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

University of California, Los Angeles (UCLA)

Status: Completed

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

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT03153371

1RF1AG050967-01A1 (U.S. NIH Grant/Contract)

1RF1AG050967

UCLA IRB#16-000496 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 180 patients

Sex: All

Ages: 50 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

• 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.

Trial design

180 participants in 3 patient groups

Early-onset Alzheimer's disease

Description:

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

Description:

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

Controls

Description:

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