Identifying mixed Lewy body and Alzheimer’s disease pathologies using functional neuroimaging

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AbstractBackgroundLewy body dementia (LBD) and Alzheimer’s disease (AD) are the two most common neurodegenerative causes of dementia. Autopsy studies report many cases with these clinical diagnoses having mixed pathology with alpha‐synuclein, tau and amyloid proteinopathies. There is limited research in trying to distinguish these potential mixed pathology conditions prior to death. We used functional neuroimaging methods including FDG PET, amyloid PET, and DaTscan SPECT to evaluate clinically diagnosed subjects with dementia with Lewy bodies (DLB), AD and PD to investigate how often potential mixed pathologies could be present.MethodEighteensubjects (all Caucasian, male/female ratio 15:3) so far were recruited from Ohio State University Memory Disorder and Movement Disorder Clinics in this currently enrolling study. Subjects were diagnosed based on standard clinical criteria for DLB, PD and AD by fellowship trained cognitive and movement disorders faculty. Cognitive testing including Mini‐Mental State Examination (MMSE) and Self‐Administered Gerocognitive Examination (SAGE) were performed. Neuroimaging evaluations performed by neuroradiology faculty were blinded to clinical diagnosis.ResultNine subjects with clinical diagnosis of Lewy body disease (5 DLB and 4 PD) and nine subjects with clinical diagnosis AD were compared. The Lewy body subjects were 71.3 ± 7.4 years old, MMSE 22.3 ± 5.4, and SAGE 9.7 ± 4.8. AD subjects were 67.1 ± 9.6 years old, MMSE 18.6 ± 5.2, and SAGE 9.0 ± 5.2. One subject (11%) of the clinical AD cases showed mixed LBD and AD features, one subject (11%) of the clinical AD cases was negative for amyloid with normal DaTscan uptake, two subjects (40%) of the clinical DLB cases showed mixed LBD and AD features, one subject (20%) of the clinical DLB cases was positive for amyloid with normal DaTscan uptake, and all four subjects with clinical PD showed neuroimaging findings consistent with PD.ConclusionBased on functional neuroimaging, 21% of clinically diagnosed AD or DLB subjects had evidence of potential mixed pathologies and 14% were misdiagnosed. Although the sample size is small, functional neuroimaging studies revealed possibly incomplete or incorrect diagnoses in about one third of subjects clinically diagnosed by subspecialists using standard clinical diagnostic criteria. Larger studies are required to confirm these findings.