Joanne Green

Cognitive impairments in advanced PD without dementia

Objective: To determine the nature and frequency of cognitive impairments in nondemented patients with advanced PD and their relationship to other variables potentially predictive of neuropsychological performance. Methods: The neuropsychological performance of nondemented, nondepressed patients with idiopathic PD (n = 61) was quantified with respect to clinically available normative data. The relationship of neuropsychological measures to motor symptoms, age, years of education, disease duration, age at disease onset, disease deterioration rate, and dopaminergic therapy was assessed. Results: Impairment was most frequent on measures sensitive to frontal lobe function (67% on Wisconsin Card Sorting Test number of categories, 30% on letter fluency, 30% on verbal learning). Poorer performance on multiple neuropsychological measures was related to greater overall motor abnormality (total Unified Parkinson’s Disease Rating Scale score), increased bradykinesia on medication, older age, longer disease duration, and reduced education. Conclusions: Even in the absence of dementia or depression, patients with advanced PD are likely to show clinically significant impairments on neuropsychological measures sensitive to changes in dorsolateral prefrontal regions participating in cognitive basal ganglia-thalamocortical circuits.

Tau pathology in a family with dementia and a P301L mutation in tau

Familial forms of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) have recently been associated with coding region and intronic mutations in the tau gene. Here we report our findings on 2 affected siblings from a family with early-onset dementia, characterized by extensive tau pathology and a Pro to Leu mutation at codon 301 of tau. The proband, a 55-year-old woman, and her 63-year-old brother died after a progressive dementing illness clinically diagnosed as Alzheimer disease. Their mother, 2 sisters, maternal aunt and uncle, and several cousins were also affected. Autopsy in both cases revealed frontotemporal atrophy and degeneration of basal ganglia and substantia nigra. Sequencing of exon 10 of the tau gene revealed a C to T transition at codon 301, resulting in a Pro to Leu substitution. Widespread neuronal and glial inclusions, neuropil threads, and astrocytic plaques similar to those seen in corticobasal degeneration were labeled with a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes spanning the entire tau sequence. Isolated tau filaments had the morphology of narrow twisted ribbons. Sarkosyl-insoluble tau exhibited 2 major bands of 64 and 68 kDa and a minor 72 kDa band, similar to the pattern seen in a familial tauopathy associated with an intronic tau mutation. These pathological tau bands predominantly contained the subset of tau isoforms with 4 microtubule-binding repeats selectively affected by the P301L missense mutation. Our findings emphasize the phenotypic and genetic heterogeneity of tauopathies and highlight intriguing links between FTDP-17 and other neurodegenerative diseases.

Treatment of advanced Parkinson's disease by unilateral posterior GPi pallidotomy: 4-year results of a pilot study.

To assess the long‐term outcome following unilateral pallidotomy for advanced Parkinsons disease, we performed nonblinded Core Assessment Program for Intracerebral Transplantations protocol assessments in 10 of the original 15 patients in our pilot study for 4 years following surgery. Although Unified Parkinsons Disease Rating Scale motor examination scores returned to baseline levels at 3 and 4 years, most patients continued to show sustained improvements in contralateral tremor, akinesia, and drug‐induced dyskinesias. Contralateral tremor was absent at 4 years in all seven patients with preoperative tremor. Contralateral “off” arm movement times (averaged for three tasks) decreased by 37% at 1 year and by 30% at 4 years. Contralateral dyskinesia scores improved by 82% at 1 year and by 64% at 4 years. In contrast, after reaching speeds equal to the contralateral side at 1 year, ipsilateral “off” movement times increased by 13% over baseline levels at 4 years. Although most gait and postural stability measures showed modest initial improvement followed by a return to baseline values, “on” stand–walk–sit task performance declined significantly at 4 years. Despite the restriction of our surgeries to one side and the expected natural progression of Parkinsons disease, the results of patient self‐assessments suggest that 4 years after unilateral pallidotomy, most patients continue to experience a quality of life above preoperative levels.

Tactile spatial acuity and roughness discrimination: Impairments due to aging and Parkinson's disease

We used gratings of alternating ridges and grooves in a quantitative psychophysical investigation of tactile perception in patients with Parkinsons disease (PD) and age-matched normal controls. The groove width required for threshold discrimination of grating orientation was 25% higher in the control subjects compared to younger individuals studied previously(p = 0.004), indicating a small but significant decline in tactile spatial acuity with age. Relative to age-matched controls, patients with PD showed a twofold increase in the tactile spatial threshold (p = 3.07 × 10-8), with somewhat greater impairment on the side more affected clinically (p = 0.03). Testing with the forearm prone, as compared to supine, produced a small improvement in the acuity of patients (p = 0.01) but not controls (p = 0.26). PD patients were also impaired in tactually discriminating grating roughness: their difference limens were over three times higher than those of controls(p = 5.74 × 10-5) for gratings differing in groove width, and over twice as high (p = 0.0003) for gratings differing in ridge width. We conclude that PD significantly impairs performance on these tactile tasks.

Mood changes with deep brain stimulation of STN and GPi: results of a pilot study

The results of this study suggest that there are mood changes associated with deep brain stimulation of the subthalamic nucleus (STN) and the globus pallidus interna (GPi). Further, optimal placement of electrodes in both STN and GPi seems to result in overall improvement in mood and is associated with a lower incidence of adverse mood effects than stimulation outside the optimal site. Preliminary data from this study, however, suggest that slight movement dorsal or ventral to the site of optimal motor performance may be associated with more adverse changes in mood with STN stimulation than with GPi stimulation.

Cognitive, Behavioral, and Physiological Changes in Alzheimer Disease Patients as a Function of Incontinence Medications

OBJECTIVE Authors evaluated the cognitive, neurophysiologic, and behavioral effects of incontinence medications in patients with Alzheimer disease (AD). METHODS Nine patients were evaluated, both on and off incontinence medication, for cognitive status, neuropsychiatric status, activities of daily living, and serum anticholinergic level. Caregivers were interviewed to evaluate behavioral status and caregiver burden. RESULTS Patients showed better performance on specific measures of cognition and behavior when not taking medication for incontinence. A significant, inverse correlation was found between mental status and anticholinergic level. CONCLUSION Although the sample size was small, the findings suggest that, in patients with AD, incontinence medications with anticholinergic properties may have detrimental effects on mental status and behavior.

Neuropsychological and psychiatric sequelae of pallidotomy for PD: Clinical trial findings

ObjectiveTo evaluate the neuropsychological and psychiatric sequelae of unilateral posterior pallidotomy for treatment of PD. MethodsPatients with idiopathic PD completed baseline and 3- and 6-month assessments after random assignment to an immediate surgery (n = 17) or medical management (n = 16) group. ResultsCompared with the medical management group, the immediate surgery group with single lesions centered on the posterior internal pallidum showed superior naming and response inhibition, better verbal recall at 6 months, but greater distractibility, a tendency toward lower phonemic fluency, and a transient (3 months’ only) semantic fluency deficit. The group with left lesions had more neuropsychological deficits than the group with right lesions or the medical management group, although these occurred mainly at 3 (but not 6) months. At 6 months, the patients with left lesions showed better verbal memory retention than the patients with right lesions. On most measures, the pattern of individual clinical change did not differ as a function of surgery or lesion laterality, with the exception of a higher frequency of decline in phonemic fluency in the patients with left lesions at 6 months. Although psychiatric status did not change overall, a history of depression tended to increase the risk of a depressive episode following surgery. ConclusionsWell-targeted, uncomplicated, unilateral pallidotomy does not produce overall neuropsychological or psychiatric change, although there are subtle changes on specific measures sensitive to frontal lobe function.

Dysnomia in Alzheimer's disease: An evaluation of neurobehavioral subtypes ☆

The relative influence of perceptual and semantic features on naming performance was investigated with reference to the neurobehavioral profiles displayed by patients with Alzheimers disease (AD). Forty-one patients were classified as manifesting a verbal, visual, or global subtype based upon their pattern of neuropsychological functioning. Perceptual characteristics of to-be-named pictures were varied by manipulating the amount of line detail, whereas semantic qualities were varied by altering word frequency norms. All AD subtypes were less accurate than normal elderly controls in naming low frequency pictures. Patients and controls took longer to name low frequency and high complexity pictures, and this effect was comparable across the AD groups. Patients with predominantly visual deficits were significantly slower in naming than controls, and those with verbal impairments made a higher proportion of semantic naming errors when compared to patients displaying visual or severe global impairments. These results suggest that deficits in semantic processing contribute to naming dysfunction in AD, and they highlight the importance of examining dissociations among neurobehavioral subtypes.

Memory evaluation in older adults

When older individuals are referred for neuropsychological evaluation, the most common concern is memory dysfunction. This chapter briefly reviews the current models of memory systems within the brain and processing activities fundamental to remembering, to establish a conceptual framework for the clinical evaluation of memory. Research in neuroscience has revealed that remembering is not dependent on a single brain region or brain system but instead reflects the functioning of several neuroanatomically distinct and separable systems within the brain that modulate fundamentally different types of long-term memory. From a cognitive perspective, the major components of these systems are declarative memory and nondeclarative memory. Declarative memory is dependent on a neural system including three interrelated brain regions: the medial temporal lobe, proximal areas within the brain stem known as the diencephalon, and an area just anterior to the diencephalon known as the basal forebrain. Although disorders affecting the neuropsychological status of older adults may have distinctive effects on declarative as compared with nondeclarative memory, clinical evaluation typically focuses on the evaluation of declarative memory. During formal testing, the patients abilities to acquire, store, and retrieve information in memory are evaluated. In addition, the test battery evaluates several other fundamental dimensions of memory function.

Organizing and interpreting test findings

This chapter summarizes the sequence of activities that can be applied to organizing and interpreting the test findings. These activities include computing the raw test scores, comparing the test scores with normative data to obtain standardized scores, compiling the data summary sheet, determining estimates of pre-morbid abilities, interpreting test scores, identifying the neuropsychological profile and disorders associated with this profile, and identifying change on reevaluation. Total raw scores for each test are computed by using the standardized instructions provided in the test manuals, which are then compared with the normative data to determine if the scores are within normal limits for the sample from which the normative data were derived. The next step is to summarize the raw test and standard scores by entering them in a data sheet. The data sheet includes columns for entering the raw scores, the standard scores provided in the test manual, the z-score conversions of the standard scores, premorbid estimates of abilities, interpretations of test scores, and qualitative comments concerning test performance. Determining an estimate of premorbid ability is a critical step, since this estimate is used as a standard to determine whether the patient has experienced significant decline in neuropsychological function. It is recommended that estimates of premorbid intelligence be applied as one basis for estimating abilities within specific neuropsychological domains. Each test score is then interpreted within the context of the normative data or within the context of the patients premorbid abilities.