Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks (EOAD-Subtype)

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.

Study Overview

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

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.

• Study Type: Observational
• Enrollment (Actual): 180

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• 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.

Description

• 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 for control participants:

  1. Score 28/30 or higher on the Folstein Mini-Mental Status Exam.
  2. Age 40-85 years old
  3. Able to provide consent for participation and express willingness to participate in one-year follow-up visits.
  4. Have sufficient English fluency to complete neuropsychological testing in English.

• Exclusion criteria for control participants:

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Performed at baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in overall Neurological profile	Change in performance on neurological tasks between baseline visit and follow-up visit.	Performed at baseline and 1-year follow-up visit
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	Performed at baseline visit
Change in overall Neuropsychological profile	Change in neuropsychological performance over time.	Performed at baseline and 1-year follow-up visit

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Institute on Aging (NIA); University of Southern California
• Investigators: Principal Investigator: Mario F Mendez, MD, PhD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2016
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: April 27, 2017
• First Submitted That Met QC Criteria: May 11, 2017
• First Posted (Actual): May 15, 2017

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: MRI; memory; dementia; Alzheimer's disease; language; Young-onset; variant; visuospatial; apraxia; control; neurology; neuropsychology; brain
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Disease Attributes; Metabolic Diseases; Neurobehavioral Manifestations; Neurocognitive Disorders; Tauopathies; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Psychomotor Disorders; Communication Disorders; Language Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Late Onset Disorders; Corticobasal Degeneration; Alzheimer Disease; Dementia; Aphasia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Apraxias; Apraxia, Ideomotor
• Other Study ID Numbers: 1RF1AG050967 (U.S. NIH Grant/Contract); UCLA IRB#16-000496 (Other Identifier: UCLA Institutional Research Board); 1RF1AG050967-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No