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):

• Meet criteria for AD.
• Meet clinical criteria for either typical amnestic AD or variant phenotypes of early-onset (EOAD, or "Type 2 AD").
• Mild-moderate dementia severity
• Sufficient English fluency to complete neuropsychological testing in English.
• Ability to provide consent for participation, or willingness to provide assent and a legally-authorized representative willing to provide surrogate consent.
• Availability of a caregiver informant for participation
• Exclusion criteria for patients with Alzheimer's disease (AD):

• Complicating medical illnesses.
• Significant primary visual impairments.
• Major psychiatric illness not due to the dementia.
• Confounding medications.
• Inclusion criteria for control participants:

• Score 28/30 or higher on the Folstein Mini-Mental Status Exam.
• Age 40-85 years old
• Able to provide consent for participation and express willingness to participate in one-year follow-up visits.
• Have sufficient English fluency to complete neuropsychological testing in English.
• Exclusion criteria for control participants:

• Complicating medical illnesses.
• Significant primary visual impairments.
• Major psychiatric illness not due to the dementia.
• Confounding medications.