Soo Jin Yoon

Hypertensive Pontine Microhemorrhage

Background and Purpose— This study investigated whether the topography of hypertensive pontine microhemorrhages (hPMHs) resembles that of larger primary pontine hemorrhages. Methods— Sixty-nine consecutive patients with small-vessel disease underwent imaging with gradient-echo MRI, and 27 patients with hPMH were detected. Lesion size and location along the rostrocaudal (longitudinal), lateral (coronal), and anteroposterior (sagittal) axes were determined. Results— A total of 52 hPMHs were identified in the 27 patients (mean, 1.93±2.4 per patient). The lesions showed a nonrandom distribution, with a propensity to occur in the middle pons in the rostrocaudal axis, posterior half of the basis pontis in the anteroposterior axis, and central subdivision within the lateral axis. The area of hPMH ranged from 1.3 to 19.0 mm2 (mean, 5.06±3.72 mm2). The size of hPMH did not vary as a function of lesion location. Conclusions— Previous studies reported that primary pontine hemorrhages tend to occur in the middle pons and at the junction of basis pontis and tegmentum. Therefore, topographical correspondences between large and small pontine hemorrhages may provide evidence that the 2 lesions share some etiological basis. Further investigation may determine whether hPMHs portend future symptomatic primary pontine hemorrhages.

Interchanging scores between Clinical Dementia Rating scale and Global Deterioration Scale

&NA; Clinical Dementia Rating (CDR) scale and Global Deterioration Scale (GDS) are commonly used to measure the severity of dementia. However, no specific rules are available to convert the scores of CDR into those of GDS and vice versa. Using a semi‐structured interview, two examiners independently rated CDR and GDS in 78 patients with dementia and 34 controls. Regression analysis showed a curvilinear relationship between CDR and GDS. This curve may provide a rule to interchange the scores of GDS and CDR (or Sum of Boxes of CDR).

Response to rivastigmine transdermal patch or memantine plus rivastigmine patch is affected by apolipoprotein E genotype in Alzheimer patients.

Background/Aims: The apolipoprotein E (APOE) genotype in response to pharmacological treatments in patients with Alzheimer’s disease (AD) remains a matter of controversy. This analysis investigated the effect of the APOE genotype on the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine patch in patients with mild to moderate AD. Methods: Two hundred and six (n = 206) patients with probable AD and Mini-Mental State Examination (MMSE) scores of 10–20 were randomized to rivastigmine patch monotherapy or memantine plus rivastigmine patch for 24 weeks. Of the 206 patients with probable AD, 146 patients who consented to genetic testing for APOE were included and assessed for this subgroup study. Results: There were no significant differences on MMSE, NPI, ADAS-cog, ADCS-ADL, CDR-SB, NPI and FAB between rivastigmine patch monotherapy and memantine plus rivastigmine patch according to the APOE genotype. However, patients with moderately severe AD (MMSE ≤15) who were APOE ε4 carriers showed higher responder rates on ADCS-ADL with memantine plus rivastigmine patch compared to rivastigmine patch monotherapy. Conclusion: Moderately severe AD patients with the APOE ε4 allele may respond more favorably to memantine plus rivastigmine patch than ε4 noncarriers.

Clinical and Neuropsychological Characteristics of a Nationwide Hospital-Based Registry of Frontotemporal Dementia Patients in Korea: A CREDOS-FTD Study

Background: We investigated the demographic, clinical, and neuropsychological characteristics of frontotemporal dementia (FTD) from the Clinical Research Center for Dementia of South Korea (CREDOS)-FTD registry. Methods: A total of 200 consecutive patients with FTD recruited from 16 neurological clinics in Korea were evaluated by cognitive and functional assessments, a screening test for aphasia, behavioral questionnaires, motor assessments, and brain MRI or PET. Results: In our registry, 78 patients were classified as having been diagnosed with behavioral-variant FTD (bvFTD), 70 with semantic dementia (SD), 33 with progressive nonfluent aphasia (PNFA), and 8 with motor neuron disease plus syndrome (MND-plus). The patients with language variants of dementia were older than those with bvFTD. There were no differences in sex ratio, duration of illness, or level of education among the four subgroups. Overall, the patients with bvFTD showed a significantly better performance in cognitive tests. A higher frequency of motor symptoms and a lower frequency of behavioral symptoms were found in PNFA than in bvFTD and SD. The Global Language Index was significantly lower in SD than in bvFTD and PNFA. The MND-plus group had a poorer performance than all the others in all cognitive domains. Conclusion: The neuropsychological, behavioral, motor, and language characteristics of the four subtypes are comparable with those from other series. However, the proportion of SD (37.0%), which was similar to that of bvFTD (41.3%), was higher in our registry than in other series.

Contralesional directional hypermetria associated with line bisection-specific ipsilesional neglect

Patients with contralesional neglect from right hemisphere injuries often fail to be aware of or respond to visual stimuli in the left hemispace. In contrast, other patients with right hemisphere damage rarely demonstrate behavior consistent with task-specific ipsilesional neglect (IN). We performed a series of experiments in a patient with IN on a line bisection task after a right frontal infarct. When asked to perform horizontal limb movements without visual feedback, the patient showed a leftward directional hypermetria. Similar performance was also observed during a representational production of a given distance without sensory input. These results suggest that IN is induced by a directional hypermetria resulting from disruption of the motor-intentional system.

Predictors of Clinical Progression of Subjective Memory Impairment in Elderly Subjects: Data from the Clinical Research Centers for Dementia of South Korea (CREDOS)

Background/Aims: The aims of this study were to determine baseline factors related to the progression of subjective memory impairment (SMI) in elderly subjects and to develop a new modeling scale to predict progression. Methods: Elderly subjects with SMI were recruited from the nationwide Clinical Research Centers for Dementia of South Korea (CREDOS) multicenter cohort and divided into two groups: (1) progressed to mild cognitive impairment or Alzheimers disease or (2) stable without progression. Baseline clinical characteristics were compared between the groups, and the most relevant predictors of progression were assessed. A new modeling scale combining the predictors was developed. Results: In total, 129 subjects with SMI were analyzed. The follow-up duration was 0.5-4.7 years, and the median time to event was 3.64 years. The progressing group (n = 29) differed from the stable group (n = 100) in terms of baseline age, apolipoprotein E4 (APOE4) status, and some cognitive domains. Older age, a lower Mini-Mental State Examination recall score, APOE4 carrier, and a lower verbal delayed recall score were the most relevant predictors of progression, and a new modeling scale with these 4 predictors provided a better explanation of progression. Conclusion: SMI subjects with a higher risk of progression can be identified using a new modeling scale and might need further evaluations and more frequent follow-up.

Prediction Model of Conversion to Dementia Risk in Subjects with Amnestic Mild Cognitive Impairment: A Longitudinal, Multi-Center Clinic-Based Study

BACKGROUND Patients with amnestic mild cognitive impairment (aMCI) have an increased risk of dementia. However, conversion rate varies. Therefore, predicting the dementia conversion in these patients is important. OBJECTIVE We aimed to develop a nomogram to predict dementia conversion in aMCI subjects using neuropsychological profiles. METHODS A total of 338 aMCI patients from two hospital-based cohorts were used in analysis. All patients were classified into 1) verbal, visual, or both, 2) early or late, and 3) single or multiple-domain aMCI according to the modality, severity of memory dysfunction, and multiplicity of involved cognitive domains, respectively. Patients were followed up, and conversion to dementia within 3 years was defined as the primary outcome. Our patients were divided into a training data set and a validation data set. The associations of potential covariates with outcome were tested, and nomogram was constructed by logistic regression model. We also developed another model with APOE data, which included 242 patients. RESULTS In logistic regression models, both modalities compared with visual only (OR 4.44, 95% CI 1.83-10.75, p = 0.001), late compared to early (OR 2.59, 95% CI 1.17-5.72, p = 0.019), and multiple compared to single domain (OR 3.51, 95% CI 1.62-7.60, p = 0.002) aMCI were significantly associated with dementia conversion within 3 years. A nomogram incorporating these clinical variables was constructed on the training data set and validated on the validation data set. Both nomograms with and without APOE data showed good prediction performance (c-statistics ≥ 0.75). CONCLUSIONS This study showed that several neuropsychological profiles of aMCI are significantly associated with imminent dementia conversion, and a nomogram incorporating these clinical subtypes is simple and useful to help to predict disease progression.

Anosognosia and Its Relation to Psychiatric Symptoms in Early-Onset Alzheimer Disease:

Background: We investigated differences in the prevalence of anosognosia and neuropsychiatric symptoms (NPSs) characteristics according to disease severity in patients with early-onset Alzheimer disease (EOAD). Methods: We recruited 616 patients with EOAD. We subdivided participants into 2 groups based on the presence or absence of anosognosia and then again by Clinical Dementia Rating (CDR) scale. We compared the differences in the Neuropsychiatric Inventory (NPI) scores according to anosognosia and disease severity. Results: The percentage of patients with anosognosia in each CDR group steadily increased as the CDR rating increased (CDR 0.5 8.6% vs CDR 1 13.6% vs CDR 2 26.2%). The NPI total score was significantly higher in patients with anosognosia in the CDR 0.5 and 1 groups; by contrast, it had no association in the CDR 2 group. Frontal lobe functions were associated with anosognosia only in the CDR 0.5 and 1 groups. After stratification by CDR, in the CDR 0.5 group, the prevalence of agitation (P = .040) and appetite (P = .013) was significantly higher in patients with anosognosia. In the CDR 1 group, patients with anosognosia had a significantly higher prevalence of delusions (P = .032), hallucinations (P = .048), and sleep disturbances (P = .047). In the CDR 2 group, we found no statistical difference in the frequency of symptoms between patients with and without anosognosia. Conclusion: These results confirm that the prevalence of anosognosia as well as the individual NPS and cognitive functions associated with it differ according to EOAD severity.

Analysis of frontotemporal dementia, amyotrophic lateral sclerosis, and other dementia-related genes in 107 Korean patients with frontotemporal dementia

To identify pathogenic variants in 107 Korean patients with sporadic frontotemporal dementia (FTD), 46 genes related to FTD, amyotrophic lateral sclerosis, and other dementias were screened by next-generation sequencing. Hexanucleotide repeats in C9orf72 gene were also tested by repeat-primed polymerase chain reaction. Next-generation sequencing revealed one known pathogenic variant (c.708+1G>A) in the GRN gene in a patient with behavioral variant FTD (bvFTD). In addition, a novel in-frame deletion (c.2675_2683del) in the CSF1R gene was identified in a patient with bvFTD who had severe bifrontal atrophy with frontal subcortical white matter changes. Novel compound heterozygous variants in the AARS2 gene, c.1040+1G>A and c.636G>A (p.Met212Ile), were found in a patient with bvFTD. Forty-six variants of uncertain significance were detected in other patients. None of the patients had expanded hexanucleotide repeats in C9orf72. These results show that pathogenic variants of known FTD genes are rare in Korean FTD patients but the CSF1R and AARS2 genes should be screened for a genetic diagnosis of FTD or other dementias.

THE RELATIONSHIP BETWEEN COGNITIVE FUNCTION AND FRAILTY

target memory functions. Methods: Nineteen older adults with aMCI (13F; Age: Mean 1⁄4 71.58 years, SD 1⁄4 7.12; Mini-Mental State Examination score: Mean 1⁄4 27.89, SD 1⁄4 1.70; Clinical Dementia Rating score: Mean 1⁄4 0.5) served as participants. They completed two tests that evaluated the use of inherent memory strategies: strategy subscale of the Multifactorial Memory Questionnaire (MMQ; Troyer & Rich, 2002) and a strategic attention task. In addition, all participants completed standardized cognitive assessments including the logical memory subtest of the Wechsler Memory Scale-III (WMS-III; Wechsler, 1997). The strategy subscale of MMQ required participants to score how often they used various memory strategies. The strategic attention task examined participant’s word recall using three different word lists. In each list, words were worth either a high or a low point value, requiring participants to use inherent memory strategies to encode and recall high value words to maximize their score. Correlations were examined between measures of logical memory subtest (immediate and delayed scores) and MMQ strategy subscale (total score), and measures of logical memory subtest (immediate and delayed scores) and strategic attention task (number of high and low value words recalled). Results: Significant positive correlations were found between logical memory delayed score and both total score of the MMQ strategy subscale, r(17) 1⁄4 0.581, p 1⁄4 .009, and number of high value words recalled in list three of the strategic attention task, r(17) 1⁄4 0.515, p 1⁄4 0.024. Conclusions:The findings demonstrate that better use of inherent memory strategies is associated with better memory performance in individuals with aMCI. These findings lend support for the use of strategy-based memory interventions in this population.