Objective: To examine the association between cognitive function in late-life and Parkinson’s disease (PD) neuropathology at death, including 1) neuron loss in the locus coeruleus (LC) and the nucleus basalis (NB), 2) substantia nigra (SN) neuron density, and 3) ascending Lewy pathology (LP) among autopsied decedents in the Honolulu-Asia Aging Study.

Background: Poor cognitive function is common in PD, most notably appearing as a prodromal feature or concomitant in PD dementia and dementia with Lewy bodies.  Whether associations also include underlying neuropathologic processes that lead to PD are uncertain.

Method: Data were collected from 1991 to 2012 in 791 men aged 72 to 103 years with later postmortem examinations.  Measurement of cognitive function was based on performance on the Cognitive Abilities Screening Instrument within 5 years of death.  Neuron loss in the LC and NB in decedent brains was defined as absent or present following standardized semi‑quantitative methods.  Neuron density (count/mm²) was measured in quadrants from transverse sections of the SN.  Presence of LP was based on staining for α-synuclein in multiple regions of the brain.

Results: Compared to men in the top quintile of cognitive function, those in the bottom quintile had more than a 2-fold excess in neuron loss in the LC and NB (33.5 vs 15.5% in the LC, p<0.001, and 23.1 vs 11.5% in the NB, p=0.010).  Within each SN quadrant, neuron density was positively associated with cognition.  Overall, SN density increased nearly 15% in the top vs bottom quintiles of cognitive function (18.0 vs 15.7/mm², p=0.002).  Cognitive function was also associated with ascending LP (p<0.001).  47.5% of men in the bottom quintile of cognitive function had LP in the SN and cerebral cortex (Braak stage ≥3) vs 27.6% in the top quintile.  Findings persisted for neuron loss in the LC, SN neuron density, and ascending LP after adjustment for age and other covariates, including PD and dementia with Lewy bodies.

Conclusion: Poor cognitive performance during life is associated with significant PD neuropathology at death.  Further studies of cognitive function and PD associated neuropathology are needed to better understand this relationship.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cognitive-function-in-late-life-and-parkinsons-disease-neuropathology-at-death/