The following is a summary of “Differential Vulnerability of Hippocampal Subfields to Amyloid and Tau Deposition in the Lewy Body Diseases,” published in the May 2024 issue of Neurology by Ye et al.
Alzheimer’s disease (AD) proteins (β-amyloid and tau) are often found alongside Lewy body diseases (LBD), such as dementia with Lewy bodies (DLB) and Parkinson’s disease (PD), affecting different parts of the hippocampus.
Researchers started a retrospective study to investigate whether AD proteins influence hippocampal subregion shrinkage and cognitive decline in LBD.
They involved participants who underwent neuropsychological testing and 3T-MRI with hippocampal segmentation using FreeSurferV7. PiB-PET and flortaucipir-PET imaging measured comorbid β-amyloid (A) and tau (T). The association of functional cognition, β-amyloid, and tau loads with hippocampal subregion volume was evaluated. Mediation analysis examined the contribution of subregion volumes to the relationship of AD-related deposits on functional cognition. Mixed-effects models assessed the impact of AD-related deposits on the rate of subregion atrophy.
The results showed 103 participants (mean age: 70.3 years; 37.3% female), 52 had LBD with impaired cognition (LBD-I), 26 had normal cognition (LBD-N), and 25 were A− HCs. The LBD-I participants had reduced volumes in hippocampal subregions prone to AD copathologies, subiculum (F = 6.9, P=0.002), presubiculum (F = 7.3, P=0.001), and parasubiculum (F = 5.9, P=0.004) compared to LBD-N and HC. CA2/3 volumes, susceptible to Lewy pathology, were preserved. In LBD-I, smaller CA1, subiculum, and presubiculum volumes correlated with greater cognitive impairment (all P<0.05). Subiculum volume was reduced in A+T+ but not A−T− participants compared to HC (F = 2.62, P=0.043). Reduced subiculum volume mediated amyloid’s impact on cognition (0.12, 95% CI: 0.005 to 0.26, P=0.040). In 26 participants evaluated longitudinally, baseline tau deposition predicted faster atrophy in CA1 (P=0.021) and subiculum (P=0.002).
Investigators concluded that, in LBD, subiculum atrophy was linked to both cognitive decline and AD markers, with tau accelerating shrinkage.
Source: neurology.org/doi/10.1212/WNL.0000000000209460
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