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Clinical Manifestations.

Panagiotis Georgios Passias1, Roberto Vicidomini1, Rifa Sanjida Punnota1

  • 1Imperial College London, London, Greater London, United Kingdom.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

A significant portion of Alzheimer's Disease patients show parietal atrophy, not medial temporal lobe atrophy, especially in early stages. This parietal variant has distinct biological and clinical features, suggesting tau pathology drives differences.

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Area of Science:

  • Neuroscience
  • Neurology
  • Radiology

Background:

  • Medial Temporal Lobe (MTL) neurodegeneration is typical in Alzheimer's Disease (AD).
  • Some AD patients exhibit cognitive impairment without MTL involvement, with unclear cortical degeneration patterns.
  • This study investigates early atrophy patterns beyond the MTL in the AD trajectory.

Purpose of the Study:

  • To evaluate if regional atrophy can initiate in areas other than the MTL in Alzheimer's Disease.
  • To characterize the distinct features of patients with parietal atrophy compared to those with MTL atrophy.

Main Methods:

  • Analysis of 1124 participants from the ADNI database.
  • Collected Cerebrospinal Fluid (CSF) biomarkers (Aβ42, Aβ40, tau, ptau) and region of interest volumes.
  • Utilized PET imaging (Tau, Amyloid, FDG) to assess Standardized Uptake Value Ratios and identify early lobar volume changes.

Main Results:

  • 25% of patients presented with parietal atrophy, a higher proportion in early disease stages (SMC, EMCI).
  • The parietal group showed lower ADAS-Cog-13 scores but higher MMSE scores.
  • Parietal atrophy was associated with reduced ptau/tau and ptau/Aβ42 ratios, higher hippocampal amyloid deposition, and lower MTL tau levels.

Conclusions:

  • Isolated parietal atrophy occurs in 25% of memory-impaired patients, presenting unique biological, imaging, and clinical characteristics.
  • Lower tau accumulation in the parietal variant may explain milder cognitive impairment, highlighting tau's role in phenotypic differences.
  • Precise subcategorization of cognitive impairment patients is crucial for targeted therapy selection.