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

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.

- 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.