Impact of Incidental Synucleinopathy in Mild Cognitive Impairment due to Alzheimer’s Disease
Jahnavi Shriram1, Michael Malek-Ahmadi2, Marwan Sabbagh3
1University of Arizona College of Medicine, Phoenix, 2Banner Alzheimer's Institute, 3Barrow Neurological Institute
Objective:
We sought to determine whether incidental LB pathology in patients with MCI due to AD is associated
with faster rate of cognitive decline in the pre-clinical phase compared to MCI controls without mixed
pathology.
Background:
The hallmark neuropathologies of Alzheimer’s disease include amyloid plaques and tau neurofibrillary
tangles. Recent evidence suggests that incidental co-occurrence of Lewy Bodies (LB), correlates with
accelerated disease progression in AD patients. It is unclear whether this effect is also exerted in the pre-dementia phase of AD, in patients with mild cognitive impairment (MCI).
Design/Methods:
6654 subjects were identified from the National Alzheimer’s Coordinating Center (NACC) database
with autopsy-confirmed AD pathology who remained in the MCI, (Albert 2011 criteria), throughout
their ADRC annual assessments. 89 subjects had co-incident Lewy Bodies while the remaining 6565
controls lacked any mixed pathology. We utilized a repeated measures longitudinal analysis of
multiple cognitive performance markers to determine whether decline in scores occurred at a
greater rate in the synucleinopathy subjects.
Results:
For MCI-LB, mean age and education was (72.2± 8.9 and 15.7± 5.8). For MCI+LB subjects mean age
and education was (77..9± 7.8 and 16.6± 6.8). 44 MCI +LB subjects and 2555 MCI -LB had complete
data for MMSE scores and were included in the corresponding analysis and a subset had complete
data for the Weschler Adult Intelligence Scale (WAIS) Digit Symbols test. The rate of decline in
overall MMSE scores and WAIS-R Digit Symbols test did not differ between the two groups.
Conclusions:
While mixed LB pathology correlates with a greater rate of cognitive decline in patients with AD,
our results do not suggest that co-incident LB accelerates decline in subjects remaining in MCI. To
further characterize the effect of mixed pathology on AD disease course, next steps may include
investigating whether co-occurrent LB pathology hastens progression to meeting criteria for AD
diagnosis.