Motivated by postmortem data, researchers evaluated a three-stage PET classification: low cortical; high cortical, low striatal; and high cortical, high striatal amyloid; hypothesizing this model could better reflect Alzheimer's dementia progression than a model based only on Amyloid  PET data expressed as cortical measures

Brain amyloid β (Aβ) deposition, one of the defining pathologies of Alzheimer's disease, is now detectable in vivo with high specificity using the PET, as confirmed at autopsy.

It is well established that elevated PET measures of brain Aβ increase risk for subsequent cognitive decline in both cognitively impaired and normal populations, and Aβ measures have been widely adopted as part of eligibility criteria for anti-Aβ therapeutic trials.

However, the subsequent decline of clinically normal (CN) individuals with elevated Aβ occurs slowly over several years and alternative PET measures that could predict decline over a shorter interval could potentially improve the efficiency of prevention trials.

This prospective study analyzed data from 1433 participants enrolled in either the Harvard Aging Brain study (HABS) or the Alzheimer's Disease Neuroimaging Initiative (ADNI). HABS is an ongoing, longitudinal, monocentric study conducted at Massachusetts General Hospital (USA).

ADNI is an ongoing, longitudinal, multicenter study conducted in 59 sites across the USA and Canada. Eligibility criteria and study designs of HABS and ADNI are similar: Normal participants, aged 55 to 94 years, are recruited from the community together with patients having the mild cognitive impairment (MCI) or Alzheimer's dementia (AD).

MRI and PET imaging data are acquired shortly after inclusion (baseline); cognitive follow-up data are acquired annually for virtually all participants, and imaging follow-up data are available in a subset of the participants.

They classified PET data from 1433 participants (646 normal, 574 mild cognitive impairment, and 213 AD), explored the successive involvement of cortex and striatum using 3-year follow-up PET data, and evaluated the associations between PET stages, hippocampal volumes, and cognition.

Results

Follow-up data indicated that PET detects amyloid first in cortex and then in the striatum. Their three-category staging including striatum better predicted hippocampal volumes and subsequent cognition than a three-category staging including only cortical amyloid.

PET can evaluate amyloid expansion from cortex to subcortex. Using striatal signal as a marker of advanced amyloidosis may increase predictive power in Alzheimer's dementia research.