Impact of Incidental Synucleinopathy in Mild Cognitive Impairment due to Alzheimer’s Disease (P7-6.003)

Abstract

<h3>Objective:</h3> 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. <h3>Background:</h3> 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). <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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. <h3>Conclusions:</h3> 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. <b>Disclosure:</b> Ms. Shriram has nothing to disclose. Michael Malek-Ahmadi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Signant Health. Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genetech=Roche. Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Synaptogenix. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant Health. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for T3D. Dr. Sabbagh has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for EIP Pharma. Dr. Sabbagh has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Quince-Cortexyme. Dr. Sabbagh has stock in Neurotau. Dr. Sabbagh has stock in Seq Biomarque. Dr. Sabbagh has stock in uMethod Health. Dr. Sabbagh has stock in Athira. Dr. Sabbagh has stock in Lighthouse Pharmaceuticals. Dr. Sabbagh has stock in Alzheom. The institution of Dr. Sabbagh has received research support from NIH. The institution of Dr. Sabbagh has received research support from ADDF. Dr. Sabbagh has received publishing royalties from a publication relating to health care.