Objective: Our objective is to examine the association of mid-life smoking with post mortem substantia nigra (SN) neuron density in the presence and absence of Lewy pathology (LP) in the Kuakini Honolulu-Asia Aging Study (HAAS).
Background: Cigarette smoking is one of the strongest environmental factors related to lower risk of Parkinson’s disease (PD). LP is considered a benchmark of neuropathologic processes leading to PD, but LP can also occur in brains without PD. Whether smoking has a modifying effect on this relationship is unknown. By evaluating the relationship of smoking with SN neuron density in individuals with and without LP, we hope to better understand the inverse association between smoking and PD.
Method: SN neuron counts were performed on single transverse caudal midbrain sections from 762 deceased HAAS participants with autopsies performed from 1992-2008. Quadrant areas within the SN were determined and quadrant density reported as neurons/mm2. Information on smoking was obtained from 1965 to 1968 when participants were aged 46 to 67 years (mean age 53). Presence of LP was also assessed.
Results: Average age at death was 87 years (range 73-106). Total SN neuron density was 9.0% higher in smokers versus nonsmokers (17.4 vs 16.0/mm2, p=0.005). The relationship was strongest in the ventromedial quadrant (p<0.001). When stratified by absence and presence of LP, total neuron density had no relationship with smoking among brains without LP (p=0.217). Among brains with LP, excess neuron density in smokers vs nonsmokers was significantly greater in each SN quadrant. Excesses ranged from 19.0% for the dorsomedial quadrant (p=0.024) to 25.2% in the ventrolateral quadrant (p=0.032). The association that smoking had with total neuron density was significantly different in the presence versus absence of LP (p=0.017). Findings persisted after adjustment for age at death and other covariates.
Conclusion: Mid-life cigarette smoking was associated with higher neuron density in the substantia nigra at death among brains with LP. Whether smoking offers a partial explanation for why decedents with LP do not always progress to PD warrants further study.
To cite this abstract in AMA style:
G. Ross, R. Abbott, H. Petrovitch, J. Duda, J. Uyehara-Lock, K. Masaki, C. Tanner. Smoking and Substantia Nigra Neuron Density in the Presence and Absence of Lewy Pathology [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/smoking-and-substantia-nigra-neuron-density-in-the-presence-and-absence-of-lewy-pathology/. Accessed May 15, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/smoking-and-substantia-nigra-neuron-density-in-the-presence-and-absence-of-lewy-pathology/