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

NCT ID: NCT03153371

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 180 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-04-04
• Study Completion Date: 2021-08-31

Brief 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.

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.

Conditions

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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).

No interventions assigned to this group

Alzheimer's disease

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

No interventions assigned to this group

Controls

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

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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

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

1. Complicating medical illnesses.

2. Significant primary visual impairments.

3. Major psychiatric illness not due to the dementia.

4. Confounding medications.

1. Complicating medical illnesses.

2. Significant primary visual impairments.

3. Major psychiatric illness not due to the dementia.

4. Confounding medications.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Mario F. Mendez

Professor of Neurology and Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mario F Mendez, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

UCLA Department of Neurology

Los Angeles, California, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

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Other Identifiers

UCLA IRB#16-000496

Identifier Type: OTHER

Identifier Source: secondary_id

1RF1AG050967-01A1

Identifier Type: NIH

Identifier Source: secondary_id

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1RF1AG050967

Identifier Type: NIH

Identifier Source: org_study_id

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