Characteristics of amnestic patients with hypometabolism patterns suggestive of Lewy body pathology

Abstract

A clinical diagnosis of Alzheimer’s disease dementia encompasses considerable pathological and clinical heterogeneity. While Alzheimer’s disease patients typically show a characteristic temporo-parietal pattern of glucose hypometabolism on FDG-PET imaging, previous studies identified a subset of patients showing a distinct posterior-occipital hypometabolism pattern associated with Lewy body pathology. Here, we aimed to improve the understanding of the clinical relevance of these posterior-occipital FDG-PET patterns suggestive of Lewy body pathology in patients with Alzheimer’s disease-like amnestic presentations. Our study included 1214 patients with clinical diagnoses of Alzheimer’s disease dementia (ADD; N=305) or amnestic mild cognitive impairment (aMCI, N=909) from the Alzheimer’s Disease Neuroimaging Initiative, who had FDG-PET scans available. Individual FDG-PET scans were classified as suggestive of Alzheimer’s (AD-like) or Lewy body (LB-like) pathology by using a logistic regression classifier previously trained on a separate set of patients with autopsy-confirmed Alzheimer’s disease or Lewy body pathology. AD- and LB-like subgroups were compared on Aβ- and tau-PET, domain-specific cognitive profiles (memory vs executive function performance), as well as the presence of hallucinations and their evolution over follow-up (≈6y for aMCI, ≈3y for ADD). 13.7% of the aMCI patients and 12.5% of the ADD patients were classified as LB-like. For both aMCI and ADD patients, the LB-like group showed significantly lower regional tau-PET burden than AD-like, but Aβ load was only significantly lower in the aMCI LB-like subgroup. LB- and AD-like subgroups did not significantly differ in global cognition (aMCI: d=0.15, p=0.16; ADD: d=0.02, p=0.90), but LB-like patients exhibited a more dysexecutive cognitive profile relative to the memory deficit (aMCI: d=0.35, p=0.01; ADD: d=0.85 p<0.001), and had a significantly higher risk of developing hallucinations over follow-up (aMCI: HR=1.8, 95% CI = [1.29, 3.04], p=0.02; ADD: HR=2.2, 95% CI = [1.53, 4.06] p=0.01). In summary, a sizeable group of clinically diagnosed ADD and aMCI patients exhibit posterior-occipital FDG-PET patterns typically associated with Lewy body pathology, and these also show less abnormal Alzheimer’s disease biomarkers as well as specific clinical features typically associated with dementia with Lewy bodies.