Cognitive Rehabilitation.

PURPOSE OF REVIEW: This article provides a definition of and introduction to cognitive rehabilitation. It discusses different approaches to cognitive rehabilitation (ie, restorative, compensatory, and metacognitive). It also reviews types of memory impairment and how they can be distinguished to improve treatment design and implementation. RECENT FINDINGS: Neural plasticity as a biological substrate for functional changes from cognitive rehabilitation is an exciting new area of research. SUMMARY: This article provides a high-level review of cognitive rehabilitation and presents a complex case example.

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.

Dimensions of apathy in Parkinson's disease: exploratory factor analysis of the apathy scale.

Apathy, an intrinsic disorder of motivation, can manifest in cognitive, affective, and behavioral domains. Recent attempts to formalize diagnostic criteria for apathy have advocated this triadic structure. The Apathy Scale (AS) is the only recommended measure for assessing apathy in Parkinson's disease (PD) by a Movement Disorders task force. We tested the hypothesis that the AS distinctly measures the three proposed domains of apathy in PD. Participants were 226 non-demented PD patients. Apathy Scale data were examined with exploratory factor analysis (EFA). The three factor solution resembled the triadic structure of cognitive, behavioral, and affective domains; however, adjustments to the AS may be appropriate.

Apathy and depression: separate factors in Parkinson's disease.

The objective of this study was to test the hypothesis that apathy and depression are dissociable in Parkinson disease (PD) by conducting a confirmatory factor analysis (CFA) of items from two commonly used mood scales. A total of 161 non-demented PD patients (age = 64.1; ± 8.4 years) were administered the Apathy Scale and the Beck Depression Inventory-II. Items were hypothesized to load onto four factors: (1) an apathy factor representing loss of motivation, (2) dysphoric mood factor representing sadness and negativity, (3) loss of interest/pleasure factor representing the features common to both apathy and depression, and (4) a somatic factor representing bodily complaints. Results indicated a good fit for the overall CFA model, χ² (128, N = 146) = 194.9; p<.01. RMSEA was .060 (p = .16). The four-factor model was significantly better than all alternative nested models at p < .001, including an overarching single factor model, representing "depression." Results support the concept that apathy and depression are discrete constructs. We suggest a "factor based" scoring of the Apathy Scale and Beck Depression Inventory-II that disentangles symptoms related to apathy, depression, overlapping symptoms, and somatic complaints. Such scoring may be important in providing useful information regarding differential treatment options.

Greater improvement in quality of life following unilateral deep brain stimulation surgery in the globus pallidus as compared to the subthalamic nucleus.

While deep brain stimulation (DBS) surgery is a well-accepted treatment for Parkinson disease (PD) that improves overall quality of life (QoL), its effects across different domains of QoL are unclear. The study reported here directly compared the effects of unilateral DBS in subthalamic nucleus (STN) or globus pallidus (GPi) on QoL in 42 non-demented patients with medication-refractory PD. Patients were enrolled in the COMPARE trial, a randomized clinical trial of cognitive and mood effects of STN versus GPi DBS conducted at the University of Florida Movement Disorders Center. Patients underwent motor, mood, verbal fluency and QoL (Parkinson disease questionnaire: PDQ-39) measures before and 6 months following surgery. Groups experienced motor and mood improvements that did not differ by target. Patients with STN DBS evidenced a slight decrement on letter fluency. On average, all patients endorsed better overall QoL after surgery. However, despite similar motor and mood improvements, GPi patients improved more than STN patients (38 vs. 14%, respectively; P = 0.03). Patients reported better QoL on subscales of mobility, activities of daily living (ADLs), emotional well-being, stigma, cognition and discomfort, but not on those of social support and communication. Improvements on the mobility, ADLs, stigma and social support subscales were greater amongst GPi patients. In regression analyses, only depression changes independently predicted changes in overall QoL as well as emotional well-being and social support changes. Within the STN group only, declining category fluency scores correlated with poorer QoL on the communication subscale. Unilateral DBS in both STN and GPi improved QoL overall and in disparate domains 6 months after surgery. Patients receiving GPi DBS reported greater improvements that cannot be explained by differential mood or motor effects; however, verbal fluency changes may have partially contributed to lesser QoL improvements amongst STN patients.

Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial.

OBJECTIVE: 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. METHODS: Fifty-two subjects were randomized to unilateral STN or GPi DBS. The co-primary outcome measures were the Visual Analog Mood Scale, and verbal fluency (semantic and letter) at 7 months post-DBS in the optimal setting compared to pre-DBS. At 7 months post-DBS, subjects were tested in four randomized/counterbalanced conditions (optimal, ventral, dorsal, and off DBS). RESULTS: Forty-five subjects (23 GPi, 22 STN) completed the protocol. The study revealed no difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes pre- to post-DBS in the optimal setting (Hotelling's T(2) test: p = 0.16 and 0.08 respectively). Subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally. Comparison of the other 3 DBS conditions to pre-DBS showed a larger deterioration of letter verbal fluency in STN, especially when off DBS. There was no difference in UPDRS motor improvement between targets. INTERPRETATION: There were no significant differences in the co-primary outcome measures (mood and cognition) between STN and GPi in the optimal DBS state. Adverse mood effects occurred ventrally in both targets. A worsening of letter verbal fluency was seen in STN. The persistence of deterioration in verbal fluency in the off STN DBS state was suggestive of a surgical rather than a stimulation-induced effect. Similar motor improvement were observed with both STN and GPi DBS.

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 Parkinson's 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 > or =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.

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.

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 Parkinson's 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.

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 Parkinson's 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. > or = 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 Parkinson's 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 deep brain stimulation induce apathy in Parkinson's disease?

Chronic deep brain stimulation (DBS) is an important therapeutic advancement for the treatment of motor symptoms in Parkinson's disease (PD). However, its effects on non-motor symptoms are not well understood. Several studies have reported motivational disturbances and apathy after DBS surgery. Recent studies are beginning to more carefully examine the relationship between DBS and apathy. This review summarizes and evaluates the current state of the literature on apathy after DBS surgery, discusses methodological limitations in the literature, and makes suggestions for future research.

Limbic, associative, and motor territories within the targets for deep brain stimulation: potential clinical implications.

The use of deep brain stimulation (DBS) has recently been expanding for the treatment of many neurologic disorders such as Parkinson disease, dystonia, essential tremor, Tourette's syndrome, cluster headache, epilepsy, depression, and obsessive compulsive disorder. The target structures for DBS include specific segregated territories within limbic, associative, or motor regions of very small subnuclei. In this review, we summarize current clinical techniques for DBS, the cognitive/mood/motor outcomes, and the relevant neuroanatomy with respect to functional territories within specific brain targets. Future development of new techniques and technology that may include a more direct visualization of "motor" territories within target structures may prove useful for avoiding side effects that may result from stimulation of associative and limbic regions. Alternatively, newer procedures may choose and specifically target non-motor territories for chronic electrical stimulation.

Deep brain stimulation and the role of the neuropsychologist.

Deep brain stimulation (DBS) now plays an important role in the treatment of Parkinson's disease, tremor, and dystonia. DBS may also have a role in the treatment of other disorders such as obsessive-compulsive disorder, Tourette's 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.

Startling facts about emotion in Parkinson's disease: blunted reactivity to aversive stimuli.

The amygdala is closely linked to basal ganglia circuitry and plays a key role in danger detection and fear-potentiated startle. Based on recent findings of amygdalar abnormalities in Parkinson's disease, we hypothesized that non-demented patients with this illness would show blunted reactivity during aversive/unpleasant events, as indexed by diminished emotional modulation of the startle eyeblink response. To test this hypothesis, 23 idiopathic patients with Parkinson's disease and 17 controls viewed standardized sets of aversive, pleasant and neutral pictures for 6 s each. During this time, white noise bursts (50 ms, 95 db) were binaurally presented to elicit startle eyeblink responses, measured from electrodes over the orbicularis oculi. After viewing each picture, subjects provided ratings of valence and arousal. The Parkinson's disease patients were in the early to middle stages of their disease, not demented or depressed, and were tested 'on' dopaminergic medication. The two groups were similar in age, education, gender and cognitive screening status. The control group had larger startle responses when viewing negative, aversive pictures than neutral or pleasant pictures. As predicted, startle enhancement during aversive pictures was significantly muted in the Parkinson's disease patients. This blunting was not due to abnormalities in the mechanics of the startle eyeblink per se. Nor was it related to depression symptoms, medications (psychotropics), or failure to perceive/appreciate the negative meaning of aversive pictures (i.e. normal valence ratings). Reduced startle reactivity in the disease group was related to disease severity (Hoehn-Yahr) and occurred in the context of reduced arousal ratings of aversive pictures. These findings of blunted startle reactivity add to the literature on emotional changes associated with Parkinson's disease. The basis for this muted reactivity is unknown but may involve an amygdala-based translational defect whereby the results of cognitive appraisal are not appropriately transcoded into somato-motor-arousal responses normally associated with an aversive motivational state. This may arise from faulty dopaminergic gating of the amygdala, resulting in 'inhibition' of the amygdala in the manner described by Marowsky et al. (Marowsky A, Yanagawa Y, Obata K, Vogt E. Neuron 2005; 48: 1025-37). More broadly, the findings of muted reactivity to aversive stimuli may reflect a 'bradylimbic' affective disturbance in patients with Parkinson's disease. Future studies are needed to address whether the physiologic blunting observed here might be a useful correlate of apathy.