Sex differences in Parkinson disease-associated episodic memory and processing speed deficits.

OBJECTIVES: This study aims to address a gap in the data on cognitive sex differences in persons living with Parkinson disease (PD). There is some evidence that cognitive dysfunction is more severe in male PD, however data on episodic memory and processing speed is incomplete. METHODS: One hundred and sixty-seven individuals with a diagnosis of PD were included in this study. Fifty-six of those individuals identified as female. The California Verbal Learning Test 1st edition and the Wechsler Memory Scale 3rd edition were used to evaluate verbal and visuospatial episodic memory and the Wechsler Adult Intelligence Scale 3rd edition was used to evaluate processing speed. Multivariate analysis of covariance was used to identify sex-specific differences across groups. RESULTS: Our results show that males with PD performed significantly worse than females in verbal and visuospatial recall as well as a trend for the processing speed task of coding. CONCLUSIONS: Our finding of superior performance among females with PD in verbal episodic memory is consistent with reports in both healthy and PD individuals; however, females outperforming males in measures of visuospatial episodic memory is unique to PD. Cognitive deficits preferentially affecting males appear to be associated with frontal lobe-related function. Therefore, males may represent a disease subgroup more susceptible to disease mechanisms affecting frontal lobe deterioration and cognitive disturbances in PD.

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease.

OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. RESULTS: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. CONCLUSIONS: These data do not justify use of CoQ as a treatment to slow functional decline in HD. CLINICALTRIALSGOV IDENTIFIER: NCT00608881. CLASSIFICATION OF EVIDENCE: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.

Subjective Cognitive Complaints in Parkinson Disease Without Dementia: A Preliminary Study.

Little is known about the subjective cognitive complaints of individuals with Parkinson disease (PD). Such complaints have become a topic of interest recently as they play a role in the diagnosis of neurocognitive disorders. The aim of this preliminary study was to determine whether a sample of nondemented individuals with PD reported significantly more difficulties with multiple elements of cognition than a control sample and to assess the relation between their ratings and demographics, motor symptom severity, neuropsychological test performance, and measures of depression and anxiety. Forty nondemented individuals with PD and 27 healthy individuals completed a questionnaire assessing everyday cognitive difficulties. Independent t tests indicated that individuals with PD reported significantly more cognitive complaints in general and in specific tasks involving complex attention, executive function, processing speed, and verbal fluency but not memory. Questionnaire ratings significantly correlated with measures assessing anxiety, verbal memory, processing speed, and verbal fluency. Results suggest that it is important to ask individuals with PD about cognitive complaints across several cognitive domains and also inquire about symptoms of anxiety, which may be related to their self-reported cognitive difficulties.

Predictors of HVOT performance in Parkinson's disease.

Evidence suggests that the Hooper Visual Organization Test (HVOT) has naming and executive components that vary in size depending on neurological diagnosis. The current study used a sample of individuals with Parkinson's disease (PD) to demonstrate for the first time that an executive measure can be the best predictor of HVOT performance. Forty-eight nondemented and nondepressed individuals with idiopathic PD completed the HVOT and other measures of visuoperception, executive function, and visual confrontation naming. Despite average performance on all neuropsychological measures, an executive measure, time to complete Trail-Making Test Part B minus time to complete Part A, was clearly the best predictor of HVOT performance in a standard regression. The pattern of neurocognitive predictors is unlike that reported in healthy individuals and other patient samples. This finding suggests that the presence of a neuropathological process can alter neurocognitive correlates even when performance is intact, and supports the contention that executive function is paramount in the cognitive profile associated with PD.

The clinical significance of neuropsychological changes following bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease.

Despite the clinical importance of the question, a number of methodological issues have limited firm conclusions regarding the cognitive safety of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD). Amongst these issues, studies have generally failed to consider the postoperative changes that occur within individual patients. This study utilized reliable change indices (RCIs) derived from a PD sample to determine the frequency of clinically significant postoperative decline on a battery of neuropsychological measures. This approach addresses measurement reliability, potential practice effects, and disease progression. The proportion of patients experiencing clinically significant postoperative decline on measures of list learning and verbal fluency was greater than expected based on disease progression; however, the majority of patients (55%) did not experience a significant decline in performance on any of the cognitive tests administered, and only one experienced decline on more than one test. Therefore, the statistically significant declines on measures of list learning and verbal fluency observed in the sample as a whole were the result of clinically significant declines experienced by a minority of participants.

Cognitive deficits in essential tremor consistent with frontosubcortical dysfunction.

Essential tremor (ET) is increasingly thought to involve a heterogeneous group of patients, with some also exhibiting symptoms of Parkinson's disease (PD), including cognitive deficits. The goal of this study was to utilize a broad battery of neuropsychological measures to compare the cognitive function of 33 ET patients with that of 33 matched PD patients and 21 normal controls. Results indicated that the ET group performed significantly worse than controls across multiple cognitive domains, but performed remarkably similar to PD patients, consistent with frontosubcortical dysfunction.

Dopamine dependency of cognitive switching and response repetition effects in Parkinson's patients.

A group of people with Parkinson's disease and a group of matched controls were tested on a task involving a switch between perceptual dimensions. Patients were tested both 'on' and 'off' their normal medication cycles. Stimuli appeared in pairs for each trial, with each stimulus consisting of a color and a shape. One dimension of color and one of shape were mapped to each of two response keys. A cue was presented concurrently with each stimulus to indicate whether to respond on the basis of color or shape, following procedures developed by Hayes et al. [Hayes, A.E., Davidson, M.C., Keele, S.W., and Rafal, R.D. (1998). Toward a functional analysis of the basal ganglia. Journal of Cognitive Neuroscience, 10, 178-198]. Replicating previous literature, abnormally large switch costs were observed in patients who were off their normal medication cycles. A novel finding was that patients in the 'on' state demonstrated a slight reversal of switch costs. Also novel, reaction time (RT) costs associated with switching between response keys, and interactions between response switching and task switching were influenced predominantly by on-off dopamine manipulations. It is concluded that abnormal task switching costs and response repetition effects likely reflect impairments of activation and inhibition, and both effects are dopamine-dependent.

Recognition memory in Parkinson's disease with and without dementia: evidence inconsistent with the retrieval deficit hypothesis.

Parkinson's disease (PD) has been associated with a pattern of performance on memory tests in which free recall is impaired but recognition and cued recall are intact, indicating problems with memory retrieval. Recent findings suggest that PD patients exhibit deficits in recognition as well as free recall, however. The current study set out to provide clear evidence that recognition and cued recall are not intact in PD. Ninety-nine idiopathic PD patients were administered the California Verbal Learning Test and their performance was compared to a well-matched normative sample. A profile analysis revealed that nondemented patients exhibited deficits on measures of cued recall and delayed recognition that were similar in magnitude to that of free recall. This was also the case for the cued recall deficits exhibited by demented patients; however, in this group recognition was worse than free recall. In both groups poor recognition appeared due to an elevated number of false positive errors. These results are inconsistent with the retrieval deficit hypothesis but support the notion that PD memory problems are secondary to prefrontal dysfunction.

Temporal evolution of oscillations and synchrony in GPi/muscle pairs in Parkinson's disease.

Both standard spectral analysis and time-dependent phase correlation techniques were applied to 27 pairs of tremor-related single units in the globus pallidus internus (GPi) and EMG of patients with Parkinson's disease (PD) undergoing stereotactic neurosurgery. Over long time-scales (approximately 60 s), GPi tremor-related units were statistically coherent with restricted regions of the peripheral musculature displaying tremor. The distribution of pooled coherence across all pairs supports a classification of GPi cell/EMG oscillatory pairs into coherent or noncoherent. Analysis using approximately 2-s sliding windows shows that oscillatory activity in both GPi tremor units and muscles occurs intermittently over time. For brain/muscle pairs that are coherent, there is partial overlap in the times of oscillatory activity but, in most cases, no significant correlation between the times of oscillatory subepisodes in the two signals. Phase locking between coherent pairs occurs transiently; however, the phase delay is similar for different phase-locking subepisodes. Noncoherent pairs also show episodes of transient phase locking, but they occurred less frequently, and no preferred phase delay was seen across subepisodes. Tremor oscillations in pallidum and EMGs are punctuated by phase slips, which were classified as synchronizing or desynchronizing depending on their effect on phase locking. In coherent pairs, the incidence of synchronizing slips is higher than desynchronizing slips, whereas no significant difference was seen for noncoherent pairs. The results of this quantitative characterization of parkinsonian tremor provide a foundation for hypotheses about the structure and dynamical functioning of basal ganglia motor control networks involved in tremor generation.

The relationship between executive function and verbal memory in Parkinson's disease.

A growing body of evidence suggests that the various cognitive symptoms found in Parkinson's disease (PD) are secondary to executive dysfunction. Studies addressing this possibility for memory impairment specifically have not included measures of working memory nor have they ruled-out potential mediating variables such as overall level of cognitive impairment or depression. The purpose of this study was to include measures of these variables in determining the relationship between multiple aspects of executive function and delayed verbal recall in 32 idiopathic PD patients. Results were consistent with the original hypothesis and further suggest that working memory is a key factor in recall memory and may mediate the relationship between other executive measures and recall in PD.