C. Munro Cullum

Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sample

Objective: To provide normative and descriptive data for the Montreal Cognitive Assessment (MoCA) in a large, ethnically diverse sample. Methods: The MoCA was administered to 2,653 ethnically diverse subjects as part of a population-based study of cardiovascular disease (mean age 50.30 years, range 18–85; Caucasian 34%, African American 52%, Hispanic 11%, other 2%). Normative data were generated by age and education. Pearson correlations and analysis of variance were used to examine relationship to demographic variables. Frequency of missed items was also reviewed. Results: Total scores were lower than previously published normative data (mean 23.4, SD 4.0), with 66% falling below the suggested cutoff (<26) for impairment. Most frequently missed items included the cube drawing (59%), delayed free recall (56%; <4/5 words), sentence repetition (55%), placement of clock hands (43%), abstraction items (40%), and verbal fluency (38%; <11 words in 1 minute). Normative data stratified by age and education were derived. Conclusion: These findings highlight the need for population-based norms for the MoCA and use of caution when applying established cut scores, particularly given the high failure rate on certain items. Demographic factors must be considered when interpreting this measure.

Staging Dementia Using Clinical Dementia Rating Scale Sum of Boxes Scores: A Texas Alzheimer's Research Consortium Study

BACKGROUND The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score is commonly used, although the utility regarding this score in staging dementia severity is not well established. OBJECTIVE To investigate the effectiveness of CDR-SOB scores in staging dementia severity compared with the global CDR score. DESIGN Retrospective study. SETTING Texas Alzheimers Research Consortium minimum data set cohort. PARTICIPANTS A total of 1577 participants (110 controls, 202 patients with mild cognitive impairment, and 1265 patients with probable Alzheimer disease) were available for analysis. MAIN OUTCOME MEASURES Receiver operating characteristic curves were generated from a derivation sample to determine optimal cutoff scores and ranges, which were then applied to the validation sample. RESULTS Optimal ranges of CDR-SOB scores corresponding to the global CDR scores were 0.5 to 4.0 for a global score of 0.5, 4.5 to 9.0 for a global score of 1.0, 9.5 to 15.5 for a global score of 2.0, and 16.0 to 18.0 for a global score of 3.0. When applied to the validation sample, kappa scores ranged from 0.86 to 0.94 (P < .001 for all), with 93.0% of the participants falling within the new staging categories. CONCLUSIONS The CDR-SOB score compares well with the global CDR score for dementia staging. Owing to the increased range of values, the CDR-SOB score offers several advantages over the global score, including increased utility in tracking changes within and between stages of dementia severity. Interpretive guidelines for CDR-SOB scores are provided.

Schizophrenia and nicotinic receptors

&NA; Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition‐i.e., the brains ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short‐term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.

Magnetic resonance imaging of cerebellar–prefrontal and cerebellar–parietal functional connectivity

Recent studies of the cerebellum indicated its involvement in a diverse array of functions, and analyses of non-human primate neuroanatomy have revealed connections between cerebellum and cerebral cortex that might support cerebellar contributions to a wider range of functions than traditionally thought. These include cortico-ponto-cerebellar projections originating throughout cerebral cortex, in addition to projections from the dentate nucleus of the cerebellum to prefrontal and posterior parietal cortices via the thalamus. Such projections likely serve as important substrates for cerebellar involvement in human cognition, assuming their analogues are prominent in the human brain. These connections can be examined from a functional perspective through the use of functional connectivity MRI (FCMRI), a technique that allows the in vivo examination of coherence in MR signal among functionally related brain regions. Using this approach, low-frequency fluctuations in MR signal in the dentate nucleus correlated with signal fluctuations in cerebellar, thalamic, limbic, striatal, and cerebrocortical regions including parietal and frontal sites, with prominent coherence in dorsolateral prefrontal cortex. These findings indicate that FCMRI is a useful tool for examining functional relationships between the cerebellum and other brain regions, and they support the findings from non-human primate studies showing anatomic projections from cerebellum to regions of cerebral cortex with known involvement in higher cognitive functions. To our knowledge, this represents the first demonstration of functional coherence between the dentate nucleus and parietal and prefrontal cortices in the human brain, suggesting the presence of cerebellar-parietal and cerebellar-prefrontal functional connectivity.

Association between depression severity and neurocognitive function in major depressive disorder: a review and synthesis.

The effects of major depressive disorder (MDD) on neurocognitive function remain poorly understood. Results from published studies vary widely in terms of methodological factors, and very little is known about the effects of depression severity and other clinical characteristics on neurocognitive function. The purpose of this review was to synthesize prior research findings regarding neurocognitive functioning in patients with MDD and varying levels of depression severity and to provide recommendations for future directions. Overall, this review suggests that MDD has been inconsistently associated with neurocognitive functioning and there is limited understanding regarding the relationship between depression severity and neurocognitive sequelae. There was much heterogeneity on depression severity-related factors across studies assessing neurocognitive function in MDD, as well as substantial variability in the consideration of depression severity among studies, which suggests a need to further explore this important issue.

Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy

BACKGROUND Hippocampal volume reduction, declarative memory deficits, and cortisol elevations are reported in persons with major depressive disorder; however, data linking cortisol elevations with hippocampal atrophy are lacking. Prescription corticosteroid-treated patients offer an opportunity to examine corticosteroid effects on hippocampal volume and biochemistry and memory in humans. METHODS Seventeen patients on long-term prescription corticosteroid therapy and 15 controls of similar age, gender, ethnicity, education, height, and medical history were assessed with magnetic resonance imaging and proton magnetic resonance spectroscopy, the Rey Auditory Verbal Learning Test, Stroop Color Word Test and other neurocognitive measures, the Hamilton Rating Scale for Depression, Young Mania Rating Scale, and Brief Psychiatric Rating Scale. RESULTS Compared with controls, corticosteroid-treated patients had smaller hippocampal volumes and lower N-acetyl aspartate ratios, lower scores on the Rey Auditory Verbal Learning Test and Stroop Color Word Test, and higher Hamilton Rating Scale for Depression and Brief Psychiatric Rating Scale scores. CONCLUSIONS Patients receiving chronic corticosteroid therapy have smaller hippocampal volumes, lower N-acetyl aspartate ratios, and declarative memory deficits compared with controls. These findings support the idea that corticosteroid exposure appears to be associated with changes in hippocampal volume and functioning in humans.

Fmri of working memory in patients with mild cognitive impairment and probable Alzheimer's disease

The goals of this study were to evaluate brain activation in patients with probable Alzheimer’s disease (AD), mild cognitive impairment (MCI), and controls while performing a working memory (WM) task. Eleven AD patients, ten MCI subjects, and nine controls underwent functional magnetic resonance imaging (fMRI) while performing a visual WM task. Statistical parametric maps of brain activation were obtained in each group, and group activation difference maps were generated. Ability to perform the task did not differ among the groups. Activation was observed in the parahippocampal region, superior-middle-inferior frontal gyri, parietal region, anterior–posterior cingulate, fusiform gyrus, and basal ganglia. MCI and AD groups showed more activation than the controls in the right superior frontal gyrus, bilateral middle temporal, middle frontal, anterior cingulate, and fusiform gyri. Activation in the right parahippocampal gyrus, left inferior frontal gyrus, bilateral cingulate and lingual gyri, right lentiform nucleus, right fusiform gyrus, and left supramarginal gyrus in the AD group was less than in the MCI group. The WM task evoked activation in widely distributed regions, consistent with previous fMRI studies. AD and MCI patients showed an increased extent of activation and recruitment of additional areas.

Neuroimaging of Cognitive Dysfunction and Depression in Aging Retired National Football League Players: A Cross-sectional Study

OBJECTIVES To assess cognitive impairment and depression in aging former professional football (National Football League [NFL]) players and to identify neuroimaging correlates of these dysfunctions. DESIGN We compared former NFL players with cognitive impairment and depression, cognitively normal retired players who were not depressed, and matched healthy control subjects. SETTING Research center in the North Texas region of the United States. PATIENTS Cross-sectional sample of former NFL players with and without a history of concussion recruited from the North Texas region and age-, education-, and IQ-matched controls. Thirty-four retired NFL players (mean age, 61.8 years) underwent neurological and neuropsychological assessment. A subset of 26 players also underwent detailed neuroimaging; imaging data in this subset were compared with imaging data acquired in 26 healthy matched controls. MAIN OUTCOME MEASURES Neuropsychological measures, clinical diagnoses of depression, neuroimaging mea-sures of white matter pathology, and a measure of cerebral blood flow. RESULTS Of the 34 former NFL players, 20 were cognitively normal. Four were diagnosed as having a fixed cognitive deficit; 8, mild cognitive impairment; 2, dementia; and 8, depression. Of the subgroup in whom neuroimaging data were acquired, cognitively impaired participants showed the greatest deficits on tests of naming, word finding, and visual/verbal episodic memory. We found significant differences in white matter abnormalities in cognitively impaired and depressed retired players compared with their respective controls. Regional blood flow differences in the cognitively impaired group (left temporal pole, inferior parietal lobule, and superior temporal gyrus) corresponded to regions associated with impaired neurocognitive performance (problems with memory, naming, and word finding). CONCLUSIONS Cognitive deficits and depression appear to be more common in aging former NFL players compared with healthy controls. These deficits are correlated with white matter abnormalities and changes in regional cerebral blood flow.

Patterns of verbal memory performance in mild cognitive impairment, Alzheimer disease, and normal aging.

ObjectiveIndividuals with mild cognitive impairment (MCI) typically demonstrate memory loss that falls between normal aging (NA) and Alzheimer disease (AD), but little is known about the pattern of memory dysfunction in MCI. MethodTo explore this issue, California Verbal Learning Test (CVLT) performance was examined across groups of MCI, AD, and NA. ResultsMCI subjects displayed a pattern of deficits closely resembling that of AD, characterized by reduced learning, rapid forgetting, increased recency recall, elevated intrusion errors, and poor recognition discriminability with increased false-positives. MCI performance was significantly worse than that of controls and better than that of AD patients across memory indices. Although qualitative analysis of CVLT profiles may be useful in individual cases, discriminant function analysis revealed that delayed recall and total learning were the best aspects of learning/memory on the CVLT in differentiating MCI, AD, and NA. ConclusionsThese findings support the position that amnestic MCI represents an early point of decline on the continuum of AD that is different from normal aging.

Dyadic short forms of the Wechsler Adult Intelligence Scale-III.

Various short forms of the Wechsler Adult Intelligence Scale (WAIS)/WAIS-R have been developed to obtain estimates of overall intellectual level, although little research of WAIS-III short forms has been published to date. Full Scale IQ (FSIQ) estimates from four WAIS-III dyadic short forms were obtained by entering selected subtest scores from a mixed neurologic/psychiatric sample (n = 196) into regression equations. Results were cross validated on a second sample (n = 57). Within both samples, WAIS-III FSIQ scores were highly correlated (r = .90-.92, p < .001) with estimated FSIQ scores. Estimated FSIQ fell within 5 points of actual FSIQ in 49% to 74% of cross-validation cases and within 10 points of actual FSIQ in 81% to 93% of the sample. Comparable to findings from previous short-form investigations, actual and estimated FSIQ classification levels agreed in 46% to 67% of cases in the cross-validation sample. These dyadic WAIS-III forms appear appropriate for obtaining gross estimates of FSIQ in similar populations, although caution is recommended in interpreting estimated IQ scores.