Lindsey Kirsch-Darrow

Cognition and Mood in Parkinson's Disease in Subthalamic Nucleus versus Globus Pallidus Interna Deep Brain Stimulation: The COMPARE Trial

Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease.

Dissociating apathy and depression in Parkinson disease

Objective: To examine the hypothesis that apathy is a core feature of Parkinson disease (PD) and that apathy can be dissociated from depression. Methods: Eighty patients with PD and 20 patients with dystonia completed depression and apathy measures including the Marin Apathy Evaluation Scale (AES), Beck Depression Inventory (BDI), and Centers for Epidemiologic Studies–Depression Scale (CES-D). Results: There was a significantly higher severity and frequency of apathy in PD (frequency = 51%, 41/80) than in dystonia (frequency = 20%, 4/20). Apathy in the absence of depression was frequent in PD and did not occur in dystonia (PD = 28.8%, dystonia = 0%). Conclusions: Patients with Parkinson disease (PD) experienced significantly higher frequency and severity of apathy when compared with patients with dystonia. Apathy may be a “core” feature of PD and occurs in the absence of depression.

COGNITIVE DECLINES ONE YEAR AFTER UNILATERAL DEEP BRAIN STIMULATION SURGERY IN PARKINSON’S DISEASE: A CONTROLLED STUDY USING RELIABLE CHANGE

Conflicting research suggests that deep brain stimulation surgery, an effective treatment for medication-refractory Parkinsons disease (PD), may lead to selective cognitive declines. We compared cognitive performance of 22 PD patients who underwent unilateral DBS to the GPi or STN to that of 19 PD controls at baseline and 12 months. We hypothesized that compared to PD controls, DBS patients would decline on tasks involving dorsolateral prefrontal cortex circuitry (letter fluency, semantic fluency, and Digit Span Backward) but not on other tasks (Vocabulary, Boston Naming Test), and that a greater proportion of DBS patients would fall below Reliable Change Indexes (RCIs). Compared to controls, DBS patients declined only on the fluency tasks. Analyses classified 50% of DBS patients as decliners, compared to 11% of controls. Decliners experienced less motor improvement than non-decliners. The present study adds to the literature through its hypothesis-driven method of task selection, inclusion of a disease control group, longer-term follow-up and use of Reliable Change. Our findings provide evidence that unilateral DBS surgery is associated with verbal fluency declines and indicate that while these changes may not be systematically related to age, cognitive or depression status at baseline, semantic fluency declines may be more common after left-sided surgery. Finally, use of Reliable Change highlights the impact of individual variability and indicates that fluency declines likely reflect significant changes in a subset of patients who demonstrate a poorer surgical outcome overall.

The trajectory of apathy after deep brain stimulation: from pre-surgery to 6 months post-surgery in Parkinson's disease.

Deep brain stimulation (DBS) has been associated with increased apathy in patients with PD, yet studies lack longitudinal data and have not assessed differences between sites of implantation (i.e. STN versus GPi). We assessed apathy prior to surgery and 6 months post-surgery using a longitudinal design-latent growth curve modeling. We hypothesized that apathy would increase post-surgery, and be related to subthalamic nucleus (versus globus pallidus interna) implantation. Forty-eight PD patients underwent unilateral surgery to either GPi or STN and completed the Apathy Scale prior to surgery and 2, 4, and 6 months post-surgery. Forty-eight matched PD controls completed the Apathy Scale at a 6-month interval. Results indicated apathy increased linearly from pre- to 6-months post-DBS by .66 points bi-monthly, while apathy in the control group did not change. There was no relationship between apathy and DBS site. Higher baseline depression was associated with higher baseline apathy, but not with change in apathy. Middle-aged adults (<65) had a steeper trajectory of apathy than older adults (≥ 65). Apathy trajectory was not related to motor severity, laterality of DBS, levodopa medication reduction, or motor changes after surgery.

Deep Brain Stimulation and the Role of the Neuropsychologist

Deep brain stimulation (DBS) now plays an important role in the treatment of Parkinsons disease, tremor, and dystonia. DBS may also have a role in the treatment of other disorders such as obsessive-compulsive disorder, Tourettes syndrome, and depression. The neuropsychologist plays a crucial role in patient selection, follow-up, and management of intra-operative and post-operative effects (Pillon, 2002; Saint-Cyr & Trepanier, 2000). There is now emerging evidence that DBS can induce mood, cognitive, and behavioral changes. These changes can have dramatic effects on patient outcome. There have been methodological problems with many of the studies of DBS on mood, cognition, and behavior. The neuropsychologist needs to be aware of these issues when following up patients, and constructing future studies. Additionally, this article will review all aspects of the DBS procedure that can result in mood, cognitive, and behavioral effects and what role(s) the neuropsychologist should play in screening and follow-up.

Examination of the Lille Apathy Rating Scale in Parkinson Disease

Apathy is a unique, multidimensional syndrome commonly encountered in patients with Parkinson disease (PD). Recently, the Lille Apathy Rating Scale (LARS), a semistructured interview yielding a global score, and composite subscores for different domains of apathy (i.e., cognitive, behavioral, affective, self awareness), was developed and given to a sample of patients with PD in France. This study is the first outside of its original developers to examine the English language version of the LARS in PD. We found the LARS to be a coherent instrument demonstrating both convergent and divergent validity, as compared to the Apathy Scale (AS) and Beck Depression Inventory (BDI‐II). Using a receiver operating characteristic (ROC) analysis comparing the LARS to the AS, a validated and widely‐used measure, we identified a cut‐off score (sensitivity = 64%, specificity = 92%, PPV = 88%, NPV = 75%) that was higher than that proposed by the original authors, who derived their cut‐off by comparing LARS global scores to clinical judgments of apathy. Although the present study does not compare the LARS to a diagnostic gold standard or promote its utility for diagnosing apathy, it provides further support for the LARS as a promising instrument to examine apathy in PD.

Inappropriate crying and laughing in Parkinson disease and movement disorders

Objective. To examine in a pilot study inappropriate crying and laughing (also termed pseudobulbar affect (PBA)) and underlying mood disturbances in a large clinic based population of Parkinsons disease and movement disorder patients. Background. PBA is characterized by uncontrollable laughter without mirth, or alternatively crying without the feeling of sadness. It is a common condition affecting more than one million people with neurological diseases. While PBA has been studied in many neurological diseases, little is known about its prevalence in movement disorders, or its relationship to more chronic mood disturbances. We carried out this pilot study to examine this relationship. Methods. Seven hundred and nineteen out of 860 consecutive patients who visited our Movement Disorders Center met inclusion criteria (i.e. ≥18 years of age, formal diagnosis by a movement disorder specialist, completion of PBA questionnaire, and absence of brain surgery including deep brain stimulation). All subjects were interviewed for symptoms of PBA during their visit. In addition, 661 of these patients completed both the Visual Analog Mood Scale (VAMS) and Beck Depression Inventory I (BDI-I). Results. Thirty-seven of the 719 reported PBA symptoms; 75.7% (28/37) had pathological ‘crying’, 13.5% (5/37) had pathological ‘laughing’ and 10.8% (4/37) had both. The prevalence of PBA in individual diagnostic categories was: 4.7% (18/387) of idiopathic Parkinsons disease (PD), 2.7% (2/74) of primary dystonia, 3.1% (2/65) of essential tremor (ET), 7.8% (8/108) of patients with other forms of Parkinsonism, 21.7% (5/23) of psychogenic movement disorders, 0% (0/18) of patients with combined PD and ET, and 4.5% (2/44) of other movement disorders. Patients with PBA had a higher total BDI score (P =0.0278) and VAMS ‘tiredness’ score (P=0.0109). In patients on antidepressant therapy the prevalence of PBA was 7.1% compared to 2.7% in the group not on therapy (P=0.0094). Conclusion. PBA was present in most movement disorders, but especially prevalent in parkinsonism. PBA patients in this cohort had more chronic depressive symptoms and tiredness.

Does laterality of motor impairment tell us something about cognition in Parkinson disease

This cross-sectional study investigates the relationship between severity of right- and left-sided motor symptoms and deficits in global cognitive function as well as individual cognitive domains in 117 Parkinson disease patients. Items of the Unified Parkinson Disease Rating Scale Part III were divided into right- and left-sided total scores. Composite scores in verbal fluency, verbal memory, executive function, and visuoperceptual skills were obtained from a full neuropsychological battery. We observed a significant association between right-sided motor impairment and verbal memory, visuoperceptual skills, and verbal fluency, but not executive function. The relationship between right symptoms and verbal fluency was fully mediated by cognitive status, while the relationship between right symptoms and verbal memory as well as visuoperceptual skills was not. Left-sided motor symptoms were not significantly related to any composite cognitive domain. When patients were divided into groups based on the side of predominant symptoms, no group differences were found in performance on the specific cognitive domains. This suggests that the degree of right-sided symptoms is more correlated to specific cognitive domains than is group classification of laterality.

How Cautious Should We Be When Assessing Apathy with the Unified Parkinson's Disease Rating Scale?

Current practice often assesses apathy with a single item from the Unified Parkinsons Disease Rating Scale (UPDRS, item 4). Yet, the relationship between the UPDRS item 4 and the validated Apathy Scale (AS) is unknown. The purpose of this study was to evaluate the operating characteristics of UPDRS item 4 in relation to the AS. Three hundred and one patients with PD were administered the AS and the UPDRS. We compared the UPDRS item 4 to the standard AS classification of ≥14 as apathetic. A receiver operating characteristics (ROC) curve was obtained, and sensitivity, specificity, positive, and negative predictive power were calculated. The ROC curve showed area under the curve as 0.75. A cut‐off of 1 had good sensitivity (81%) but poor specificity (53%; high false positive rate). A cut‐off point of 2 had acceptable specificity (87%) but poor sensitivity (52%, high false negative rate). Continuing to increasing the cut‐off point (e.g., 3, 4) continues to increase specificity at the expense of dramatically reducing sensitivity. These findings suggest the use of caution when screening for apathy with item 4 due to its poor sensitivity in relation to the AS.

Impaired emotion processing from vocal and facial cues in frontotemporal dementia compared to right hemisphere stroke

To advance our understanding about the emotional and cognitive deficits of patients with frontotemporal dementia with behavioral variant (bvFTD), the current study examined comprehension and expression of emotions from prosodic and facial cues in a 66-year-old woman. The patient diagnosed with bvFTD is compared to six patients with acute right hemisphere stroke. Recognition of emotion from prosodic cues was assessed using an identification task in four conditions with decreasing verbal demands (neutral sentences, language-like pseudo sentences, monosyllables, and asyllabic vowel sounds). Repetition of utterances with emotional connotations and self-generated conversations were analyzed to measure relative changes in mean fundamental frequency (f0), f0 variance, speech rate, and intensity along with the facial musculature pattern. The patient showed a marked deficit in identifying emotions in all four prosody conditions; and she did not show much variation in modulating mean f0, f0 variance, speech rate and intensity for all emotion categories when compared to neutral utterances. In addition, this patient demonstrated little to no facial expressions during emotionally provoking tasks, but demonstrated no difficulty recognizing emotions from facial expressions or verbal scenarios. Results show that the patient seems to have selective impairment in recognition of emotions from prosody and expression of emotions using both prosodic and facial features. Impaired processing of emotional prosody and facial expressions could be important for detecting bvFTD with greater right hemisphere atrophy.