To compare brain morphometry between amnestic older adults with and without Alzheimer’s pathology in Memory Clinics and investigate their relationship with memory performance and cerebrospinal fluid (CSF) biomarkers.

Amnestic syndrome of the hippocampal type (ASHT), characterized by episodic memory impairment, is a common presentation among patients evaluated in Memory Clinics. ASHT is a clinical criterion for typical Alzheimer’s Disease (AD), however, it can be found in other neurodegenerative disorders such as behavioral-variant Frontotemporal Lobar Degeneration (bvFTLD), Primary Age-Related Tauopathy (PART), or Limbic-predominant Age-related TDP-43 Encephalopathy (LATE). Automated brain morphometry represents a promising tool to support the diagnosis of AD, but it remains unclear how atrophy patterns differ between AD and non-AD patients with ASHT.

Brain morphometry of 92 consecutive Memory Clinic patients (72.5+/-6.8yo; 39% female) with Free and Cued Selective Recall Reminding Test total recall <40/48 was assessed with an automated algorithm and compared between AD and non-AD patients, as defined by Amyloid-β 42 and phosphorylated Tau CSF biomarkers. MRI volumes for regions of interest, including the hippocampus, were segmented using the research application MorphoBox and converted to Z-scores with respect to normative ranges. Multilinear models were used to investigate the relationship between memory performance, hippocampal atrophy, AD CSF biomarkers, and group classification.

Groups were comparable in demographics, clinical severity, Montreal Cognitive Assessment, and episodic memory. AD and non-AD patients presented comparable brain morphology both in terms of relative brain volumes (% of total intracranial volume) and Z-scores. Total recall score was associated to hippocampal volume independently from group classification (β = 0.44, 95% CI [0.19,0.67], p = 0.001).

In ASHT, hippocampal atrophy explains memory impairment irrespectively from AD pathology. Brain morphometry, including hippocampal volumes, is similar between AD and non-AD older adults with ASHT, underscoring the importance of including molecular biomarkers for the diagnosis of AD in memory clinics.