Clinical effects of Lewy body pathology in clinically unimpaired and cognitively impaired individuals – A prospective longitudinal study
Year: 2023
Type: article
Abstract: Background Aggregates of misfolded α‐synuclein are the underlying pathology of Lewy body (LB) disease. Little is known about the early effects of LB pathology in preclinical (i.e., pre‐symptomatic) individuals. Further, there is poor knowledge about the independent clinical effects of Lewy body (LB) pathology in patients with cognitive decline, especially when coexisting with Alzheimer’s disease (AD) pathology. Method Here, we examined the effects of LB pathology using a cerebrospinal fluid α‐synuclein seeding aggregation assay in 1,182 cognitively and neurologically unimpaired participants as well as 882 participants with mild cognitive impairment or dementia from the BioFINDER‐1 and BioFINDER‐2 studies. Result In clinically unimpaired individuals, we found that 8% were LB‐positive, 26% Aβ‐positive (12% of those were also LB‐positive), and 16% tau‐positive. LB pathology had independent and significant negative effects on cross‐sectional and longitudinal global cognition and memory. These were similar in magnitude to the effects of tau pathology and more pronounced than those of Aβ pathology. Participants with both LB and AD (Aβ and tau) pathology exhibited faster cognitive decline than those with just LB or AD pathology. LB, but not AD, pathology was associated with reduced sense of smell. In cognitively impaired individuals, we found that 23% of participants had LB pathology, of whom only 32% fulfilled clinical criteria of Parkinson’s disease or dementia with Lewy bodies, and 54% exhibited AD pathology (amyloid‐β+ and tau+). Within the LB‐positive group, 48% also had AD‐pathology. In the AD‐positive group, 17% of patients with mild cognitive impairment and 24% of those with dementia were also LB‐positive. LB pathology was associated with worse attention/executive, visuospatial, and motor function independently of AD pathology. Moreover, LB pathology was also independently associated with a faster longitudinal decline in all examined cognitive functions. Conclusion This study highlights the cognitive effects of LB pathology, independent from AD pathology, in clinically unimpaired individuals, which will be important to consider for prognosis and design of both preclinical AD and LB disease trials. Further, analyzing LB status, in addition to amyloid‐β and tau, in cognitively impaired individuals provides a better precision medicine approach identifying patient subgroups with different clinical trajectories.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.072852
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4390194756