John C. Dalrymple-Alford

The MoCA Well-suited screen for cognitive impairment in Parkinson disease

Objective: To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales for Outcomes in Parkinson disease–Cognition [SCOPA-COG]) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks. Methods: A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N). Results: Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve [AUC], 87%–91%) and PD-MCI from PD-N patients (AUC, 78%–90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value [NPV] 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval [CI] 70%–89%; SCOPA-COG 74%, CI 62%–86%; MMSE-Sevens item 56%, CI 44%–68%; MMSE-World item 62%, CI 50%–73%). Conclusions: The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD.

Long term psychosocial outcomes after mild head injury in early childhood

Objectives: The question of whether any adverse cognitive or psychosocial outcomes occur after mild head injury in early childhood has evoked considerable controversy. This study examined mild head injury before age 10 and potential differences in late childhood/early adolescence as a function of severity of mild injury and age at injury. Methods: A fully prospective longitudinal design tracked a large birth cohort of children. Confirmed cases of mild head injury before age 10 were divided on the basis of outpatient medical attention (n=64–84) or inpatient observation (hospital overnight; n=26–28 ) and compared with the non-injured remainder of the cohort (reference group; n=613–807). A range of pre-injury and post-injury child and family characteristics were used to control for any potential confounds. Outcome after injury before and after age 5 was also assessed. Results: After accounting for several demographic, family, and pre-injury characteristics, the inpatient but not the outpatient group displayed increased hyperactivity/inattention and conduct disorder between ages 10 to 13, as rated by both mothers and teachers. Psychosocial deficits were more prevalent in the inpatient subgroup injured before age 5. No clear effects were evident for various cognitive/academic measures, irrespective of severity of mild injury or age at injury. Conclusions: Most cases of mild head injury in young children do not produce any adverse effects, but long term problems in psychosocial function are possible in more severe cases, perhaps especially when this event occurs during the preschool years. The view that all mild head injuries in children are benign events requires revision and more objective measures are required to identify cases at risk.

Both anteromedial and anteroventral thalamic lesions impair radial-maze learning in rats.

Disruption to the anterior thalamus (AT) may be an important factor in diencephalic amnesia. Rats with small lesions of the anteromedial (AM) or anteroventral (AV) nucleus showed persistent working-memory and reference-memory deficits in a 12-arm radial maze, although they were comparable to controls during the early part of training. The only activity difference in the maze was that lesioned rats failed to run more slowly when revisiting a baited arm. For all groups, both working and reference memory were impaired after extramaze cues were removed; removal of intramaze cues further impaired performance relative to the original conditions. These findings suggest the AT makes a distinct contribution to mnemonic functions, probably as part of an integrated system involving limbic cortex and the hippocampal formation, and that AT lesions produce a general rather than a specific deficit in spatial or working memory.

Brain plasticity, learning, and memory

Ivan Divac and Jesper Mogensen Institute of Neurophysiology University of Copenhagen School of Medicine The present chapter offers in a capsular form a concept of organization of the non-limbic division of the mammalian forebrain. We first draw attention to certain structural and functional properties of the prosencephalon and conclude that interrelated parts of the thalamus, isocortex and neostriatum constitute functional systems. In the next step we attribute to these systems distinct properties which can be related to well established psychological phenomena. Finally, one of testable predictions is presented.

Dissociable memory effects after medial thalamus lesions in the rat

Variable neuropathology in cases of diencephalic amnesia has led to uncertainty in identifying key thalamic nuclei and their potential role in learning and memory. Based on the principal neural connections of the medial thalamus, the current study tested the hypothesis that different aggregates of thalamic nuclei contribute to separate memory systems. Lesions of the anterior thalamic aggregate (AT), which comprises the anterodorsal, anteromedial and anteroventral nuclei produced substantial deficits in both working and reference spatial memory in a radial arm maze task in rats, supporting the view that the AT is an integral part of a hippocampal memory system. Lesions to the lateral thalamic aggregate (LT), which comprises the intralaminar nuclei (centrolateral, paracentral and rostral central medial nuclei) and lateral mediodorsal thalamic nuclei (lateral and paralamellar nuclei) produced a mild working memory impairment only, while lesions to the posteromedial thalamic aggregate (MT), which comprises the central and medial mediodorsal thalamic nuclei and the intermediodorsal nucleus had no effect on radial arm maze performance. In contrast, only MT lesions impaired learning associated with memory for reward value, consistent with the idea that the MT contributes to an amygdala memory system. Compared with chance discrimination, the control and AT groups, but not MT or LT groups, showed evidence for temporal order memory for two recently presented objects; all groups showed intact object recognition for novel vs. familiar objects. These new dissociations show that different medial thalamic aggregates participate in multiple memory systems and reinforce the idea that memory deficits in diencephalic amnesics may vary as a function of the relative involvement of different thalamic regions.

Motor deficits and recovery during the first year following mild closed head injury

Objective: This study examined motor impairments over 1 year following mild closed head injury (CHI). It is the first study to serially assess long-term oculomotor and upper-limb visuomotor function following mild head trauma. Methods: Thirty-seven patients with mild CHI and 37 matched controls were compared at 1 week, 3 months and 6 months and 31 available pairs at 12 months post-injury on measures of saccades, oculomotor smooth pursuit, upper-limb visuomotor function and neuropsychological performance. Symptomatic recovery was sampled using the Rivermead Postconcussion Symptoms Questionnaire. Results: At 1 week, the group with CHI reported high levels of post-concussional symptoms and exhibited prolonged saccade latencies, increased directional errors, decreased saccade accuracy and impaired fast sinusoidal smooth pursuit concomitant with increased arm movement reaction time, decreased arm movement speed and decreased motor accuracy on upper-limb visuomotor tracking tasks. Neuropsychological testing identified deficits only in verbal learning and speed of processing while attention, short-term/working memory and general cognitive performance were preserved. At 3 and 6 months, the group with CHI continued to show deficits on several oculomotor and upper-limb visuomotor measures in combination with some deficits on verbal learning and improved, yet abnormal, levels of post-concussional symptoms. At 12 months, the group with CHI had no cognitive impairment but residual deficits in eye and arm motor function and continued to show elevated levels of post-concussional symptoms. Conclusions: The findings indicate that multiple motor systems are measurably impaired up to 12 months following mild CHI and that instrumented motor assessment may provide sensitive and objective markers of cerebral dysfunction during recovery from mild head trauma independent of neuropsychological assessment and patient self-report.

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson’s disease

There is a need for objective imaging markers of Parkinsons disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinsons disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinsons disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinsons disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinsons disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinsons disease.

Characterizing mild cognitive impairment in Parkinson's disease†

There is growing interest in identifying Parkinsons disease (PD) patients with mild cognitive impairment (PD‐MCI), but widely disparate criteria have been used. We assessed 143 PD patients and 50 matched controls on 20 measures across 4 cognitive domains (executive function, attention and working memory, learning and memory, visuoperception). Twenty‐four patients met criteria for dementia (PD‐D); nondementia patients were classified as either with normal cognition or MCI for 12 neuropsychological criteria. We compared the influence of these criteria on the distribution of global cognitive performance in the resulting PD‐MCI groups relative to the control and PD‐D groups. Different criteria produced substantial variation in the proportion of PD‐MCI cases identified. Fourteen percent PD‐MCI was found when using 2 scores in 1 domain at 2 standard deviations (SD) below normative scores, with no controls identified as MCI, through to 89% PD‐MCI with 1 score in 1 domain at 1 SD below normative scores, when 70% of controls were identified as MCI. The balance of cases with impaired cognition but not those with generally intact cognition was better served by using criteria that required 2 specific deficit scores or deficits across 2 domains. As comparisons with external normative data may have greater applicability across centers, we suggest that 2 scores at −1.5 SD within any single domain (30% PD‐MCI) or 1 score at −1.5 SD in each of 2 domains (37% PD‐MCI) provide suitable criteria to minimize the inclusion of cognitively well patients. Clinical dementia rating did not improve the relative identification of cognitively impaired and unimpaired nondementia PD patients.

Characteristics of executive function impairment in Parkinson's disease patients without dementia.

Executive function impairments in Parkinsons disease (PD) are well documented. However, uncertainties remain regarding the impact of these deficits on other areas of cognitive functioning. The goal of this study was to provide a comprehensive assessment of cognitive characteristics in patients with PD without dementia and to assess how any such deficits affected other areas of cognitive functioning. Forty PD patients without dementia were compared to healthy controls using measures of attention and speed of processing and a comprehensive set of executive function tests including working memory, planning, and problem solving. Measures of memory/learning and visuospatial skills were also included to examine the relationship between aspects of executive function and other areas of cognition. Patients with PD showed deficits on measures of executive function, problem solving, and visuospatial skills. However, they were unimpaired on measures of planning, attention, and memory/learning. Deficits in problem solving were only evident for tasks with a high visuospatial content and were no longer significant when visuospatial skills were controlled for. While deficits in executive function and visuospatial skills were apparent for PD patients compared to controls, many aspects of cognition remained intact. These can provide a focus for cognitive intervention strategies that can be effective in delaying decline for PD patients.

Behavioral deficits after intrahippocampal fetal septal grafts in rats with selective fimbria-fornix lesions

SummaryFetal septal transplants have been shown to promote behavioral recovery in young adult rats with aspiration fimbria-fornix lesions, rats with septal lesions and in intact aged rats. The present study examined the behavioral impact of intrahippocampal septal cell suspension transplants (T) in young female rats that had received, 10 days earlier, either medial fimbria lesions (Group FI.T), dorsal (subcallosal) fornix lesions (Group FO.T) or these two lesions together (Group FIFO.T). Relative to rats with lesions only (groups FI, FO and FIFO), grafted rats, irrespective of lesion locus, displayed unexpected impairments in (i) a serial alternation learning task, 5 weeks and 6 months after transplantation, and (ii) in a radial maze, 7 months after transplantation. In the first alternation test, Group FIFO showed impaired performance relative to Groups FI, FO and the sham-operated controls (Group S). In the second alternation test, Groups FO.T and FO showed impaired performance relative to Groups FI.T and FI, and only the performance of Group FI did not differ from that of Group S. In the radial maze, Groups FI, FO and FIFO all showed impaired performance relative to Group S. By contrast, there were no deleterious effects of lesions or of grafts in the acquisition and retention of a step-through passive avoidance task, 10 weeks after transplantation. Our findings on the effects of selective fimbria-fornix lesions did not confirm the report that rats with FI lesions but not those with FO lesions are unable to learn a serial alternation task, nor the report that FO lesions impair passive avoidance retention. Acetylcholinesterase (AChE) histochemistry revealed that grafts were present but graft-derived innervation of the host hippocampus varied from extensive to almost non-existent in all transplant groups. AChE-positivity in the dorsal hippocampus (DH) was not related to behavioral performance. However, the grafts often grew to a considerable size within the host brain and in many rats, especially those in Group FI.T, produced moderate to extreme damage of the host DH. There was a significant positive correlation between errors in the radial maze and graft-induced DH damage but no relationship between errors and graft size. The results indicate that, after partial lesions of the fimbria-fornix, intrahippocampal septal grafts survive well but are likely to damage recipient structures and result in behavioral impairments.