In a 24-week, randomized, double-blind, placebo-controlled, multicenter study of rivastigmine, 487 patients with dementia associated with Parkinson disease underwent assessment of attention on the Cognitive Drug Research computerized cognitive assessment system before dosing and 16 and 24 weeks later. Significant benefits of rivastigmine over placebo were seen on all aspects of attention assessed: sustained attention, focused attention, consistence of responding, and central processing speed.
"A wide variety of tests are used for the assessment of EF in PD, but it is not clear which are most sensitive. The accurate identification of MCI in ndPD patients is critical, as cholinesterase inhibitors have been associated with improved attention  and increased frontal brain activity in cognitively impaired PD . In addition, studies have shown that cognitive dysfunction is a risk factor for the subsequent development of Parkinson's disease dementia , and cognitive impairment in ndPD predicts disability, impaired driving, and increased risk for falls, which results in increased medical care costs . "
[Show abstract][Hide abstract] ABSTRACT: Background: We examined the sensitivity of different executive function measures for detecting deficits in Parkinson’s disease patients without dementia.
Methods: Twenty-one non-demented PD subjects and 21 neurologically healthy controls were administered widely used clinical executive functioning measures as well as the NIH EXAMINER battery, which produces Cognitive Control, Working Memory, and Verbal Fluency scores, along with an overall Executive Composite score, using psychometrically matched scales.
Results: No significant differences between groups were observed on widely used clinical measures. The PD patients scored lower than controls on the EXAMINER Executive Composite, Cognitive Control, and Working Memory Scores.
Conclusions: The NIH EXAMINER Executive Composite and Cognitive Control Scores are sensitive measures of executive dysfunction in non-demented PD, and may be more sensitive than several widely used measures. Results highlight the importance of careful test selection when evaluating for mild cognitive impairment in PD.
"Of note, the cholinergic system is widely distributed in the brain and it is more affected in DLB than in Alzheimer's disease (AD) patients (Kotagal et al. 2012). This concept is amply supported by pharmacological evidences which suggest that (1) anticholinergic drugs can induce a symptom profile of altered arousal comparable to flCog in DLB (Perry et al. 1999) and (2) cholinesterase inhibitors can significantly improve flCog and attentional function in DLB (McKeith et al. 2000; Onofrj et al. 2003; Wesnes et al. 2005). "
[Show abstract][Hide abstract] ABSTRACT: Dementia with Lewy bodies (DLB) is characterized by fluctuation in cognition and attention. Thalamocortical connectivity and integrity of thalami are central to attentional function. We hypothesize that DLB patients with marked and frequent fluctuating cognition (flCog) have a loss of thalamocortical connectivity, an intrinsic disruption to thalamic structure and imbalances in thalamic neurotransmitter levels. To test this, magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and proton MR spectroscopy on thalami were performed on 16 DLB, 16 Alzheimer's disease (AD) and 13 healthy subjects. MRI and DTI were combined to subdivide thalami according to their cortical connectivity and to investigate microstructural changes in connectivity-defined thalamic regions. Compared with controls, lower N-acetyl-aspartate/total creatine (NAA/tCr) and higher total choline/total creatine (tCho/tCr) values were observed within thalami of DLB patients. tCho/tCr increase was found within right thalamus of DLB patients as compared with AD. This increase correlated with severity and frequency of flCog. As compared with controls, DLB patients showed bilateral damage within thalamic regions projecting to prefrontal and parieto-occipital cortices, whereas AD patients showed bilateral alteration within thalamic region projecting to temporal cortex. We posit that microstructural thalamic damage and cholinergic imbalance may be central to the etiology of flCog in DLB.
"The CDR System has previously been validated in dementia  and traumatic brain injury , and is used in a variety of disease states and cognitive disorders including dementia, epilepsy and sleep disorders, to demonstrate both efficacy and safety of drugs [26-28]. The battery uses alternate forms of tests and randomizes these across repeated assessments. "
[Show abstract][Hide abstract] ABSTRACT: There is need for a cognitive test battery that can be easily used in clinical practice to detect or monitor cognitive performance in patients with multiple sclerosis (MS). In order to conduct, in this patient group, a preliminary investigation of the validity and utility of a brief computerized battery, the Cognitive Drug Research (CDR) battery, we longitudinally assessed cognition in patients with relapsing remitting (RR) MS.
Forty-three mildly disabled, clinically active RRMS patients were repeatedly assessed with the Digit Symbol Substitution Test (DSST), Paced Auditory Serial Addition Test (PASAT) and five composite scores derived from the CDR computerized cognitive test system (CDR System): Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory and Speed of Memory. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) measured disability.
The composite scores from the CDR battery generally showed excellent test-retest reliability over the repeated assessments, though was low on occasions for the Quality of Working Memory and Quality of Episodic Memory measures. The CDR measures tended to be highly correlated with other measures of cognition (DSST and PASAT) and were also strongly related to disability (EDSS and MSFC). Baseline scores indicated large impairments to visual information processing speed and attention (DSST, Cohen's d 1.1; Power of Attention d 1.4 [reaction time on tasks of focussed and sustained attention]), and a moderate impairment both to sustained attention (Continuity of Attention d 0.6) and complex information processing speed (Speed of memory d 0.7 [reaction time on tasks of working and episodic Memory]), when compared to normative data derived from healthy volunteers enrolled in a series of separate, prior clinical trials. Working memory (Quality of Working Memory) and episodic memory (Quality of Episodic Memory) were unimpaired.
Preliminary validation of the CDR System indicated that for most, but not all measures psychometric properties were adequate and the measures were related to disability (EDSS and MSFC) and other measures of cognition.
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