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ObjectivesHuntington disease (HD) is associated with a variety of cognitive deficits, with prominent difficulties in working memory (WM). WM deficits are notably compromised in early-onset and prodromal HD patients. This study aimed to determine the feasibility of a computerized WM training program (Cogmed QM), novel to the HD population.MethodsNine patients, aged 26–62, with early stage HD underwent a 25-session (5 days/week for 5 weeks) WM training program (Cogmed QM). Training exercises involved the manipulation and storage of verbal and visuospatial information, with difficulty adapted as a function of individual performance. Neuropsychological testing was conducted before and after training, and performance on criterion WM measures (Digit Span and Spatial Span), near-transfer WM measures (Symbol Span and Auditory WM), and control measures were evaluated. Post-training interviews about patient experience were thematically analyzed using NVivo software.ResultsSeven of nine patients demonstrated adherence to the training and completed all sessions within the recommended timeframe of 5 weeks. All adherent patients showed improvement on the Cogmed tasks as defined by the Improvement Index (M = 22.17, SD = 8.84, range = 13–36). All adherent patients reported that they found training helpful (n = 7), and almost all felt that their memory improved (n = 6). Participants also expressed that the training was difficult, sometimes frustrating, and time consuming.ConclusionsThis pilot study provides support for feasibility of computerized WM training in early-stage patients with HD. Results suggest that HD patients perceive benefits of intensive WM training, though a full-scale and controlled intervention project is needed to understand the size of the effect and reliability of changes over time.Trial registrationClinicalTrials.gov, Registry number NCT02926820

Parkinson disease (PD) is the most common movement disorder, characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. While the cause of this disease is largely unknown, a rare autosomal dominant familial form of PD is caused by a genetic mutation in the leucine-rich repeat kinase 2 (LRRK2) gene that presumably leads to a gain-of-function of LRRK2 kinase activity. Here, we explored the potential of over expression of this human gene in a new transgenic rat model to serve as an animal model for PD. Commercially available BAC transgenic rats expressing human LRRK2 with the familial PD mutation, R1441G, and their wild-type siblings were tested for deficits in motor function, sensorimotor gating, and higher cognitive function reminiscent of PD through the ages of 3, 6, 9 and 12 months. At 12 months of age, rats were exposed to intraperitoneal injections of the environmental toxin Paraquat or saline. Our results indicate that LRRK2R1441G transgenic rats do not show signs of neurodegeneration and do not develop significant motor or cognitive deficits until the age of 16 months. In addition, LRRK2R1441G transgenic rats did not show increased vulnerability to sub-toxic doses of Paraquat. Gene expression studies indicate that despite genomic presence and initial expression of the transgene, its expression was greatly reduced in our aged rats. We conclude that the transgenic LRRK2R1441G rat is not a valid model for studying the pathology of PD and discuss this in relation to other transgenic rat models.

This novel questionnaire can be used in both clinical and research settings to better understand the impact of memory changes on the day-to-day functioning of older adults and to monitor outcomes of support programs for this population.