Objective:

To investigate how Lewy body (LB) pathology affects neurodegeneration patterns and clinical trajectories in amnestic patients with Alzheimer's disease (AD), emphasizing its significance for diagnosis and treatment.

Key Findings:

• AD+LB+ patients exhibited worse global cognition and faster cognitive decline compared to AD+LB−, indicating a need for tailored interventions.
• Both AD+LB+ and AD+LB− showed similar memory-predominant cognitive profiles and temporo-parietal hypometabolism, suggesting shared underlying mechanisms.
• AD−LB+ patients had less global impairment but a more dysexecutive and visuospatial cognitive profile with distinct posterior-occipital hypometabolism, which may inform treatment strategies.
• APOE4 positivity was similar in AD+LB+ and AD+LB− but significantly lower in AD−LB+, which could influence risk assessments.
• Patients with LB-like posterior-occipital hypometabolism had a higher risk of developing hallucinations, underscoring the importance of monitoring this symptom.

Interpretation:

LB co-pathology in AD is associated with more severe cognitive decline and hypometabolism, but does not alter the regional hypometabolic pattern or cognitive profile. Conversely, pure LB pathology leads to a distinct cognitive profile and imaging pattern, which has critical implications for diagnosis and treatment.

Limitations:

• Study limited to a specific cohort from the Alzheimer’s Disease Neuroimaging Initiative, which may not represent the broader population.
• Findings may not generalize to all populations with amnestic syndromes, and potential biases in the study population should be considered.

Conclusion:

The presence of LB pathology influences clinical phenotypes in amnestic patients, highlighting the need for accurate diagnosis and prognosis in these cases.