Alzheimer’s may play limited role in early Parkinson’s cognitive problems

Alzheimer’s-related brain changes may not be a major contributor to earlier cognitive problems in people with Parkinson’s disease who have not developed dementia, a new study suggests.

Researchers found that blood levels of phosphorylated tau-217 (p-tau217), a blood marker of early Alzheimer’s disease, were not clearly associated with cognitive impairment. The findings suggest that early cognitive changes in Parkinson’s may primarily result from the disease itself, with coexisting Alzheimer’s-related changes potentially playing a larger role in people who develop dementia, the researchers noted.

The researchers cautioned, however, that p-tau217 may have limited sensitivity for detecting Alzheimer’s-related pathology in people with Parkinson’s. Further studies using brain imaging are needed to validate the findings.

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The study, “Association Between Plasma Phosphorylated Tau-217 and Cognition in Parkinson’s Disease,” was published in Movement Disorders.

Cognitive impairment affects about one in 10 people in the early stages of Parkinson’s, and becomes more common as the disease progresses, affecting up to three-quarters of people in later stages. Its timing and severity vary considerably from person to person.

Studies examining brain tissue of people with Parkinson’s after their death have found Alzheimer’s-related changes, including accumulations of amyloid-beta protein and neurofibrillary tangles of tau protein, in up to 40% of those who developed Parkinson’s-related dementia. Brain imaging studies have also linked these changes to poorer cognitive function.

However, most of this research has “focused on Parkinson’s-related dementia, the later stage of [Parkinson’s]-associated cognitive impairment, leaving open questions about the degree to which [Alzheimer’s-related disease] contributes to earlier/milder cognitive impairment in [Parkinson’s],” the researchers wrote.

To help answer that question, researchers in Canada examined whether blood p-tau217 levels were associated with earlier cognitive impairment in people with Parkinson’s who had not developed dementia.

The team analyzed blood p-tau217 measurements from 165 people with Parkinson’s who did not have dementia and 58 healthy controls enrolled through the Quebec Parkinson Network, a registry of people with Parkinson’s and healthy volunteers.

The analysis included participants who had completed a comprehensive battery of neuropsychological tests or the Montreal Cognitive Assessment (MoCA), a commonly used screening test for cognitive impairment. The neuropsychological tests evaluated attention and working memory, executive function, memory, language, and visuospatial abilities. Information on self-reported cognitive difficulties was available for 157 participants with Parkinson’s.

Blood marker shows no clear link to cognitive performance

Overall, blood levels of p-tau217 were similar in people with Parkinson’s and healthy participants. Although people with Parkinson’s performed worse than healthy adults on the MoCA and several neuropsychological measures, p-tau217 levels showed no clear link to overall cognitive impairment, cognitive performance, or self-reported cognitive difficulties.

Among the 84 participants with Parkinson’s whose APOE4 status was available, people carrying the APOE4 genetic variant, a genetic risk factor for Alzheimer’s, had higher p-tau217 levels than noncarriers. However, APOE4 status was not associated with cognitive performance, nor did it influence the relationship between p-tau217 levels and cognition.

“Our study found that [blood] p-tau217 was not clearly associated with cognitive impairment in the earlier stages of [Parkinson’s],” the researchers concluded. “Early cognitive impairment in [Parkinson’s] may primarily result from [Parkinson’s]-related mechanisms, with the effects of [coexisting Alzheimer’s-related disease] being more evident only in those who develop dementia.”

The team, however, cautioned that although “p-tau217 is a sensitive marker” of early Alzheimer’s disease, its ability to detect Alzheimer’s-related changes in people with Parkinson’s still needs to be confirmed using brain imaging that can detect amyloid-beta and tau accumulation.

Further studies are needed to clarify how Alzheimer’s-related pathology contributes to earlier cognitive impairment in Parkinson’s. Meanwhile, the findings underscore the need “to consider both [Alzheimer’s]-related and [Parkinson’s]-specific processes when investigating cognitive impairment in [Parkinson’s],” the researchers wrote.