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Parkinson's Dementia May Be Less Common Than Once Thought

<ѻý class="mpt-content-deck">— Progression from normal cognition to dementia may have a fairly long window of time
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Key Takeaways

  • Parkinson's disease dementia may occur less frequently than previously thought.
  • The estimated risk of dementia increased with disease duration.
  • Age, male sex, and lower educational level raised dementia risk.

Dementia in Parkinson's disease occurred less frequently or later in the disease course than previously reported, data from two ongoing prospective cohorts showed.

The study, reported in by Daniel Weintraub, MD, of the University of Pennsylvania (Penn) in Philadelphia, and co-authors, assessed longitudinal information from the international Parkinson's Progression Markers Initiative (PPMI) cohort and a long-standing Parkinson's research cohort at Penn.

When data from both cohorts were combined, the estimated risk of dementia by duration of Parkinson's disease was:

  • 3%-12% at year 5
  • 9%-27% at year 10
  • 50% at year 15
  • 74% at year 20

It's often cited that dementia of Parkinson's patients, Weintraub and colleagues noted. However, studies reporting these rates were published over 15 years ago, had relatively , had high ages at enrollment, or didn't have dementia diagnoses made by a study investigator.

The findings from the PPMI and Penn cohorts show "more hopeful estimates" of Parkinson's dementia risk, suggesting a longer window to intervene and possibly delay cognitive decline, Weintraub said.

"The progression from normal cognition to dementia in Parkinson's disease may occur less commonly, or over a longer period of time, than commonly thought," he told ѻý.

"It's important for both clinicians, and patients and their families, to have a sense of the expected long-term course of cognition in Parkinson's disease to help with clinical management and life planning," Weintraub continued. "It's also important to screen Parkinson's patients routinely for cognitive abilities, starting at time of diagnosis."

The PPMI enrolled de novo, untreated participants with Parkinson's disease, while the Penn study was a convenience cohort from a large clinical center.

In the PPMI group, 417 Parkinson's patients were tested with an annual cognitive battery and a site investigator made a cognitive diagnosis. Mean baseline age was about 62 years, and 65% were men. Mean Parkinson's duration at baseline was 0.6 years.

At Penn, a comprehensive cognitive battery was administered annually for the first 4 years, then biennially. Cognitive diagnoses were made by expert consensus, with patients assigned a diagnosis of normal cognition, mild cognitive impairment, or dementia. The Penn sample included 389 Parkinson's patients with a mean baseline age of about 69 years; 67% were men. Mean Parkinson's duration at baseline was 6.3 years.

The primary endpoint was a cognitive diagnosis of dementia. In the PPMI, a Montreal Cognitive Assessment () score under 21 and a Movement Disorder Society-Unified Parkinson's Disease Rating Scale () Part I cognition score of 3 or higher were secondary endpoints. The researchers fit interval-censored survival curves for time from Parkinson's diagnosis to dementia diagnosis in each cohort.

At year 10, the PPMI cohort had an estimated probability of dementia of 9% by site investigator diagnosis, 15% by MoCA score, and 12% by MDS-UPDRS Part I cognition score.

In the Penn cohort, 184 of 389 participants (47.3%) were eventually diagnosed with dementia. The interval-censored curve for the Penn cohort had a median time to dementia of 15.2 years. At 10 years of disease duration, the estimated probability of dementia was 27%. At 15 years, it was 50%, and at 20 years it was 74%.

Factors that increased dementia risk in the Penn study included age at Parkinson's diagnosis, being male, and having a lower level of education.

The median time from Parkinson's diagnosis to dementia diagnosis in the Penn cohort was 19.4 years for patients younger than 56, 14.6 years for those ages 56 to 70, and 9.2 years for those older than 70. The median time from Parkinson's diagnosis to dementia diagnosis varied significantly by sex: it was 19.4 years for women and 13.3 years for men. Overall, 58.8% of those with less than 13 years of education, and 45.6% of those with 13 or more years of education, were diagnosed with dementia.

In both studies, participants were highly educated, and more than 90% were white. These Parkinson's patients were recruited to participate in research studies and may not represent the general population.

  • Judy George covers neurology and neuroscience news for ѻý, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more.

Disclosures

The Parkinson's Progression Markers Initiative (PPMI) is a public-private partnership funded by the Michael J. Fox Foundation for Parkinson's Research and its partners, which include several pharmaceutical companies.

The Penn data were obtained as part of a National Institute on Aging grant.

Weintraub reported receiving funding from the Michael J. Fox Foundation, the Alzheimer's Therapeutic Research Initiative, the Alzheimer's Disease Cooperative Study, the International Parkinson and Movement Disorder Society, the NIH, the Parkinson's Foundation, the U.S. Department of Veterans Affairs, and Acadia Pharmaceuticals. He has received consulting fees from Acadia Pharmaceuticals, Alkahest, Aptinyx, Cerevel Therapeutics, the CHDI Foundation, Clintrex LLC (Otsuka), EcoR1 Capital, Eisai, Ferring, Gray Matter Technologies, Great Lake Neurotechnologies, Intra-Cellular Therapies, Janssen, Merck, Sage, Scion, and Signant Health, and receives license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS.

Co-authors reported relationships with pharmaceutical companies, nonprofit agencies, academic institutions, and others.

Primary Source

Neurology

Gallagher J, et al "Long-term dementia risk in Parkinson disease" Neurology 2024; DOI: 10.1212/WNL.0000000000209699.