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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Jennifer L Whitwell1

  • 1Mayo Clinic, Rochester, MN, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Neuroimaging biomarkers show promise for tracking Alzheimer's disease (AD) progression in atypical forms. Understanding atrophy patterns and tau deposition is crucial for optimizing clinical trials in diverse AD patient groups.

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Area of Science:

  • Neuroscience
  • Medical Imaging
  • Neurology

Background:

  • Neuroimaging techniques assess brain structure, function, and protein deposition in Alzheimer's disease (AD).
  • While research on amnestic AD is extensive, atypical AD presentations (language, visual, dysexecutive, behavioral, motor) require further investigation for clinical trials.
  • Atypical AD patients, often younger with fewer co-pathologies, offer a purer model for studying disease progression and treatment effects.

Purpose of the Study:

  • To evaluate the utility of neuroimaging biomarkers for assessing disease progression in atypical Alzheimer's disease (AD) variants.
  • To determine optimal neuroimaging metrics and sample sizes for detecting treatment effects in clinical trials for language and visual AD.
  • To explore the potential of tau PET imaging and connectivity metrics as outcome measures in atypical AD.

Main Methods:

  • Analysis of brain atrophy rates, focusing on cortical measurements, in language and visual AD phenotypes.
  • Estimation of sample sizes needed to detect a 20% treatment effect based on inferior temporal atrophy rates.
  • Assessment of tau deposition patterns using PET imaging and evaluation of default mode network connectivity changes.

Main Results:

  • Cortical atrophy measurements are more effective than medial temporal ones for atypical AD.
  • Sample size estimates for detecting treatment effects were 113 patients for language AD and 100 for visual AD (per arm), based on inferior temporal atrophy.
  • Tau uptake patterns are relatively consistent across atypical AD phenotypes but vary in rate, potentially limiting utility in advanced disease. Connectivity declines, particularly in the default mode network, show variability influenced by age and tau burden.

Conclusions:

  • Neuroimaging biomarkers, including atrophy rates and tau deposition, are valuable for monitoring disease progression in atypical AD.
  • Heterogeneity in atrophy patterns, age, and disease stage must be considered in designing clinical trials for atypical AD.
  • Further research is needed to identify optimal biomarkers for tracking disease progression across the entire spectrum of Alzheimer's disease.