Bryan Bernard

Effect of donepezil on motor and cognitive function in Huntington disease

Striatal cholinergic dysfunction may be important in Huntington disease (HD). We studied whether donepezil improves chorea, cognition, and quality of life (QoL) in HD. Thirty patients were randomly assigned to treatment with donepezil or placebo. At the doses studied, donepezil did not improve chorea, cognition, or QoL. Adverse events were similar between both groups. Based on this small sample study, donepezil was not an effective treatment for HD.

Use of the national adult reading test to estimate premorbid iq in dementia

Two methods for estimating premorbid IQ were employed in a sample of 199 dementia patients and 26 control subjects: (1) the National Adult Reading Test (NART), a present ability measure, and (2) an age, sex, race, education and occupation regression formula-a demographically based estimate. The dementia sample consisted of probable Alzheimers disease, multi-inf arct dementia and a mixture of the two. Controls consisted of the spouses of the patient sample. The patient sample was divided into three levels of dementia severity equated for age and level of education. The NART estimates in the mild and moderate/severe dementia groups differed significantly from those for the very mildly demented patients and controls. The results suggest that the applicability of the NART in estimating premorbid IQ in dementia may be limited.

GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease

Loss‐of‐function mutations in the GBA gene are associated with more severe cognitive impairment in PD, but the nature of these deficits is not well understood and whether common GBA polymorphisms influence cognitive performance in PD is not yet known.

Clinical differences among mild cognitive impairment subtypes in Parkinson’s disease

Mild cognitive impairment is increasingly recognized as a construct in Parkinsons disease (PD) and occurs in about 25% of nondemented PD patients. Although executive dysfunction is the most frequent type of cognitive deficit in PD, the cognitive phenotype of PD mild cognitive impairment (PD‐MCI) is broad. PD‐MCI subtypes are represented by amnestic and nonamnestic domain impairment as well as single‐ and multiple‐domain impairment. However, it is unclear whether patients with different PD‐MCI subtypes also differ in other clinical characteristics in addition to cognitive profile. We studied 128 PD‐MCI subjects at our Movement Disorders center, comparing clinical, motor, and behavioral characteristics across the PD‐MCI subtypes. We found varying proportions of impairment subtypes: nonamnestic single domain, 47.7%; amnestic multiple domain, 24.2%; amnestic single domain, 18.8%; and nonamnestic multiple domain, 9.5%. Attentional/executive functioning and visuospatial abilities were the most frequently impaired domains. PD‐MCI subtypes differed in their motor features, with nonamnestic multiple‐domain PD‐MCI subjects showing particularly pronounced problems with postural instability and gait. Differences among PD‐MCI subtypes in age, PD duration, medication use, mood or behavioral disturbances, and vascular disease were not significant. Thus, in addition to differing cognitive profiles, PD‐MCI subtypes differed in motor phenotype and severity but not in mood, behavioral, or vascular comorbidities. Greater postural instability and gait disturbances in the nonamnestic multiple‐domain subtype emphasize shared nondopaminergic neural substrates of gait and cognition in PD. Furthermore, increased burden of cognitive dysfunction, rather than type of cognitive deficit, may be associated with greater motor impairment in PD‐MCI.

The Montreal Cognitive Assessment as a screening tool for cognitive dysfunction in Huntington's disease.

Cognitive dysfunction is one of the hallmarks of Huntingtons disease (HD) and may precede the onset of motor symptoms. The Montreal Cognitive Assessment (MoCA), a brief cognitive screening instrument with high specificity and sensitivity for detecting early cognitive impairments, has not been studied in the HD population. In this study, we compare the MoCA with the mini‐mental state examination (MMSE) as a screening tool for cognitive dysfunction among 53 patients with HD. The mean MMSE score was 26 ± 2.4, and mean MoCA score was 21 ± 4.4. Twenty‐one patients (81%) of those who scored ≥26 on the MMSE had the MoCA score <26. Thirty‐two patients (78%) of those who scored ≥24 on the MMSE had the MoCA score <24. The MoCA may be a more sensitive screening tool for cognitive impairments in HD relative to the MMSE.

The effect of unilateral electrostimulation of the subthalamic nucleus on respiratory/ phonatory subsystems of speech production in Parkinson's disease: a preliminary report

This paper reports findings on the respiratory/phonatory subsystems from an on‐going study investigating the effect of unilateral electrostimulation of the subthalamic nucleus (STN) on different speech subsystems in people with Parkinsons disease (PD). Speech recordings were made in the medication‐off state at baseline, three months post surgery with stimulation‐on, and with stimulation‐off, in six right‐handed PD patients. Subjects completed several speech tasks. Acoustic analyses of the maximally sustained vowel phonation were reported. The results were compared to the scores of the motor section of the Unified Parkinsons Disease Rating Scale (UPDRS‐III) obtained under the same conditions. Results showed that stimulation‐on improved UPDRS‐III scores in all six subjects. While mild improvement was observed for all subjects in the Stimulation‐on condition, three subjects received left‐STN stimulation showed a significant decline in vocal intensity and vowel duration from their baseline indicating the speech function was very susceptible to micro lesions due to the surgical procedure itself when the surgical site was in the dominant hemisphere.

Defining optimal cutoff scores for cognitive impairment using Movement Disorder Society Task Force criteria for mild cognitive impairment in Parkinson's disease

The recently proposed Movement Disorder Society (MDS) Task Force diagnostic criteria for mild cognitive impairment in Parkinsons disease (PD‐MCI) represent a first step toward a uniform definition of PD‐MCI across multiple clinical and research settings. However, several questions regarding specific criteria remain unanswered, including optimal cutoff scores by which to define impairment on neuropsychological tests. Seventy‐six non‐demented PD patients underwent comprehensive neuropsychological assessment and were classified as PD‐MCI or PD with normal cognition (PD‐NC). The concordance of PD‐MCI diagnosis by MDS Task Force Level II criteria (comprehensive assessment), using a range of standard deviation (SD) cutoff scores, was compared with our consensus diagnosis of PD‐MCI or PD‐NC. Sensitivity, specificity, and positive and negative predictive values were examined for each cutoff score. PD‐MCI subtype classification and distribution of cognitive domains impaired were evaluated. Concordance for PD‐MCI diagnosis was greatest for defining impairment on neuropsychological tests using a 2 SD cutoff score below appropriate norms. This cutoff also provided the best discriminatory properties for separating PD‐MCI from PD‐NC compared with other cutoff scores. With the MDS PD‐MCI criteria, multiple domain impairment was more frequent than single domain impairment, with predominant executive function, memory, and visuospatial function deficits. Application of the MDS Task Force PD‐MCI Level II diagnostic criteria demonstrates good sensitivity and specificity at a 2 SD cutoff score. The predominance of multiple domain impairment in PD‐MCI with the Level II criteria suggests not only influences of testing abnormality requirements, but also the widespread nature of cognitive deficits within PD‐MCI.

Effects of language disturbances on premorbid estimates of IQ in mild dementia

Two methods were used to estimate premorbid IQ in a sample of 68 patients with mild dementia: (1) the National Adult Reading Test (NART), a present ability measure, and (2) an age, sex, race, education and occupation regression formula, a demographically based estimate (DIQ). The dementia sample consisted of probable Alzheimers disease, multi-infarct dementia and a mixture of the two. The sample was divided into three levels of language disturbances (no language disturbance, naming or fluency disturbance, or both naming and fluency disturbance) based upon performance on the Visual Naming test and the Controlled Oral Word Association test. The NART IQ estimates in patients with one or more language disturbances were significantly lower than those in patients without language disturbances despite equivalent DIQ and Mini-Mental Status exam performance. The results suggest that the applicability of the NART to dementia patients with prominent language disturbances is limited.

Diagnosing PD-MCI by MDS Task Force criteria: how many and which neuropsychological tests?

The optimal properties of a comprehensive (level II) neuropsychological battery for determining Parkinsons disease mild cognitive impairment (PD‐MCI) by Movement Disorder Society (MDS) Task Force criteria remain unresolved.

Clinical validation of movement disorder society–recommended diagnostic criteria for Parkinson's disease with dementia

The objective of this work was to evaluate the Movement Disorders Society (MDS) Task Force–proposed screening checklist for detecting Parkinsons disease dementia (PD‐D) in relation to full neuropsychological testing. An MDS Task Force has proposed diagnostic procedures for PD‐D, which have not been fully validated against more extensive neuropsychological testing. PD subjects were recruited from 2 specialty centers. A neuropsychologist evaluated them for dementia as part of routine clinical care. Independent clinical neurologists administered the MDS PD‐D screening checklist. Diagnosis of PD‐D by the 2 methods was compared. Ninety‐one PD subjects had a mean age of 66.3 (SD = 9.7) years and a mean PD duration of 8.8 (SD = 6.1) years. Seven subjects (7.7%) met all 8 screening checklist criteria from the MDS PD‐D screening tool and were classified as probable PD‐D. Fifteen (16.5%) subjects were classified as PD‐D by full neuropsychological assessment. The screening checklist showed 100% specificity, but only 46.7% sensitivity, for diagnosing PD‐D compared to the full neuropsychological assessment. PD‐D cases missed by the PD‐D screening tool were largely due to 2 checklist items that were not endorsed (absence of depression and Mini‐Mental State Examination [MMSE] scores <26). There was moderate agreement between these 2 methods for determination of PD‐D (kappa = 0.59, P < .001). The MDS‐PD‐D screening checklist is highly accurate for detecting PD‐D if all items are endorsed. However, for cases that do not meet these criteria, full neuropsychological testing is needed to differentiate PD‐D from milder cognitive impairment. Revision of the checklist by altering or eliminating the 2 problematic checklist items may improve sensitivity.