      12 international study sites will be selected with the US based sites being a recognized NIH
      Center of Excellence for Alzheimer's disease or other nationally recognized Alzheimer's
      disease research center. Each site will evaluate up to 60 community dwellers evenly divided
      between MCI patients and age-matched controls (while the prevalence of AD is approximately
      12% in the general population, the ratio of AD to normal among those who visit a clinic for
      memory or cognitive related issues is between 50-60%).

      Each site will follow the same testing protocols. Participants will be asked if they would
      like to participate in a protocol that monitors their prospective risk for developing ALZ
      short term, and whether certain of their prescribed medications may have a protective effect.
      Those who are accepting to be participants are then enrolled in the study.

      Enrollees will be tested for risk factors for having pre-clinical ALZ. Individuals identified
      as being at risk at baseline are followed at 6 month intervals for a 48 month period using
      psychometric testing and functional neuroimaging. Their maintenance of cognitive stability or
      cognitive decline is monitored while under the care of their PMD and while taking medications
      of interest.

      All test data will be uploaded to the online ALTOIDA™ database server.

      B. The overall impact of this study will be increased knowledge concerning the sequence and
      timing of events leading to MCI and from MCI to AD, development of better clinical and Neuro
      Motor Index prognosis methods for early detection and for monitoring the progression of these
      conditions, and facilitation of clinical trials of treatments to slow disease progression,
      ultimately contributing to the prevention of AD.
    

Intervention name(s): Altoida: neuropsychological, MRI, EEG and CSF biomarkers
Intervention type(s): Other
Intervention description(s): Data collection at baseline: clinical (neurological, activity of the daily life, instrumental activity of the daily life, depression scale), standard neuropsychological exam, ALTOIDA and neurophysiology (EEG/ERPs) in both Prodromal and Preclinical AD subjects. In both Prodromal and Preclinical AD subjects, APOE genotyping. The local clinical Unit should document the positivity at the baseline session of at least one of the biomarkers of AD mentioned above.
Data collection at 6, 12, 24 and 36 months of follow up: clinical (neurological, activity of the daily life, instrumental activity of the daily life, depression scale), standard neuropsychological exam, ALTOIDA and neurophysiology (EEG/ERPs) in both Prodromal and Preclinical AD subjects.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Adults at high risk of developing ALZ within 18-40 months (MCI) or cognitively normal for their age sex matching group. Risk factors include parents with a history of ALZ, and/or positive APOE4 alleles.
Masking: Double (Participant, Investigator)
Primary purpose: Diagnostic
Keywords: biomarkers; CSF; EEG; MRI; Digital biomarkers