MCI in Early Parkinson's Disease Predicts Dementia

Pauline Anderson

April 04, 2013

Having mild cognitive impairment (MCI) when diagnosed with Parkinson's disease (PD) predicts progression to dementia, a new study suggests.

The research showed that more than 25% of patients who had MCI when PD was diagnosed developed dementia within 3 years compared with less than 1% of patients with newly diagnosed PD who did not have MCI.

"Cognitive testing should be performed in the early phase of PD, even at the time of PD diagnosis, to detect patients with MCI who need closer monitoring of cognitive status during follow-up," said lead author Kenn Freddy Pedersen, MD, PhD, consultant neurologist, Department of Neurology and Memory Clinic, and researcher, Norwegian Centre for Movement Disorders, Stavanger University Hospital, Norway.

Identifying patients with PD who are at high risk of developing dementia will be helpful for recruiting for future prevention trials, as well as to target treatment once relevant interventions become available, said Dr. Pedersen.

The study was published online March 25 in JAMA Neurology.

MCI Criteria

The analysis included 182 participants in the Norwegian ParkWest project, a population-based study of the incidence, neurobiology, and prognosis of PD. Researchers followed this cohort of patients with newly diagnosed PD without dementia for 3 years, and the patients underwent regular neurocognitive testing.

Dr. Kenn Freddy Pedersen

This was the first time that a study examining the longitudinal course of MCI used newly proposed consensus diagnostic criteria developed by the Movement Disorders Society Task Force. The study patients had to meet the following criteria to be diagnosed with PD-MCI:

  1. Objective cognitive deficits (at least 2 neuropsychological test scores falling at least 1.5 standard deviations below the mean value of appropriate norms);

  2. Subjective cognitive problems (a score greater than 3.0 on the Informant Questionnaire on Cognitive Decline in the Elderly, or a score of at least 1 on item 1, intellectual impairment, of the United Parkinson's Disease Rating Scale part 1 [mentation, behavior, and mood section]);

  3. No functional impairment in basic activities of living caused by cognitive dysfunction; and

  4. No dementia.

The study also assessed possible or probable PD dementia (PDD), a slowly progressing dementia syndrome that develops within the context of established PD. According to Dr. Pedersen, PDD is impairment in more than 1 cognitive domain, representing a decline from premorbid level, and with deficits severe enough to impair daily life, independent of impairment caused by motor and autonomic functions.

In contrast to patients with Alzheimer's disease (AD), who typically present with prominent memory deficits but not fluctuating attention, those with PDD and dementia with Lewy bodies may have deficits in attention, as well as in visuospatial and executive function, with less memory impairment, said Dr. Pedersen.

Incident Dementia

Of 37 patients in the study with MCI at baseline, 10 (27.0%) developed incident dementia within 3 years of follow-up, compared with only 1 of 145 (0.7%) of those without MCI. Of those with MCI status at both baseline and 1 year, 45.5% had developed PDD at 3 years.

The relative risk (RR) for progression to dementia during follow-up in patients with MCI vs non-MCI at baseline was 39.2 (95% confidence interval, 5.2 - 296.5; P < .001).

The diagnosis of MCI was highly predictive. "Ten of 11 (91%) patients who developed PDD during the 3-year follow-up were categorized as MCI at their first evaluation — at the time that PD was diagnosed — and before initiation of dopaminergic treatment," explained Dr. Pedersen. "The corresponding positive predictive value was 27% (the proportion of PD patients with MCI at baseline who progressed to dementia), but this proportion is likely to increase with even longer follow-up."

The diagnosis also had negative predictive value. Only 1 of 145 patients without MCI at baseline progressed to PDD during the study period. "This patient had no MCI at 1-year follow-up, but progressed to PDD during the next 2 years," said Dr. Pedersen. "This indicates that a small proportion of patients may have a more malignant course, characterized by prominent cognitive decline leading to full-blown dementia in just a couple of years."

He noted that neuropsychological testing was not performed at the 2-year follow-up, but if it had been, "it probably would have identified this patient as MCI."

The finding of a 9% annual progression rate of MCI to dementia in early PD is consistent with studies in non-PD populations. These studies have reported annual progression rates, mainly in AD, of 6% to 10% in population-based cohorts and 10% to 15% in clinic-based samples, said Dr. Pedersen.

Although the researchers didn't perform MCI subtyping (eg, amnestic vs nonamnestic), they did find that patients with MCI who converted to dementia had more deficits in attention and verbal memory at baseline than those who didn't progress to dementia.

The study results are consistent with previous research showing that frontal/executive and verbal memory deficits are associated with the development of PDD, although other studies have found that visuospatial dysfunction predicts incident dementia in PD, said Dr. Pedersen.

"These inconsistencies may reflect different definitions of cognitive impairment and PDD, differences in sample characteristics, or biological heterogeneity. In addition, individual differences in cognitive reserve, for example, higher educational level, could also account for some of these inconsistencies."

He added that the small sample size of the MCI subgroups, along with the relatively short follow-up, does not allow for any firm conclusions about which patients with MCI convert to dementia.

Cognitive Reversion?

Interestingly, a sizable number of patients in the study (9.1%) reverted from PD-MCI at both baseline and 1 year to normal cognition. Dr. Pedersen pointed out that it's possible that some of these patients would progress to PDD later. "Longer follow-up periods are needed to determine whether these patients are prone to re-convert to MCI and possibly progress to dementia over a prolonged period."

Improved cognition after initiation of dopaminergic treatment in drug-naive patients with PD may have contributed to the reversion in this study, he added.

The issue of stability of PD-MCI over time is an important one, according to an accompanying editorial. http://archneur.jamanetwork.com/article.aspx?articleid=1671737" Brian J. Copeland, MD, Movement Disorders Section, Department of Neurology, and Mya C. Schiess, MD, Movement Disorders and Neurodegenerative Diseases Fellowship Program, Department of Neurology, University of Texas Medical School at Houston, stressed that "any enthusiasm over the predictive value of the diagnosis must be tempered with that in mind."

Dr. Copeland and Dr. Schiess point out that most patients in the study did not develop PD-MCI (about 80%) or PDD (more than 90%) in the 3 years of follow-up. "Presumably, these numbers would decrease with longer follow-up."

"Using multiple easily accessible clinical measures such as Unified Parkinson Disease Rating Scale motor scores and serial neurocognitive testing that includes measures from all 5 cognitive domains, along with the identification of associated factors such as increased age and the presence of visual hallucinations and REM sleep behavior disorder, will greatly improve our predictive abilities," they conclude.

In offering her own comments, Jennifer G. Goldman, MD, MS, associate professor, Section of Parkinson Disease and Movement Disorders, Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, said that longitudinal studies of patients with early PD followed prospectively, such as this one, are important to better understand the progression of the disease. This, she said, is particularly true for the nonmotor aspects of the disease, such as cognition.

"Such features have not been as readily studied, or even identified as problems when mild and early in the course of PD, so that, in and of itself is a valuable part of this study," she told Medscape Medical News.

Dr. Goldman expects the study will promote an increased recognition that cognitive deficits in PD are not just a phenomenon of advanced disease and might even spur more cognitive testing in the clinic or with formal neuropsychological assessments in patients with newly diagnosed PD.

She was also pleased to see that the diagnostic criteria, proposed by the Movement Disorder Society PD-MCI Task Force and to which she contributed, have clinical and research applications.

"It's exciting to see that they can help us understand the concept of MCI in PD. Now, we will be more likely to identify PD-MCI in a more uniform way, across multiple sectors and multiple studies, and understand its stability or progression to dementia."

The Norwegian ParkWest study was supported by grants from the Western Norway Regional Health Authority, the Research Council of Norway, and the Norwegian Parkinson Disease Association. Dr. Pedersen has received speaker honoraria from H. Lundbeck A/S.

JAMA Neurol. Published online March 25, 2013. Abstract Editorial

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