Evaluating Recall and Recognition Memory Using the Montreal Cognitive Assessment: Applicability for Alzheimer's and Huntington's Diseases.

We sought to investigate whether the Montreal Cognitive Assessment (MoCA) could provide a brief assessment of recall and recognition using Huntington disease (HD) and Alzheimer disease (AD) as disorders characterized by different memory deficits. This study included 80 participants with HD, 64 participants with AD, and 183 community-dwelling control participants. Random-effects hierarchical logistic regressions were performed to assess the relative performance of the normal control (NC), participants with HD, and participants with AD on verbal free recall, cued recall, and multiple-choice recognition on the MoCA. The NC participants performed significantly better than participants with AD at all the 3 levels of assessment. No difference existed between participants with HD and NC for cued recall, but NC participants performed significantly better than participants with HD on free recall and recognition. The participants with HD performed significantly better than participants with AD at all the 3 levels of assessment. The MoCA appears to be a valuable, brief cognitive assessment capable of identifying specific memory deficits consistent with known differences in memory profiles.

Benton Judgment of Line Orientation (JoLO) Test: A Brief and Useful Measure for Assessing Visuospatial Abilities in Manifest, but not Premanifest, Huntington's Disease.

BACKGROUND: Visuospatial deficits have been described in Huntington's disease (HD); however, the extent of these deficits remains unclear. The Benton Judgment of Line Orientation (JoLO) Test, commonly used to assess visuospatial ability, requires minimal motor involvement. It has demonstrated sensitivity to visuospatial deficits in Parkinson's disease; however, few studies have examined performance on this test in HD. OBJECTIVE: The objective of the current study was to assess visuospatial ability in premanifest and manifest HD using the JoLO. METHODS: A global cognitive measure, the Mattis Dementia Rating Scale (DRS), was used to stratify manifest HD patients as mild (DRS ≥129) vs. moderate-severe (DRS ≤128). Fifty mild, 42 moderate-severe, and 30 premanifest HD subjects, as well as 35 matched controls, were administered the JoLO. HD Burden of Pathology (BOP) scores were used as a measure of disease severity. RESULTS: Results revealed that the total manifest HD sample (p <  0.001), in addition to the mild (p = 0.028), and moderate-severe (p <  0.001), but not premanifest, HD subjects scored significantly lower on the JoLO compared to normal controls. CONCLUSIONS: Our results suggest that the JoLO is useful for detecting visuospatial deficits across various stages of manifest HD. However, any visuospatial impairment that might be present during the premanifest stage of HD was not detected using the JoLO in the present sample.

The Visual Spatial Learning Test: differential impairment during the premanifest and manifest stages of Huntington's disease.

Visual spatial memory was assessed using the Visual Spatial Learning Test (VSLT) in individuals with mild to moderate Huntington's disease (HD), pre-manifest gene carriers for HD, and demographically similar controls. The VSLT has been demonstrated to be a valid, normed measure of non-verbal memory involving minimal motoric responses. The VSLT assesses immediate and delayed memory for designs, positions of the designs, and design/position associations. The HD group was significantly impaired (p < .05) relative to both the control and Pre-HD groups on immediate and delayed memory for the designs, positions, and design/position associations. Although there were no differences between the Pre-HD and control groups on immediate or delayed memory for designs or positions, the Pre-HD group was significantly impaired (p < .05) relative to the control group on immediate and delayed memory for design/position associations. The results offer novel insight into a relatively unexamined memory deficit that may occur in gene carriers for HD prior to phenoconversion. The data indicate that the VSLT may be a useful measure of visuospatial memory during the premanifest and manifest stages of HD.

"Forgetting to remember" in Huntington's disease: a study of laboratory, semi-naturalistic, and self-perceptions of prospective memory.

Prospective memory (PM) is dependent on executive processes known to be impaired in Huntington's disease (HD); however, no study to the authors' knowledge has investigated PM in this group. We examined performance-based, semi-naturalistic, and self-reported PM in 20 individuals diagnosed with mild-moderate HD and 20 demographically similar controls. Relative to controls, HD participants demonstrated significantly lower scores in time-based PM, event-based PM (at a trend level), and the semi-naturalistic PM trial, all of which were marked by omission errors. HD participants demonstrated comparable recognition memory for the PM intentions relative to controls. HD and control participants also showed comparable scores in self-reported PM complaints. The results suggest that HD is associated with deficits in the strategic aspects of PM. HD-associated PM deficits also are evident in real-world situations, which may relate to an apparent meta-memory deficit for PM functioning as indicated by HD participants' overestimation of their PM performance on self-report.

The functional implications of motor, cognitive, psychiatric, and social problem-solving states in Huntington's disease.

OBJECTIVE: Huntington's disease (HD) is a genetic, neurodegenerative disorder characterized by motor, cognitive, and psychiatric dysfunction. In HD, the inability to solve problems successfully affects not only disease coping, but also interpersonal relationships, judgment, and independent living. The aim of the present study was to examine social problem-solving (SPS) in well-characterized HD and at-risk (AR) individuals and to examine its unique and conjoint effects with motor, cognitive, and psychiatric states on functional ratings. METHOD: Sixty-three participants, 31 HD and 32 gene-positive AR, were included in the study. Participants completed the Social Problem-Solving Inventory-Revised: Long (SPSI-R:L), a 52-item, reliable, standardized measure of SPS. Items are aggregated under five scales (Positive, Negative, and Rational Problem-Solving; Impulsivity/Carelessness and Avoidance Styles). Participants also completed the Unified Huntington's Disease Rating Scale functional, behavioral, and cognitive assessments, as well as additional neuropsychological examinations and the Symptom Checklist-90-Revised (SCL-90R). A structural equation model was used to examine the effects of motor, cognitive, psychiatric, and SPS states on functionality. RESULTS: The multifactor structural model fit well descriptively. Cognitive and motor states uniquely and significantly predicted function in HD; however, neither psychiatric nor SPS states did. SPS was, however, significantly related to motor, cognitive, and psychiatric states, suggesting that it may bridge the correlative gap between psychiatric and cognitive states in HD. CONCLUSION: SPS may be worth assessing in conjunction with the standard gamut of clinical assessments in HD. Suggestions for future research and implications for patients, families, caregivers, and clinicians are discussed.

Usefulness of the Montreal Cognitive Assessment (MoCA) in Huntington's disease.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is a brief screening instrument for dementia that is sensitive to executive dysfunction. This study examined its usefulness for assessing cognitive performance in mild, moderate, and severe Huntington's disease (HD), compared with the use of the Mini-Mental State Examination (MMSE). METHODS: We compared MoCA and MMSE total scores and the number of correct answers in 5 cognitive-specific domains in 104 manifest HD patients and 100 matched controls. RESULTS: For the total HD sample, and for the moderate and severe patients, significant differences between both MoCA and MMSE total scores and almost all cognitive-specific domains emerged. Even mild HD subjects showed significant differences with regard to total score and several cognitive domains on both instruments. CONCLUSIONS: We conclude that the MoCA, although not necessarily superior to the MMSE, is a useful instrument for assessing cognitive performance over a broad level of functioning in HD.

Cognitive performance on the mini-mental state examination and the montreal cognitive assessment across the healthy adult lifespan.

OBJECTIVE: We sought to compare age-related performance on the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) across the adult lifespan in an asymptomatic, presumably normal, sample. BACKGROUND: The MMSE is the most commonly used brief cognitive screening test; however, the MoCA may be better at detecting early cognitive dysfunction. METHODS: We gave the MMSE and MoCA to 254 community-dwelling participants ranging in age from 20 to 89, stratified by decade, and we compared their scores using the Wilcoxon signed rank test. RESULTS: For the total sample, the MMSE and MoCA differed significantly in total scores as well as in visuospatial, language, and memory domains (for all of these scores, P<0.001). Mean MMSE scores declined only modestly across the decades; mean MoCA scores declined more dramatically. There were no consistent domain differences between the MMSE and MoCA during the third and fourth decades; however, significant differences in memory (P<0.05) and language (P<0.001) emerged in the fifth through ninth decades. CONCLUSIONS: We conclude that the MoCA may be a better detector of age-related decrements in cognitive performance than the MMSE, as shown in this community-dwelling adult population.

Postural limits of stability in premanifest and manifest Huntington's disease.

BACKGROUND: Huntington's disease (HD) is associated with neuronal death in basal ganglia circuits important for postural control. Despite evidence of postural instability associated with HD, postural control at the limits of stability has not been investigated in this disease. OBJECTIVE: To use computerized dynamic posturography to measure postural control at the limits of stability during the premanifest and manifest stages of HD. METHODS: Patients with manifest HD, premanifest gene carriers, and matched controls stood on mechanically locked force plates while viewing a computer screen. The participant's estimated center of gravity was represented on the screen as a cursor along with eight target icons arranged in a circular pattern at the theoretical edge of limits of stability. On each trial, one of the eight targets was highlighted and the participant was instructed to control the cursor by rapidly shifting his/her weight in the direction of the target. Measures included reaction time, movement velocity, endpoint excursion, maximum excursion, and directional control. RESULTS: Analysis of variance revealed significant impairment on endpoint excursion, maximum excursion, and directional control (p≤0.001) in the Huntington's disease group, but not in the premanifest gene carrier group as compared to controls. No differences were found on reaction time or movement velocity measures. Group signal to noise ratios also were examined for the measures. CONCLUSIONS: HD patients, but not premanifest gene carriers, showed impaired postural control at the limits of stability. Impaired performance in HD patients has potential functional consequences including increased risk of falling during weight-shifting activities.

Neural stem cell depletion and CNS developmental defects after enteroviral infection.

Coxsackieviruses are significant human pathogens causing myocarditis, meningitis, and encephalitis. We previously demonstrated the ability of coxsackievirus B3 (CVB3) to persist within the neonatal central nervous system (CNS) and to target neural stem cells. Given that CVB3 is a cytolytic virus and may therefore damage target cells, we characterized the potential reduction in neurogenesis within the developing brain and the subsequent developmental defects that occurred after the loss of these essential neural stem cells. Neonatal mice were inoculated with a recombinant CVB3 expressing eGFP (eGFP-CVB3), and alterations in neurogenesis and brain development were evaluated over time. We observed a reduction in proliferating cells in CNS neurogenic regions simultaneously with the presence of nestin(+) cells undergoing apoptosis. The size of the brain appeared smaller by histology, and a permanent decrease in brain wet weight was observed after eGFP-CVB3 infection. We also observed an inverse relationship between the amount of virus material and brain wet weight up to day 30 postinfection. In addition, signs of astrogliosis and a compaction of the cortical layers were observed at 90 days postinfection. Intriguingly, partial brain wet weight recovery was observed in mice treated with the antiviral drug ribavirin during the persistent stage of infection. Hence, long-term neurological sequelae might be expected after neonatal enteroviral infections, yet antiviral treatment initiated long after the end of acute infection might limit virus-mediated neuropathology.