Parkinson’s Disease and Other Alzheimer’s Disease and Related Dementia Pathologies and the Progression of Parkinsonism in Older Adults

Article type: Research Article

Authors: Buchman, Aron S.^{a; b; *} | Yu, Lei^{a; b} | Oveisgharan, Shahram^{a; b} | Zammit, Andrea R.^{a; c} | Wang, Tianhao^{a; b} | Shulman, Joshua M.^d | VanderHorst, Veronique^e | Nag, Sukrit^f | Bennett, David A.^{a; b}

Affiliations: [a] Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA | [b] Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA | [c] Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA | [d] Department of Neurology and Center for Alzheimer’s and Neurodegenerative Diseases, Baylor College of Medicine and Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, USA | [e] Department of Neurology, Harvard Medical School, Boston, MA, USA | [f] Department of Pathology (Neuropathology), Rush University Medical Center, Chicago, IL, USA

Correspondence: [*] Correspondence to: Aron S. Buchman, MD, Rush Alzheimer’s Disease Center, 1750W; Harrison Street, Suite 1000, Chicago, IL 60612, USA. E-mail: [email protected].

Abstract: Background:The interrelationship of parkinsonism, Parkinson’s disease (PD) and other Alzheimer’s disease (AD) and Alzheimer’s disease and related dementias (ADRD) pathologies is unclear. Objective:We examined the progression of parkinsonian signs in adults with and without parkinsonism, and their underlying brain pathologies. Methods:Annual parkinsonian signs were based on a modified Unified Parkinson’s Disease Rating Scale. We used linear mixed effects models to compare the progression of parkinsonian signs in 3 groups categorized based on all available clinical evaluations: Group1 (never parkinsonism or clinical PD), Group2 (ever parkinsonism, but never clinical PD), Group3 (ever clinical PD). In decedents, we examined the progression of parkinsonian signs with PD and eight other AD/ADRD pathologies. Results:During average follow-up of 8 years, parkinsonian signs on average increased by 7.3% SD/year (N = 3,807). The progression of parkinsonian signs was slowest in Group1 (never parkinsonism or clinical PD), intermediate in Group2, and fastest in Group3. In decedents (n = 1,717) pathologic PD and cerebrovascular (CVD) pathologies were associated with a faster rate of progressive parkinsonian signs (all p values <0.05). However, pathologic PD was rare in adults without clinical PD (Group1, 5%; Group2, 7% versus Group3, 55%). Yet, 70% of adults in Group2 without pathologic PD showed one or more CVD pathologies. In Group2, adults with pathologic PD showed faster progression of parkinsonian signs compared with those without evidence of pathologic PD and their rate of progression was indistinguishable from adults with clinical PD. Conclusions:Parkinsonism in old age is more commonly related to cerebrovascular pathologies relative to pathologic PD and only a minority manifest prodromal PD.

Keywords: Alzheimer’s disease, Parkinson’s disease, parkinsonism, pathology

DOI: 10.3233/JAD-240593

Journal: Journal of Alzheimer's Disease, vol. 100, no. s1, pp. S197-S209, 2024