Severity Of Global Cognitive Impairment Research Articles

Left and right corticobasal syndrome: comparison of cognitive profiles between metabolic imaging - matched groups

BackgroundCorticobasal syndrome (CBS) is typically asymmetric. Case reports suggest that left-hemisphere CBS (lhCBS) is associated with major language impairment, and right-hemisphere CBS (rhCBS) is associated with major visuospatial deficits, but no group study has ever verified these observations. In our study, we enrolled 49 patients with CBS, classified them as lhCBS or rhCBS based on asymmetry of hypometabolism on brain FDG-PET and compared their cognitive and behavioural profiles.MethodsWe defined asymmetry of hypometabolism upon visual inspection of qualitative PET images and confirmed it through paired comparison of left- and right-hemisphere FDG uptake values. The two groups were also matched for severity of hypometabolism within the more affected and more preserved hemispheres, to unravel differences in the cognitive profiles ascribable specifically to each hemisphere’s functional specializations. All patients were assessed for memory, language, executive and visuospatial deficits, apraxia, neglect, dyscalculia, agraphia and behavioural disturbances.ResultsLhCBS (n. 26) and rhCBS (n. 23) patients did not differ for demographics, disease duration and severity of global cognitive impairment. The two cognitive profiles were largely overlapping, with two exceptions: Digit span forward was poorer in lhCBS, and visual neglect was more frequent in rhCBS.ConclusionsAfter balancing out patients for hemispheric hypometabolism, we did not confirm worse language or visuospatial deficits in, respectively, lhCBS and rhCBS. However, verbal short-term memory was more impaired in lhCBS, and spatial attention was more impaired in rhCBS. Both of these functions reflect the functional specialization of the left and right fronto-parietal pathways, i.e. of the main loci of neurodegeneration in CBS.

Metabolic patterns across core features in dementia with lewy bodies.

To identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern. Brain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core-feature-specific patterns controlling for the main confounding variables (Mini-Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE-sensitive map. Parkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral-frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto-occipital cortex, precuneus, and ventrolateral-frontal metabolism. VH and RBD shared a positive covariance with metabolism in the medial temporal lobe, cerebellum, brainstem, basal ganglia, thalami, and orbitofrontal and sensorimotor cortex. Cognitive fluctuations negatively covaried with occipital metabolism and positively with parietal lobe metabolism. MMSE positively covaried with metabolism in the left superior frontal gyrus, bilateral-parietal cortex, and left precuneus, and negatively with metabolism in the insula, medial frontal gyrus, hippocampus in the left hemisphere, and right cerebellum. Regions of more preserved metabolism are relatively consistent across the variegate DLB spectrum. By contrast, core features were associated with more prominent hypometabolism in specific regions, thus suggesting a close clinical-imaging correlation, reflecting the interplay between topography of neurodegeneration and clinical presentation in DLB patients. Ann Neurol 2019;85:715-725.

Aberrant default mode network in amnestic mild cognitive impairment: a meta-analysis of independent component analysis studies.

Independent component analysis (ICA) is one of the most popular and valid methods to investigate the default mode network (DMN), an intrinsic network which attracts particular attention in amnestic mild cognitive impairment (aMCI). However, previous studies present inconsistent results regarding the topographical organization of the DMN in aMCI. Therefore, we conducted a quantitative, voxel-wise meta-analysis of resting-state ICA studies using Seed-based d Mapping to establish the most consistent pattern of DMN functional connectivity alterations in aMCI. Twenty studies, comprising 23 independent datasets involving 535 patients and 586 healthy controls, met the inclusion criteria. Patients with aMCI exhibited reliably lower DMN functional connectivity than the healthy controls in the bilateral precuneus/posterior cingulate cortices and medial temporal lobes, which are implicated in episodic memory deficits. Moreover, an exploratory meta-regression analysis revealed that greater severity of global cognitive impairment in the patient groups was associated with stronger functional connectivity in the bilateral medial frontal cortices (including the anterior cingulate cortices), left angular gyrus, and right temporal pole extending to the middle temporal gyrus, likely reflecting a compensatory mechanism for maintaining cognitive efficiency. This meta-analysis identifies a consistent pattern of aberrant DMN functional connectivity in aMCI, which facilitates understanding of the neurobiological substrates of this disease.

Constructing a Composite Score for the Seoul Neuropsychological Screening Battery-Core

Background and Purpose The brief version of the Seoul Neuropsychological Screening Battery (SNSB), the SNSB-Core (SNSB-C), has been developed. Although each subtest score of the SNSB-C provides information on different features of broad cognitive functioning or im pairment, a composite score is needed to identify the severity of global cognitive impairment. We aimed to develop and validate a composite score of the SNSB-C that would provide a normative-based summary score of global cognitive functioning, especially for differentiating pa tients with cognitive impairment from normal elderly. Methods A normative sample of 1067 elderly was used to develop a composite score of SNSB-C. The composite score was corrected for the effects of age, years of education, and sex by the regression method. Patients with Alzheimer’s disease ( n=41), vascular dementia (n=40), amnestic mild cognitive impairment (MCI) (n=73), vascular MCI (n=41), and Parkinson’s disease with MCI (n=41) were differentiated from a normal sample (n=70) by the uncorrected and corrected composite scores using receiver operating characteristic (ROC) curve analysis. Results Confirmatory factor analysis showed that the composite score equal weight to each standardized cognitive domain of SNSB-C is appropriate for indexing overall cognitive functioning. The corrected and uncorrected composite scores yielded a satisfactory size of the area under the ROC curve comparable to the Mini Mental State Examination (MMSE). Conclusions The composite scores of SNSB-C, especially the corrected score, provide an index of overall cognitive functioning, and they can be used as an alternative to MMSE for screening patients with cognitive impairment.

Incident Apathy During the First Year After Stroke and Its Effect on Physical and Cognitive Recovery

This prospective study examined the course of cognitive, physical, and social impairment among patients who developed apathy during the first year after stroke. Patients diagnosed with apathy (N = 23) were compared with patients who had no apathy (N = 33) at initial, 3, 6, 9, and 12 months after stroke for severity of global cognitive impairment as measured by Mini-Mental State Examination, severity of impairment in activities of daily living (ADLs) as measured by Functional Independence Measure, and severity of impairment in social functioning as measured by Social Functioning Exam. A total of 41.1% of patients met diagnostic criteria for apathy during the first year after stroke. The mean time from stroke to onset of apathy was 3.8 (3.3 SD) months and the mean duration was 5.6 (2.3 SD) months. Using a linear mixed model, after controlling for age, initial severity of impairment, and major depression, patients in the apathy group had significantly less recovery in cognition (t(149) = -2.06; p = 0.0411) and ADLs (t(104) = -3.37; p = 0.0011) during the first year after stroke compared with nonapathic patients. Apathy is common after stroke and leads to less recovery in cognition and ADLs over the first year after stroke compared with similar nonapathic patients.

Diffuse Tract Damage in the Hemispheric Deep White Matter May Correlate with Global Cognitive Impairment and Callosal Atrophy in Patients with Extensive Leukoaraiosis

Patients with extensive leukoaraiosis are at high risk for vascular dementia. However, these patients exhibit variable severity of global cognitive impairment correlating with callosal atrophy. We hypothesized that callosal atrophy may reflect the severity of HDWM tract damage, which may explain global cognitive impairment. The purpose of this study was to evaluate HDWM tract damage by DTI and to investigate whether HDWM tract damage is associated with callosal atrophy and global cognitive impairment, in patients with extensive leukoaraiosis. Twenty-four consecutive outpatients with extensive leukoaraiosis were enrolled prospectively. The patients underwent cognitive evaluation and 3T MR imaging. The intercorrelation between cognitive score, DA of the HDWM, callosal DA, and callosal volume was analyzed statistically. The correlation of the cognitive score with DA of the HDWM and the corpus callosum was also evaluated by voxel-based analyses by using TBSS. The patients' MMSE scores varied from 10 to 30 (mean, 25.1 ± 6.0). Reduced DA of the HDWM, reduced callosal DA, and callosal atrophy intercorrelated significantly. All of these parameters showed a significant correlation with global cognitive impairment. TBSS analyses showed a significant correlation between MMSE score decline and reduced DA in the diffuse HDWM and the corpus callosum. In patients with extensive leukoaraiosis, atrophy and reduced DA of the corpus callosum may indicate diffuse HDWM tract damage, which may explain global cognitive impairment and development of vascular dementia.

Amyloid imaging of Lewy body‐associated disorders

Clinicopathologic studies of Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) commonly reveal abnormal β-amyloid deposition in addition to diffuse Lewy bodies (α-synuclein aggregates), but the relationship among these neuropathologic features and the development of dementia in these disorders remains uncertain. The purpose of this study was to determine whether amyloid-β deposition detected by PET imaging with Pittsburgh Compound B (PIB) distinguishes clinical subtypes of Lewy body-associated disorders. Nine healthy controls, 8 PD with no cognitive impairment, 9 PD with mild cognitive impairment, 6 DLB, and 15 PDD patients underwent [(11)C]-PIB positron emission tomography imaging, clinical examination, and cognitive testing. The binding potential (BP) of PIB for predefined regions and the mean cortical BP (MCBP) were calculated for each participant. Annual longitudinal follow-up and postmortem examinations were performed on a subset of participants. Regional PIB BPs and the proportion of individuals with abnormally elevated MCBP were not significantly different across participant groups. Elevated PIB binding was associated with worse global cognitive impairment in participants with Lewy body disorders but was not associated with any other clinical or neuropsychological features, including earlier onset or faster rate of progression of cognitive impairment. These results suggest that the presence of fibrillar amyloid-β does not distinguish between clinical subtypes of Lewy body-associated disorders, although larger numbers are needed to more definitively rule out this association. Amyloid-β may modify the severity of global cognitive impairment in individuals with Lewy body-associated dementia.

Neuropsychological Predictors of Rapidly Progressing Patients with Alzheimer’s Disease

Background: Alzheimer disease (AD) has heterogeneous clinical manifestations. Different neuropsychological profiles in AD patients might be indicative of the diffusion of the pathological process and might be associated with differences in rates of disease progression. Methods: We studied 154 newly diagnosed AD patients (65.6% women; mean age: 73 years). Performance in memory, executive functions, praxis and language domains was categorized into mild, moderate and severe impairment. The time-dependent probability of losing 5 points on the Mini-Mental State Examination (MMSE) over 2 years was considered as disease progression and evaluated by survival analysis. Results: One fourth of the patients decreased by ≧5 MMSE points over the 2-year follow-up. Rapid disease progression was more frequent in more educated patients and in those with moderate severity of global cognitive impairment. In univariate analysis, more severe memory and executive functioning impairment were associated with higher probabilities of progression. The association with memory was explained by differences in executive function impairment that remained statistically significant in multivariate analyses. Conclusions: Patients with more severe executive functioning impairment have a worse prognosis over 2 years. This might be due to involvement of the prefrontal cortex by the pathological process of AD in patients with severe executive deficits.

Visuospatial Dysfunction May Be a Key in the Differentiation between Alzheimer’s Disease and Subcortical Cognitive Impairment in Moderate to Severe Stages

Aims: Recent studies have suggested that subcortical cognitive impairment (SubCI) and Alzheimer’s disease (AD) can be differentiated by visuospatial tasks. We addressed at what severity stage these differences become apparent and what components in visuospatial processes are subject to impairment. Methods: Sixty patients with AD, 22 with vascular cognitive impairment and 63 with extrapyramidal diseases with cognitive impairment were assessed using the revised Hasegawa Dementia Scale (HDSR), clock drawing/reading/matching tests (CDT, CRT, CMT), figure copying (FIG) and Frontal Assessment Battery (FAB). Patients were categorized according to the HDSR scores in order to control for the severity of global cognitive impairment. Raw scores were converted to Z-scores for comparisons. Results: In the mild stage, results of all measures were comparable between AD and SubCI. In the moderate-severe stage, scores of CDT, CRT, CMT, FIG and FAB were significantly lower in SubCI. The results suggest that (given that global cognition is controlled for) visuo-perception, visuo-construction and semantic-numerical analyses of visual information may be more impaired in SubCI than AD. Conclusions: AD and SubCI may be difficult to be differentiated in the mild stages, and the visuospatial cognitive system may be extensively defective in SubCI.

P4-175: A comparison of Pentagon copying and three clock scoring methods among illiterate or low educated elderly Korean

Illiteracy or low education is prevalent among current elderly Korean. Although dementia screening tests are available, they have not gained widespread use in community or primary care settings in Korea. This study compared the dementia screening performance of Pentagon copying and three clock drawing test (CDT) scoring systems for elderly Korean. We reviewed the charts of consecutive subjects referred between 2004 and 2005 to the geriatric health clinic and research institute (GHCRI). Subjects included were 30 Alzheimer's disease (AD) subjects and 60 normal subjects. All subjects had all undergone the CERAD–K as well as an MMSE–K, pentagon copy (scored by Bourke method and MMSE method) and CDT (scored by 3 methods: the Sunderland method, the Rouleau method, and the Watson method). AD subjects with low education were found to copy significantly worse pentagons than those with high education or normal subjects. Copying scores and CDT scores significantly correlated with MMSE scores for the AD and normal groups. Using the CERAD–K as the good standard, the sensitivity and specificity of the pentagon copying scores and the Watson method of scoring CDT to predict an abnormal CERAD–K score were 65% and 72%, 60% and 71%, respectively. Deterioration in pentagon copying and CDT correlates with severity of global cognitive impairment in low educated elderly Koreans. This study suggests that in the socio–cultural context for Korean, pentagon copy as well as CDT are feasible for use in a clinical setting for dementia screening.

P2-113: The utility of the clock drawing test for cognitive impairment screening

Because of improved symptomatic treatment options for dementia, early detection is an important issue. Therefore, a simple and quickly administered test at low cost is needed. The clock drawing test (CDT) provides a simple and reliable measure of a comprehensive range of cognitive functions. To examine the usefulness of the CDT when used as a cognitive screening instrument for dementia, and to compare different scoring methods of CDT, and to check the correlations with the Mini–Mental State Examination (MMSE) score and Hasegawa Dementia Scale (HDS). We reviewed the charts of the 37 patients with memory complaints, visiting the outpatient clinic between January 2005 and July 2005, of which 20 patients were diagnosed with the Alzheimer's dementia, 10 with vascular dementia, and 7 with mild cognitive impairment. The patients had all undergone the Korean version of the MMSE and the Korean version of revised form of HDS. For the CDT, each patient was given a blank paper and asked to draw a clock face with all numbers on it and then draw hands on the clock to make it read 2:40. The CDT was scored by 5 different scoring methods (Sunderland, modified Shulman, Rouleau, Cahn, simplified Freedman's methods). The patients were 25 women and 12 men; their mean age was 73.59 years (±6.94) (range 56 – 92). The mean MMSE score was 19.54±4.45, and the mean HDS score was 17.22±5.36. The MMSE score was significantly correlated with all methods of scoring the CDT (r= 0.672∼0.728, p <0.01), the Sunderland scoring method producing the highest correlation. Similarly, all five scoring methods correlated significantly with the HDS score (r= 0.406∼0.494), less than the MMSE score. All correlations between CDT scoring methods were statistically significant (r= 0.93∼0.98, p<0.01). Deterioration in the CDT score correlates with severity of global cognitive impairment, as assessed by the MMSE and HDS. Therefore the CDT can be used as useful cognitive impairment screening, either by itself or as a part of a brief neuropsychological test battery.

Frontal Lobe Hypometabolism and Impaired Insight in Alzheimer Disease

The authors examined the relationship between impaired insight regarding cognitive and functional deficits and frontal cortex hypometabolism in 41 patients with Alzheimer disease (AD). Regional cerebral glucose metabolism was determined with (18F)fluorodeoxyglucose and positron emission tomography. Level of insight was measured with the clinician-rated Neurobehavioral Rating Scale, and severity of global cognitive impairment was determined with the Mini-Mental State Exam. Inaccurate insight was correlated with glucose metabolic rate in the right lateral frontal cortex (Brodmann areas 6 and 45, and the lateral aspect of Brodmann areas 8 and 9) after controlling for global cognitive dysfunction. The findings from this study help to further elucidate the neurobiological mechanisms underlying impaired insight in AD, indicating a link between this important clinical phenomenon and dysmetabolism in a focal region of the right prefrontal cortex.

Frontal Lobe Hypometabolism and Impaired Insight in Alzheimer Disease

The authors examined the relationship between impaired insight regarding cognitive and functional deficits and frontal cortex hypometabolism in 41 patients with Alzheimer disease (AD).Regional cerebral glucose metabolism was determined with (18F)fluorodeoxyglucose and positron emission tomography. Level of insight was measured with the clinician-rated Neurobehavioral Rating Scale, and severity of global cognitive impairment was determined with the Mini-Mental State Exam.Inaccurate insight was correlated with glucose metabolic rate in the right lateral frontal cortex (Brodmann areas 6 and 45, and the lateral aspect of Brodmann areas 8 and 9) after controlling for global cognitive dysfunction.The findings from this study help to further elucidate the neurobiological mechanisms underlying impaired insight in AD, indicating a link between this important clinical phenomenon and dysmetabolism in a focal region of the right prefrontal cortex.

Global cognitive impairment should be taken into account in SPECT–neuropsychology correlations: the example of verbal memory in very mild Alzheimer’s disease

To examine the impact of severity of global cognitive impairment on SPECT-neuropsychology correlations, we correlated a verbal memory test with brain perfusion in patients with very mild Alzheimer's disease (AD), taking into account the Mini-Mental State Examination (MMSE) score as an index of global cognitive impairment. Twenty-nine outpatients (mean age 78.2+/-5.5 years) affected by very mild, probable AD underwent brain SPECT with 99mTc-ethylcysteinate dimer and a word list learning test. SPM99 was used for voxel-based correlation analysis after normalisation to mean cerebellar counts (height threshold: p<0.01). In a first analysis, only age and years of education were inserted as nuisance covariates, while in a second analysis the MMSE score was inserted as well. In the first analysis, two clusters of significant correlation were found in both hemispheres, mainly including regions of the right hemisphere, such as the inferior parietal lobule, the middle temporal gyrus and the posterior cingulate. Significant correlation in the left hemisphere was observed in the lingual lobule, the parietal precuneus and the posterior cingulate. After taking into consideration the MMSE, the largest cluster of correlation was found in the left hemisphere, including the parietal gyrus angularis, the posterior cingulate and the middle temporal gyrus. The wide differences observed between the correlations achieved with and without taking into account the MMSE score indicate that severity of global cognitive impairment should be considered when searching for brain perfusion-neuropsychology correlations. In the present case, this strategy resulted in correlations that more closely matched neuropsychological models of verbal memory deficit.

Awareness of financial skills in dementia

The present study examined the relations among levels of cognitive functioning, executive dysfunction, and awareness of financial management capabilities among a sample of 42 community-dwelling persons with dementia. Financial tasks on the Measure of Awareness of Financial Skills (MAFS) were dichotomized as simple or complex based on Piaget's operational levels of childhood cognitive development. Severity of global cognitive impairment and executive dysfunction were significantly related to awareness of financial abilities as measured by informant-participant discrepancy scores on the MAFS. For persons with mild and moderate/severe dementia, and persons with and without executive dysfunction, proportions of awareness within simple and complex financial task categories were tabulated. Significantly less awareness of financial abilities occurred on complex compared with simple tasks. Individuals with mild dementia were significantly less aware of abilities on complex items, whereas persons with moderate/severe dementia were less aware of abilities, regardless of task complexity. Similar patterns of awareness were observed for individuals with and without executive dysfunction. These findings support literature suggesting that deficits associated with dementia first occur for complex cognitive tasks involving inductive reasoning or decision-making in novel situations, and identify where loss of function in the financial domain may first be expected.

Ischemic white matter damage and cognitive impairment

AbstractWhite matter damage may play an important role in the pathogenesis of vascular dementia. White matter abnormalities are easily visualized as white matter high‐intensity lesions (WML) on T2‐weighted magnetic resonance images. The extent of WML may be an indicator of cognitive impairment, in particular, impairment related to frontal lobe dysfunction. However, it is unclear whether the extent of WML is an independent predictor of cognitive impairment. In patients with extensive WML, atrophy of the corpus callosum may be an important predictor of global cognitive impairment. We investigated the relationship between the extent of WML and callosal size with cognitive function in patients who had been diagnosed with lacunar stroke or no specific neurological disease. Multivariate analysis showed that only callosal size and age were significant independent predictors of mini‐mental state examination scores (a measure of global cognitive function), whereas only the extent of WML was an independent predictor of the score on the verbal fluency task (a measure of frontal lobe function). Callosal atrophy may be an important predictor of global cognitive impairment in patients with WML, whereas the extent of WML per se may be related to impairment of frontal lobe function independent of callosal atrophy. White matter high‐intensity lesions with callosal atrophy may indicate a severe form of white matter damage with axonal loss, the degree of which may determine the severity of global cognitive impairment. Our longitudinal study revealed an association between progression of WML and vascular risk factor status during follow up in patients with initially mild WML. Early detection of WML without callosal atrophy at a stage of subtle cognitive impairment and slowing the progression of WML to a severe form with callosal atrophy might prevent the development of dementia.