Can Alzheimer's disease (AD) be present without hippocampal atrophy on Magnetic Resonance Imaging (MRI)?

Alzheimer's Disease Can Occur Without Hippocampal Atrophy on MRI

Yes, Alzheimer's disease can definitely be present without hippocampal atrophy on MRI. According to recent evidence, approximately 60% of patients with confirmed Alzheimer's disease do not show hippocampal atrophy when evaluated with clinical MRI methods 1.

Diagnostic Implications of Normal Hippocampal Volume in AD

Biomarker Framework

• While hippocampal atrophy is a recognized biomarker of neurodegeneration in AD, it is not required for diagnosis 2
• The Alzheimer's Association guidelines classify biomarkers into two main categories:
  • Biomarkers of amyloid-beta (Aβ) protein deposition (low CSF Aβ42 and positive PET amyloid imaging)
  • Biomarkers of downstream neuronal degeneration or injury (including hippocampal atrophy) 2

Clinical Presentation Without Hippocampal Atrophy

Patients with AD who lack hippocampal atrophy often present with:

• Younger age at onset 1
• Less impairment on global cognitive measures 1
• Better preserved memory function 1
• More prominent deficits in:
  • Executive function
  • Visuospatial abilities
  • Semantic fluency 1
• Higher likelihood of presenting with non-amnestic AD phenotypes 1

Diagnostic Approach When Hippocampal Atrophy is Absent

When hippocampal atrophy is not evident but AD is suspected:

1. Consider molecular biomarkers:

   • Amyloid PET imaging to detect brain amyloid deposition 2
   • CSF analysis for Aβ42 and tau proteins 2

2. Evaluate other imaging markers:

   • FDG-PET to assess for characteristic hypometabolism in temporoparietal regions 2, 3
   • Structural MRI to look for cortical thinning in other regions (medial, basal, lateral temporal lobe and medial parietal cortex) 2

3. Assess for atypical presentations:

   • Non-amnestic variants of AD may present with normal hippocampal volumes 1

Progression and Monitoring

• Disease progression rates do not differ significantly between AD patients with and without hippocampal atrophy 1
• Longitudinal monitoring may eventually reveal developing atrophy in initially normal hippocampi 4, 5
• Hippocampal atrophy rates (rather than baseline volumes) may be more sensitive for predicting progression from MCI to AD 4

Clinical Pitfalls to Avoid

1. Do not rule out AD based solely on normal hippocampal volumes

   • Absence of hippocampal atrophy does not exclude AD diagnosis 1

2. Consider age-related factors

   • Younger patients with AD are less likely to show hippocampal atrophy 1

3. Recognize limitations of visual assessment

   • Quantitative volumetric measurements are more sensitive than visual assessment for detecting subtle atrophy 6

4. Avoid over-reliance on structural imaging alone

   • Functional and molecular imaging provide complementary information 2

5. Remember that hippocampal atrophy is not specific to AD

   • It can occur in other conditions including hippocampal sclerosis, frontotemporal degeneration, and tangle-only degeneration 7

In conclusion, while hippocampal atrophy is a valuable biomarker in AD diagnosis, its absence does not rule out the disease. Molecular biomarkers and comprehensive cognitive assessment remain essential for accurate diagnosis, especially in patients with normal hippocampal volumes on MRI.