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CompletedNCT03153371EOAD-SubtypeUpdated Apr 30, 2025

Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

An observational study in Alzheimer Disease, Early Onset, Alzheimer Disease and Alzheimer Disease, Late Onset, sponsored by University of California, Los Angeles. Completed at 1 site in United States. Open to participants aged 50 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-04-30.

Sponsored by University of California, Los Angeles · Observational

Study type
Observational
Model
Case-control
Time perspective
Prospective
Enrollment
180
Ages
50 Years to 85 Years
Sex
All
01

Study summary

This study attempts to identify two types of AD by using clinical and cognitive tasks and brain imaging. The subtypes of AD are separated into a "typical" group (memory loss) and a "variant" group (language, visuospatial, and other cognitive difficulties). Performance on the clinical tasks and brain imaging will be compared among the young-onset Alzheimer's disease group, a late-onset Alzheimer's disease group, and a control group.

Read the detailed description

Unlike the usual late-onset Alzheimer's disease (LOAD), early-onset AD (EOAD), with onset before age 65, includes a high percentage of phenotypic variants. These non-familial, variants (vEOAD) present, not with progressive memory loss, but with language, visuospatial, or other cognitive difficulties. AD is now understood as a disorder that manifests with disturbed cognition reflecting disturbed neural networks. A multivariate analysis of neuropsychological tests, the "gold standard" for objectively defining neurocognitive impairments, coupled with structural and functional neuroimaging analysis of connectomes, can identify the neurocognitive-neural network profiles of vEOAD patients, compared to those with typical AD. This knowledge can increase our understanding of the heterogeneity of AD and how it causes disease.

This study hopes to show that vEOAD constitutes a "Type 2 AD", by (1) defining the neuropsychological components of Type 2 AD, and (2) understanding the anatomy and atrophy of the brains of vEOAD patients. Together, these components can outline the neurocognitive-neural network profile of Type 2 AD.

In addition to information that can help in the diagnosis and management of EOAD, this study can stimulate novel research into the reasons for this neurobiological heterogeneity in AD and could potentially lead to interventions based on alternate neurocognitive-neural network profiles.

02

Conditions studied

  • Alzheimer Disease, Early Onset
  • Alzheimer Disease
  • Alzheimer Disease, Late Onset
  • Dementia, Alzheimer Type
  • Logopenic Progressive Aphasia
  • Primary Progressive Aphasia
  • Visuospatial/Perceptual Abilities
  • Posterior Cortical Atrophy
  • Executive Dysfunction
  • Corticobasal Degeneration
  • Ideomotor Apraxia

Keywords

  • Alzheimer's disease
  • Young-onset
  • variant
  • visuospatial
  • language
  • apraxia
  • control
  • dementia
  • memory
  • MRI
  • neurology
  • neuropsychology
  • brain
03

Who can participate

Ages eligible
50 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Patients with a diagnosis of early-onset Alzheimer's disease (EOAD; with a diagnosis before age 65), including early-onset neurodegenerative conditions such as primary progressive aphasia (PPA), other aphasias (logopenic, semantic, and non-fluent), posterior cortical atrophy (PCA), ideomotor limb apraxias, and executive dysfunction.

  • Inclusion criteria for patients with Alzheimer's disease (AD):

    1. Meet criteria for AD.
    2. Meet clinical criteria for either typical amnestic AD or variant phenotypes of early-onset (EOAD, or "Type 2 AD").
    3. Mild-moderate dementia severity
    4. Sufficient English fluency to complete neuropsychological testing in English.
    5. Ability to provide consent for participation, or willingness to provide assent and a legally-authorized representative willing to provide surrogate consent.
    6. Availability of a caregiver informant for participation
  • Exclusion criteria for patients with Alzheimer's disease (AD):

    1. Complicating medical illnesses.
    2. Significant primary visual impairments.
    3. Major psychiatric illness not due to the dementia.
    4. Confounding medications.

Inclusion criteria

  1. Score 28/30 or higher on the Folstein Mini-Mental Status Exam.

    1. Age 40-85 years old
    2. Able to provide consent for participation and express willingness to participate in one-year follow-up visits.
    3. Have sufficient English fluency to complete neuropsychological testing in English.

Exclusion criteria

  1. Complicating medical illnesses.

    1. Significant primary visual impairments.
    2. Major psychiatric illness not due to the dementia.
    3. Confounding medications.
04

Study design

Observational model
Case-control
Time perspective
Prospective
Enrollment
180 participants (actual)
Patient registry
No

Groups and cohorts

  • Early-onset Alzheimer's disease

    This group will include 90 patients who have been diagnosed with clinically probable early-onset Alzheimer's disease by the UCLA Neurology Clinic (60 variant phenotypes; 30 typical amnestic).

  • Alzheimer's disease

    This group will include 30 patients who have been diagnosed with clinically probable Alzheimer's disease (typical late-onset AD)

  • Controls

    Healthy age-matched individuals without clinically significant cognitive impairments will be enrolled into this study.

05

What researchers measure

Primary outcomes

  1. Alzheimer's disease Subtype

    Neuropsychological testing results for use in a two-stage multivariate diagnostic method that combines the (weighted) test results in order to best discriminate Type 2 AD and typical AD.

    Time frame: Performed at baseline

Secondary outcomes

  1. Change in overall Neurological profile

    Change in performance on neurological tasks between baseline visit and follow-up visit.

    Time frame: Performed at baseline and 1-year follow-up visit

  2. Brain atrophy in MRI - Magnetic Resonance Imaging of the brain

    Images from initial MRI scan taken at baseline visit will be analyzed for atrophy and white matter tract integrity

    Time frame: Performed at baseline visit

  3. Change in overall Neuropsychological profile

    Change in neuropsychological performance over time.

    Time frame: Performed at baseline and 1-year follow-up visit

06

Study locations

1 site
  • UCLA Department of Neurology
    Los Angeles, California 90095, United States
07

References and documents

Study documents

  • Informed consent form · Dec 19, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03153371
Lead sponsor
University of California, Los Angeles
Collaborators
National Institute on Aging (NIA), University of Southern California
Responsible party
Mario F. Mendez (Professor of Neurology and Psychiatry, University of California, Los Angeles) — Principal investigator
First posted
May 15, 2017
Start date
Apr 4, 2016
Primary completion
Aug 31, 2021
Completion
Aug 31, 2021
Last update
Apr 30, 2025

Study contacts

Mario F Mendez, MD, PhD
principal investigator · University of California, Los Angeles

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.

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