Clinical trial NCT03153371: Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks
Official title: Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Keywords: Alzheimer's disease
Young-onset
variant
visuospatial
language
apraxia
control
dementia
memory
MRI
neurology
neuropsychology
brain
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: University of Southern California
First posted: 2017-05-15
Enrollment: 180
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility 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.

Primary outcomes:
measure: Alzheimer's disease Subtype
timeFrame: Performed at baseline
Secondary outcomes:
measure: Change in overall Neurological profile
timeFrame: Performed at baseline and 1-year follow-up visit
measure: Brain atrophy in MRI - Magnetic Resonance Imaging of the brain
timeFrame: Performed at baseline visit
measure: Change in overall Neuropsychological profile
timeFrame: Performed at baseline and 1-year follow-up visit
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Department of Neurology
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Mario F Mendez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: