Implicit and explicit aspects of sequence learning in pre-symptomatic Huntington's disease.

Learning deficits may be part of the early symptoms of Huntington's disease (HD). Here we characterized implicit and explicit aspects of sequence learning in 11 pre-symptomatic HD gene carriers (pHD) and 11 normal controls. Subjects moved a cursor on a digitizing tablet and performed the following tasks: SEQ: learning to anticipate the appearance of a target sequence in two blocks; VSEQ: learning a sequence by attending to the display without moving for one block, and by moving to the sequence in a successive block (VSEQ test). Explicit learning was measured with declarative scores and number of anticipatory movements. Implicit learning was measured as a strategy change reflected in movement time. By the end of SEQ, pHD had a significantly lower number of correct anticipatory movements and lower declarative scores than controls, while in VSEQ and VSEQ test these indices improved. During all three tasks, movement time changed in controls, but not in pHD. These results suggest that both explicit and implicit aspects of sequence learning may be impaired before the onset of motor symptoms. However, when attentional demands decrease, explicit, but not implicit, learning may improve.

Thalamic metabolism and symptom onset in preclinical Huntington's disease.

The neural basis for the transition from preclinical to symptomatic Huntington's disease (HD) is unknown. We used serial positron emission tomography (PET) imaging in preclinical HD gene carriers (p-HD) to assess the metabolic changes that occur during this period. Twelve p-HD subjects were followed longitudinally with [11C]-raclopride and [18F]-fluorodeoxyglucose PET imaging, with scans at baseline, 18 and 44 months. Progressive declines in striatal D2-receptor binding were correlated with concurrent changes in regional metabolism and in the activity of an HD-related metabolic network. We found that striatal D2 binding declined over time (P < 0.005). The activity of a reproducible HD-related metabolic covariance pattern increased between baseline and 18 months (P < 0.003) but declined at 44 months (P < 0.04). These network changes coincided with progressive declines in striatal and thalamic metabolic activity (P < 0.01). Striatal metabolism was abnormally low at all time points (P < 0.005). By contrast, thalamic metabolism was elevated at baseline (P < 0.01), but fell to subnormal levels in the p-HD subjects who developed symptoms. These findings were confirmed with an MRI-based atrophy correction for each individual PET scan. Increases in network expression and thalamic glucose metabolism may be compensatory for early neuronal losses in p-HD. Declines in these measures may herald the onset of symptoms in gene carriers.

Cognitive and behavioral dysfunction in Parkinson's disease: neurochemical and clinicopathological contributions.

The cognitive and behavioral sequelae (i.e., nonmotor profile) of Parkinson's disease (PD), with executive dysfunction and depression being most prominent, have typically been overshadowed due to an emphasis on motor symptomatology. The apparent categorization of PD as a disorder isolated to the dopaminergic system may be a generalization of the disease pathology. Dopamine therapy, used for the treatment of motor symptoms, has not consistently been shown to resolve nonmotor impairments. Research evidence indicates that nondopaminergic neurotransmitter systems (i.e., serotonergic, noradrenergic, & cholinergic) are disrupted in PD and may contribute to cognitive and behavioral dysfunction. Furthermore, Lewy bodies within cortical and subcortical structures can add to the nonmotor profile in PD. Pharmacological interventions for the treatment of cognitive and behavioral impairments associated with PD are few, especially for nondemented patients. The current review of the literature highlights evidence that associates nonmotor dysfunctions with neurochemical and clinicopathological correlates of PD.

Evaluation of practice effects in language and spatial processing test performance.

Recent research demonstrates that practice effects are attenuated through the administration of alternate-form memory tests. However, little is known about the degree of practice that can be expected when alternate forms of nonmemory tests are administered repeatedly. Two groups of healthy older adults were assigned to either a same- or alternate-forms condition. Participants completing the same forms of a confrontation naming task improved significantly over 4 testing sessions. On verbal fluency, participant performance significantly improved when completing only alternate forms. No significant practice effects were observed on tests of spatial processing. Practice effects caused by item-specific practice may be reduced via alternate test forms. However, similar reductions will be less apparent when practice effects are the result of test-specific practice.

Practice effects during repeated administrations of memory tests with and without alternate forms.

Previous research indicates that practice effects are large with repeated versions of memory tests. In contrast, administrations of the same tests using alternate forms typically yield much smaller practice effects. However, most studies do not compare alternate- and same-form conditions directly, and differ widely in terms of test-retest interval, modality of stimuli (verbal, spatial), format of the memory test, and number of examinations. The present study investigated practice effects during repeated administrations of verbal and nonverbal memory tests which have the same administration format. Two groups of healthy participants, matched for age, education, estimated IQ, and baseline memory test performance, were assigned to either a same- or alternate-forms condition. Participants taking the same form every two weeks improved significantly over four sessions. Participants completing alternate forms of the nonverbal memory test produced a small practice gain, but the verbal memory test was resistant to practice effects when alternate forms were used.

Normative data for equivalent, parallel forms of the Judgment of Line Orientation Test.

The Judgment of Line Orientation Test (JLO; Benton, Hamsher, Varney, & Spreen, 1983) permits assessment of visuospatial processing without making demands on motor skills. However, its administration can be time-intensive and frustrating for patients, particularly when used in a geriatric population. We present a single set of normative data to be used for both the odd-item and even-item forms derived from Form V of the JLO based on responses from a healthy geriatric sample. Mean scores and distributions of odd-item and even-item forms were nearly identical, and both forms showed significant correlations with the Developmental Test of Visual- Motor Integration. Cross-validation using the odd form of the JLO on an independent sample from a different geographic location suggested good generalizability of the normative data. We conclude that these JLO short-form normative data may be used in clinical screening situations or when serial assessments are needed.