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

• ClinicalTrials.gov Identifier: NCT03153371
• Recruitment Status: Unknown
• First Posted: May 15, 2017
• Last Update Posted: April 28, 2020
• Sponsor: University of California, Los Angeles
• Collaborators: National Institute on Aging (NIA); University of Southern California
• Information provided by (Responsible Party): Mario F. Mendez, University of California, Los Angeles

Study Description

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.

Condition or disease
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

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 Design

• Study Type: Observational
• Estimated Enrollment: 180 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks
• Actual Study Start Date: April 4, 2016
• Estimated Primary Completion Date: March 31, 2021
• Estimated Study Completion Date: March 31, 2022

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. Alzheimer's disease Subtype [ Time Frame: Performed at baseline ]
   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.

Secondary Outcome Measures :

1. Change in overall Neurological profile [ Time Frame: Performed at baseline and 1-year follow-up visit ]
   Change in performance on neurological tasks between baseline visit and follow-up visit.
2. Brain atrophy in MRI - Magnetic Resonance Imaging of the brain [ Time Frame: Performed at baseline visit ]
   Images from initial MRI scan taken at baseline visit will be analyzed for atrophy and white matter tract integrity
3. Change in overall Neuropsychological profile [ Time Frame: Performed at baseline and 1-year follow-up visit ]
   Change in neuropsychological performance over time.

Eligibility Criteria

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

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.

Contacts and Locations

Contacts

Contact: Youssef I Khattab, BA; (310)-478-3711 ext 48176; YKhattab@mednet.ucla.edu

Contact: Elivra E Jimenez, PhD; (310)-478-3711 ext 40584 or 43389; eljimenez@mednet.ucla.edu

Locations

United States, California

UCLA Department of Neurology; Recruiting

Los Angeles, California, United States, 90095

Contact: Youssef I Khattab, BA 310-478-3711 ext 48176 YKhattab@mednet.ucla.edu

Contact: Elvira E Jimenez, PhD (310)-478-3711 ext 40584 or 43389 eljimenez@mednet.ucla.edu

Principal Investigator: Mario F Mendez, MD, PhD

Sponsors and Collaborators

University of California, Los Angeles

National Institute on Aging (NIA)

University of Southern California

Investigators

• Principal Investigator: Mario F Mendez, MD, PhD; University of California, Los Angeles

  Study Documents (Full-Text)

Documents provided by Mario F. Mendez, University of California, Los Angeles:

Informed Consent Form  [PDF] December 19, 2019

More Information

• Responsible Party: Mario F. Mendez, Professor of Neurology and Psychiatry, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT03153371
• 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 )
• First Posted: May 15, 2017
• Last Update Posted: April 28, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mario F. Mendez, University of California, Los Angeles:

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

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Aphasia; Apraxias; Aphasia, Primary Progressive; Pick Disease of the Brain; Frontotemporal Dementia; Apraxia, Ideomotor; Late Onset Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Psychomotor Disorders; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Disease Attributes; Pathologic Processes