Website Edition: February/March 2010

Editor's Choice Article and Review

Movement Disorders
Volume 24, Issue 16, Pages 2391-2397

Apathy may herald cognitive decline and dementia in Parkinson's disease
Kathy Dujardin, PhD ¹ ²*, Pascal Sockeel, PhD ¹ ³, Marie Delliaux, MPsych ², Alain Destée, MD, PhD ¹ ², Luc Defebvre, MD, PhD ¹ ²*

¹ Université Lille Nord de France, France
² Neurology and Movement Disorders Unit, Faculty of Medicine and University Medical Center, Lille, France
³ Psychology Department, Villeneuve d'Ascq, France

E-mail: Kathy Dujardin (k-dujardin@chru-lille.fr)

*Correspondence to Kathy Dujardin, Neurologie et Pathologie du Mouvement, Neurologie A, Hôpital Salengro, Centre Hospitalier Universitaire, F-59037 Lille Cedex, France

Potential conflict of interest: Nothing to report.

Abstract

Apathy is usually defined as a lack of motivation. It may occur as part of another disorder (notably depression and dementia) or as an isolated syndrome. In Parkinson's disease (PD), apathy is common and several studies have reported an association between this condition and more severe cognitive symptoms, such as executive dysfunction. However, this association has not been thoroughly investigated. The aim of this study (in nondepressed, nondemented PD patients) was to examine whether or not cognitive decline and/or dementia occurred more frequently in apathetic subjects than in nonapathetic subjects. Forty consecutive PD patients participated in the study (20 with apathy and 20 without). None of the subjects were either demented or depressed at the time of study entry. The patients' cognitive functions were extensively assessed twice: at study entry and after an 18-month follow-up period. At study entry, the apathetic PD patients had significantly lower global cognitive status and executive function scores than the nonapathetic subjects. After a median period of 18 months, the rate of conversion to dementia was found to be significantly higher in the apathetic group than in the nonapathetic group (8 of 20 and 1 of 20, respectively). Even in nondemented patients, the decrease over time in cognitive performance (mainly executive function but also memory impairment) was significantly greater in apathetic subjects than in nonapathetic subjects. These findings suggest that in nondemented, nondepressed PD patients, apathy may be a predictive factor for dementia and cognitive decline over time.

© 2009 Movement Disorder Society

Received: 22 May 2009; Accepted: 19 September 2009

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Podcast Summary and Review by Lindsey Kirsch-Darrow, MS, and Dawn Bowers, PhD

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This is a review and critique of the study entitled: "Apathy May Herald Cognitive Decline and Dementia in Parkinson's disease" published in Movement Disorders, volume 24, number 16, first published online in November 2009. The study's lead author is Kathy Dujardin from the University of Lille, France.

This is a well written paper on an important and clinically relevant topic. Authors provide important data assessing group differences between apathetic and nonapathetic PD groups at baseline and 18 months later. In the introduction, authors point out that apathy has been associated with worsened cognitive status-especially executive functioning. They note, however, that until their study, all have been correlational in nature. This is the first study to examine whether apathy at a baseline time-point can predict cognitive decline later in the course of the disease.

Forty consecutive non-demented, non-depressed PD patients were assessed at study entry. Patients were divided into Apathetic and Non-apathetic groups based on their scores on the Lille Apathy Rating Scale (over -17). Twenty patients were in each group. Demographic, disease variables, the Montgomery and Asberg Depression Rating Scale (MADRS) and the Lille Apathy Rating Scale (LARS) were collected. Cognitive variables were also obtained, and included the Mattis Dementia Rating Scale, and tests in several cognitive domains including memory, attention and executive functioning. Memory was tested using Grober and Bushke's word list learning task and Digit span forwards and backwards (working memory). Attention was measured using the oral version of the Symbol Digit Modalities test. Executive Functioning was tested using the Stroop interference condition, an oral version of Trail Making test, and verbal fluency tasks involving phonemic, semantic, and alternating fluency conditions. The two groups of Apathetic and Non-apathetic patients were assessed at baseline and then a median of 18 months later. The second testing ranged from 11 to 24 months after the first assessment.

MANOVAs were used to analyze group differences. A chi squared test was used to analyze the frequency of conversion to dementia between groups.

Results indicated that Apathetic and Non-apathetic groups differed at baseline along several dimensions. The Apathetic group had worse motor severity, higher depression scores, and higher apathy scores at baseline. The Apathetic group's depression scores did not meet criteria for clinically significant depression, however. At baseline, the Apathetic group had worse DRS scores than the Non-apathetic group at baseline. At follow-up18 months later, the Apathetic group continued to perform significantly worse on the DRS than the Non-apathetic group. Further, there was a group x time interaction, with the Apathetic group declining more steeply for nearly all cognitive variables (DRS, free recall, Symbol Digit modalities, Stroop reading and interference, letter/number sequencing, phonemic and semantic fluency). The only measures that did not differentially decline were Digits forwards and backwards and alternating fluency. Authors report that eight individuals converted to dementia from the Apathetic group, whereas only one converted to dementia from the Non-apathetic group. This difference in frequency of conversion to dementia was significant.

Authors conclude that apathy may be a predictor for cognitive decline and dementia. They suggest that apathy and cognitive decline in PD may be related to loss of cholinergic neurons in the basal forebrain nuclei, although this was not studied directly.

A critique of this study is that the patient groups were not matched at baseline. The Apathetic group had worse DRS scores, depression scores, and motor severity, than the Non-apathetic group. The authors note that depression and motor severity did not correlate with the follow-up DRS score, so they were not used as covariates. Related to the differences in baseline DRS scores, there is no discussion of how baseline differences in apathy and cognitive status can be separated as contributing to cognitive decline and dementia incidence. Importantly, it may be the case that the Apathetic group's poorer cognition at baseline is more predictive of dementia than their apathy status. For this reason stating that "apathy heralds cognitive decline and dementia" seems a strong conclusion given the confound of differences in baseline cognition. Authors note in the discussion section that they cannot rule this possibility out.

A further weakness relates to the classification of "dementia". One of the major findings of the study is that the Apathetic group had a higher percentage of individuals that converted to dementia after an 18 month period. Although the authors mentioned that they used the guidelines from Emre et al. (2007), there was lack of further specification. For example, these guidelines include an assessment on how cognitive status affects daily functioning (in other words activities of daily living). This was not assessed in the present study. Dementia definition in a disorder like PD that already involves multiple cognitive deficits is controversial. It would have been helpful to know exactly what criteria authors were using to define the conversion to dementia.

In conclusion, this study raises important questions. For the future, it would be important to know how the trajectory of apathy affects cognition and vice versa. For example, does apathy lead to cognitive decline only after reaching clinical significance? Is the rate of decline in parallel, or is one faster than the other? These types of questions can be answered with longitudinal designs that examine the trajectories of change over multiple time points. While the current study confirms that apathy and cognitive dysfunction are clearly linked, it will be future studies using more sophisticated trajectory designs, as well matched groups at baseline, that will help elucidate whether apathy predicts cognitive decline and conversion to dementia.

Lindsey Kirsch-DarrowAbout Lindsey Kirsch-Darrow, MS
Lindsey Kirsch-Darrow, MS, was born in Atlanta, Georgia, and received her B.S. in Neuroscience from Furman University. Currently, she is a doctoral candidate in Clinical & Health Psychology at the University of Florida, where she is specializing in neuropsychology. Her dissertation was funded by a National Institutes of Health National Research Service Award, and is under the mentorship of Dr. Dawn Bowers. It involves Parkinson's disease, cognitive functioning, depression, and apathy. Lindsey is currently completing a clinical neuropsychology internship at the University of Alabama/Veterans Affairs Medical Center Consortium Site in Birmingham, AL. She intends to pursue a clinical academic career upon completion of a post-doctoral work.

Dawn BowersAbout Dawn Bowers, PhD
Dawn Bowers, PhD, is a Professor in the Department of Clinical and Health Psychology at the University of Florida. She is Director of the Cognitive Neuroscience Laboratory at the McKnight Brain Institute, area head of the Neuropsychology Division (http://neuropsy.phhp.ufl.edu), and a UF Research Foundation Professor. Dr. Bowers received her PhD from the University of Florida, interned at the Boston Veterans Administration Hospital, and completed a post-doctoral fellowship in behavioral neurology. Her research has spanned laterality, attention, and the neuropsychology of emotion using diverse experimental approaches, from psychophysiology to face digitizing. She has over 150 research publications, 200 peer-reviewed research presentations, and one book.