Longitudinal amyloid cognitive composite in preclinical Alzheimer's disease.

BACKGROUND AND PURPOSE: Previous studies have developed several cognitive composites in preclinical Alzheimer disease (AD). However, more sensitive measures to track cognitive changes and therapeutic efficacy in preclinical AD are needed considering the diverse sociocultural and linguistic backgrounds. This study developed a composite score that can sensitively detect the amyloid-ß (Aß)-related cognitive trajectory of preclinical AD using Korean data. METHODS: A total of 196 cognitively normal participants who underwent amyloid positron emission tomography were followed-up with neuropsychological assessments. We developed the Longitudinal Amyloid Cognitive Composite in Preclinical AD (LACPA) using the linear mixed-effects model (LMM) and z scores. The LMM was also used to investigate the longitudinal sensitivity of the LACPA and the association between time-varying brain atrophy and the LACPA. RESULTS: Considering the group-time interaction effects of each subtest, the Seoul Verbal Learning Test-Elderly version immediate recall/delayed recall/recognition, the Korean Trail Making Test B Time, and the Korean Mini-Mental State Examination were selected as components of the LACPA. The LACPA exhibited a significant group-time interaction effect between the Aß+ and Aß- groups (t = -3.288, p = 0.001). Associations between time-varying LACPA and brain atrophy were found in the bilateral medial temporal, right lateral parietal, and right lateral frontal regions, and hippocampal volume. CONCLUSIONS: The LACPA may contribute to reduction in time and financial burden when monitoring Aß-related cognitive decline and therapeutic efficacy of the disease-modifying agents specifically targeting Aß in secondary prevention trials.

A Comprehensive Evaluation of the Process of Copying a Complex Figure in Early- and Late-Onset Alzheimer Disease: A Quantitative Analysis of Digital Pen Data.

BACKGROUND: The Rey-Osterrieth Complex Figure Test (RCFT) is a neuropsychological test that is widely used to assess visual memory and visuoconstructional deficits in patients with cognitive impairment, including Alzheimer disease (AD). Patients with AD have an increased tendency for exhibiting extraordinary behaviors in the RCFT for selecting the drawing area, organizing the figure, and deciding the order of images, among other activities. However, the conventional scoring system based on pen and paper has a limited ability to reflect these detailed behaviors. OBJECTIVE: This study aims to establish a scoring system that addresses not only the spatial arrangement of the finished drawing but also the drawing process of patients with AD by using digital pen data. METHODS: A digital pen and tablet were used to copy complex figures. The stroke patterns and kinetics of normal controls (NCs) and patients with early-onset AD (EOAD) and late-onset AD (LOAD) were analyzed by comparing the pen tip trajectory, spatial arrangement, and similarity of the finished drawings. RESULTS: Patients with AD copied the figure in a more fragmented way with a longer pause than NCs (EOAD: P=.045; LOAD: P=.01). Patients with AD showed an increased tendency to draw the figures closer toward the target image in comparison with the NCs (EOAD: P=.005; LOAD: P=.01) Patients with AD showed the lower accuracy than NCs (EOAD: P=.004; LOAD: P=.002). Patients with EOAD and LOAD showed similar but slightly different drawing behaviors, especially in space use and in the initial stage of drawing. CONCLUSIONS: The digitalized complex figure test evaluated copying performance quantitatively and further elucidated the patients' ongoing process during copying. We believe that this novel approach can be used as a digital biomarker of AD. In addition, the repeatability of the test will delineate the process of executive functions and constructional organization abilities with disease progression.

A Validation Study of the Inbrain CST: a Tablet Computer-based Cognitive Screening Test for Elderly People with Cognitive Impairment.

BACKGROUND: Computerized versions of cognitive screening test could have advantages over pencil-and-paper versions by eliminating rater-dependent factors and saving the time required to score the tests and report the results. We developed a computerized cognitive screening test (Inbrain Cognitive Screening Test [Inbrain CST]) that takes about 30 minutes to administer on a touchscreen computer and is composed of neuropsychological tests already shown to be sensitive in detecting early cognitive decline in Alzheimer's disease (AD). The aims of this study were to 1) introduce normative data for Inbrain CST, 2) verify its reliability and validity, 3) assess clinical usefulness, and 4) identify neuroanatomical correlates of Inbrain CST. METHODS: The Inbrain CST runs on the Microsoft Windows 10 operating system and comprises 7 subtests that encompass 5 cognitive domains: attention, language, visuospatial, memory, and executive functions. First, we recruited 480 cognitively normal elderly people (age 50-90) from communities nationwide to establish normative data for Inbrain CST. Second, we enrolled 97 patients from our dementia clinic (26 with subjective cognitive decline [SCD], 42 with amnestic mild cognitive impairment [aMCI], and 29 with dementia due to AD) and investigated sensitivity and specificity of Inbrain CST for discriminating cognitively impaired patients from those with SCD using receiver operating characteristic (ROC) curve analyses. Third, we compared the Inbrain CST scores with those from another neuropsychological test battery to obtain concurrent validity and assessed test-retest reliability. Finally, magnetic resonance imaging (MRI)-based cortical thickness analyses were performed to provide anatomical substrates for performances on the Inbrain CST. RESULTS: First, in the normative sample, the total score on the Inbrain CST was significantly affected by age, years of education, and gender. Second, Inbrain CST scores among the three patient groups decreased in the order of SCD, aMCI, and AD dementia, and the ROC curve analysis revealed that Inbrain CST had good discriminative power for differentiating cognitively impaired patients from those with SCD. Third, the Inbrain CST subtests had high concurrent validity and test-retest reliability. Finally, in the cortical thickness analysis, each cognitive domain score and the total score of Inbrain CST showed distinct patterns of anatomical correlates that fit into the previously known brain-behavior relationship. CONCLUSION: Inbrain CST had good validity, reliability, and clinical usefulness in detecting cognitive impairment in the elderly. Furthermore, it showed neuroanatomical validity through MRI cortical thinning patterns. These results suggest that Inbrain CST is a useful cognitive screening tool with efficiency and validity to detect mild impairments in cognition in clinical settings.

Relative impact of amyloid-ß, lacunes, and downstream imaging markers on cognitive trajectories.

SEE COHEN DOI101093/AWW183 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Amyloid-ß and cerebral small vessel disease are the two major causes of cognitive impairment in the elderly. However, the underlying mechanisms responsible for precisely how amyloid-ß and cerebral small vessel disease affect cognitive impairment remain unclear. We investigated the effects of amyloid-ß and lacunes on downstream imaging markers including structural network and cortical thickness, further analysing their relative impact on cognitive trajectories. We prospectively recruited a pool of 117 mild cognitive impairment patients (45 amnestic type and 72 subcortical vascular type), from which 83 patients received annual follow-up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and 87 patients received a second Pittsburgh compound B positron emission tomography analysis. Structural networks based on diffusion tensor imaging and cortical thickness were analysed. We used linear mixed effect regression models to evaluate the effects of imaging markers on cognitive decline. Time-varying Pittsburgh compound B uptake was associated with temporoparietal thinning, which correlated with memory decline (verbal memory test, unstandardized ß = -0.79, P < 0.001; visual memory test, unstandardized ß = -2.84, P = 0.009). Time-varying lacune number was associated with the degree of frontoparietal network disruption or thinning, which further affected frontal-executive function decline (Digit span backward test, unstandardized ß = -0.05, P = 0.002; Stroop colour test, unstandardized ß = -0.94, P = 0.008). Of the multiple imaging markers analysed, Pittsburgh compound B uptake and the number of lacunes had the greatest association with memory decline and frontal-executive function decline, respectively: Time-varying Pittsburgh compound B uptake (standardized ß = -0.25, P = 0.010) showed the strongest effect on visual memory test, followed by time-varying temporoparietal thickness (standardized ß = 0.21, P = 0.010) and time-varying nodal efficiency (standardized ß = 0.17, P = 0.024). Time-varying lacune number (standardized ß = -0.25, P = 0.014) showed the strongest effect on time-varying digit span backward test followed by time-varying nodal efficiency (standardized ß = 0.17, P = 0.021). Finally, time-varying lacune number (ß = -0.22, P = 0.034) showed the strongest effect on time-varying Stroop colour test followed by time-varying frontal thickness (standardized ß = 0.19, P = 0.026). Our multimodal imaging analyses suggest that cognitive trajectories related to amyloid-ß and lacunes have distinct paths, and that amyloid-ß or lacunes have greatest impact on cognitive decline. Our results provide rationale for the targeting of amyloid-ß and lacunes in therapeutic strategies aimed at ameliorating cognitive decline.

Callosal Motor Impersistence: A Novel Disconnection Syndrome.

Motor impersistence, an inability to sustain a certain position or movement, is a motor-intentional disorder, caused more often by right than left hemisphere lesions. Since the right hemisphere is dominant for mediating motor persistence, callosal lesions that disconnect the left hemisphere from the right may induce impersistence of the right upper and lower limbs. After an undiagnosed left callosal infarction, a 65-year-old right-handed man suddenly developed a transient loss of volitional movement of his left leg. Five days after onset, he was admitted to our hospital with signs of callosal disconnection: left-hand agraphia and apraxia, left-hand tactile anomia, failures on cross-replication of hand postures, and intermanual conflict. He had neither weakness nor ataxia of his upper or lower extremities, but when asked to keep his arms or legs extended he could not maintain his right arm and leg in the extended position, suggesting motor impersistence in his dominant limbs. When we examined him 3 months after onset, the motor impersistence had disappeared. In conclusion, motor impersistence of dominant limbs can result from isolated callosal injury that disconnects the left hemisphere from the right hemisphere's frontal-subcortical networks.

Neuroanatomical Correlates of Hypophonia in Subcortical Vascular Cognitive Impairment.

BACKGROUND/AIMS: Early detection and intervention may alter the disease course of subcortical vascular cognitive impairment (SVCI). Patients with SVCI have white matter ischemia that disrupts connections between the cortex and subcortical gray matter and therefore manifest various symptoms such as motor disturbances and behavioral/cognitive dysfunction. Reduced vocal loudness, or hypophonia, is one of the common motor symptoms of SVCI, but few studies have systematically investigated it in this patient population. The main purpose of this investigation was to identify neural pathways underlying hypophonia in patients with SVCI. METHODS: Eighty-eight patients with SVCI and 21 normal controls performed phonation tasks. Diffusion tensor imaging data from 73 patients were utilized to measure white matter changes associated with hypophonia. RESULTS: Correlational analyses between white matter fractional anisotropy values and the decibel level of the "sustained phonation" task identified the left midbrain cerebral peduncle (corticobulbar tract), external capsule, corona radiata/internal capsule, and bilateral frontal white matter as possible neural correlates for hypophonia. CONCLUSION: Our results support the notion that hypophonia in SVCI patients might be caused by the impairment of the pyramidal and extrapyramidal systems. This study provides a unique contribution towards understanding the neuropathology of hypophonic features in this population.

Group- and Home-Based Cognitive Intervention for Patients with Mild Cognitive Impairment: A Randomized Controlled Trial.

BACKGROUND: We examined the efficacy of group-based cognitive intervention (GCI) and home-based cognitive intervention (HCI) in amnestic mild cognitive impairment (aMCI) and intervention effects on serum brain-derived neurotrophic factor (BDNF). METHODS: In this randomized and rater-blinded trial, 293 patients with aMCI from 18 nationwide hospitals were randomized: 96 to the GCI group, 98 to the HCI group and 99 to the control group. For 12 weeks, subjects receiving GCI participated twice per week in group sessions led by trained instructors, and those receiving HCI completed homework materials 5 days per week. They were assessed at baseline, postintervention (PI) and at the 6-month follow-up after the intervention. The primary endpoint was the change from baseline to PI in the modified Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog). RESULTS: In comparison to the controls (a 0.8-point decrease), the subjects receiving GCI (a 2.3-point decrease, p = 0.01) or HCI (a 2.5-point decrease, p = 0.02) showed significant improvements in the modified ADAS-Cog at PI, respectively. By the 6-month follow-up, those receiving GCI or HCI had better scores in the modified ADAS-Cog than the controls. The changes in BDNF levels significantly correlated with the changes in the modified ADAS-Cog in the GCI (r = -0.29, p = 0.02 at PI) and HCI (r = -0.27, p = 0.03 at 6-month follow-up) groups, respectively. CONCLUSIONS: The GCI and HCI resulted in cognitive improvements in aMCI. An enhanced brain plasticity may be a component of the mechanism underpinning the cognitive improvements associated with the cognitive interventions.

Survival in Subcortical Vascular Dementia: Predictors and Comparison to Probable Alzheimer's Disease in a Tertiary Memory Clinic Population.

BACKGROUND: Subcortical vascular dementia (SVaD) is one of the most common dementias, after Alzheimer's disease (AD) dementia. Few survival analyses in SVaD patients have been reported. METHODS: The dates and causes of death of 146 SVaD and 725 AD patients were included. We used the Cox proportional hazards model to compare survival between SVaD and AD patients and to explore possible factors related to survival of SVaD patients. RESULTS: The median survival time after the onset of SVaD (109 months) was shorter than that recorded for AD (152 months). The most common cause of death in SVaD was stroke (47.1%). Factors associated with shorter survival in SVaD were late onset, male sex, worse baseline cognition, absence of hypertension and a family history of stroke. CONCLUSIONS: Stroke prevention may be important in SVaD treatment because 47.1% of SVaD patients died of stroke. A family history of stroke and absence of hypertension were associated with a shorter survival in SVaD, suggesting the existence of genetic or unknown risk factors.

Postmorbid learning of saxophone playing in a patient with frontotemporal dementia.

Some patients with frontotemporal dementia (FTD) show an artistic enhancement of musical abilities. However, no patients with FTD, to date, have been reported to be able to learn how to play a musical instrument after disease onset. Herein we describe a patient (J. K.) who had never played any musical instruments premorbidly, but who learned to play the saxophone after being diagnosed with a behavioral variant of FTD. He mastered a repertoire that consisted of 10 pieces of Korean folk songs over a period of three years. Furthermore, his saxophone skills were high enough to outperform other students in his class.

Cognitive and Motor Aspects of Parkinson's Disease Associated with Dysphagia.

BACKGROUND: Dysphagia is a common symptom and an important prognostic factor in Parkinson's disease (PD). Although cognitive and motor dysfunctions may contribute to dysphagia in patients with PD, any specific association between such problems and swallowing functions is unclear. Here, we examined the potential relationship between cognitive/motor components and swallowing functions in PD. We evaluated the contributions of cognition and motor function to the components of swallowing via video fluoroscopic swallowing (VFS) experiments. METHODS: We prospectively enrolled 56 patients without dementia having PD. Parkinson's disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). All participants received neuropsychological tests covering general mental status, visuospatial function, attention, language, learning and memory, and frontal executive function. The well-validated "modified barium swallow impairment profile" scoring system was applied during VFS studies to quantify swallowing impairments. Finally, correlations between neuropsychological or motor functions and impairment in swallowing components were calculated. RESULTS: The most significant correlations were found between the frontal/executive or learning/memory domains and the oral phase of swallowing, though a minor component of the pharyngeal phase correlated with frontal function as well. Bradykinesia and the UPDRS total score were associated with both the pharyngeal and oral phases. CONCLUSIONS: Our findings suggest that cognitive dysfunctions are associated with the oral phase of swallowing in patients with early stage PD while the severity of motor symptoms may be associated with overall swallowing function.

Higher education affects accelerated cortical thinning in Alzheimer's disease: a 5-year preliminary longitudinal study.

BACKGROUND: Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD). METHODS: We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (≤9 years). RESULTS: As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD. CONCLUSION: Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.

Amyloid burden, cerebrovascular disease, brain atrophy, and cognition in cognitively impaired patients.

BACKGROUND: We investigated the independent effects of Alzheimer's disease (AD) and cerebrovascular disease (CVD) pathologies on brain structural changes and cognition. METHODS: Amyloid burden (Pittsburgh compound B [PiB] retention ratio), CVD markers (volume of white matter hyperintensities [WMH] and number of lacunae), and structural changes (cortical thickness and hippocampal shape) were measured in 251 cognitively impaired patients. Path analyses were utilized to assess the effects of these markers on cognition. RESULTS: PiB retention ratio was associated with hippocampal atrophy, which was associated with memory impairment. WMH were associated with frontal thinning, which was associated with executive and memory dysfunctions. PiB retention ratio and lacunae were also associated with memory and executive dysfunction without the mediation of hippocampal or frontal atrophy. CONCLUSIONS: Our results suggest that the impacts of AD and CVD pathologies on cognition are mediated by specific brain regions.

Are depressive symptomatology and self-focused attention associated with subjective memory impairment in older adults?

BACKGROUND: Subjective memory impairment (SMI) refers to conditions in which people complain of memory problems despite intact cognition. The primary purpose of the present study was to examine the roles of self-focused attention and depressive symptomatology in subjective memory complaints. METHODS: One hundred and eight patients who visited a memory disorder clinic with complaints of memory decline, but who were found on subsequent neuropsychological assessment to have normal cognitive function, were recruited to participate in the study. The severity of subjective memory complaints was measured with the modified Multifactorial Memory Questionnaire. In addition, neuropsychological functions, self-focused attention, and depressive symptomatology were also assessed. RESULTS: The results showed that the severity of SMI was not significantly correlated with any of the neuropsychological test scores except for the complex figure copy. The severity of SMI, however, was significantly correlated with self-focused attention and depressive symptomatology. Hierarchical regression analysis revealed that self-focused attention and depressive symptomatology significantly contributed to the severity of subjective memory complaints over and above the neuropsychological test performance. The interaction effects between self-focused attention/depressive symptomatology and objective memory performance on the severity of SMI were not significant. CONCLUSIONS: In conclusion, self-focused attention and depressive symptomatology appear to play important roles in the severity of SMI, even though it is not clear how these factors interact with objective memory performance. Clinical implications as well as limitations of the present study were discussed.

The Usefulness of 18F-FDG PET to Differentiate Subtypes of Dementia: The Systematic Review and Meta-Analysis.

Background and Purpose: Dementia subtypes, including Alzheimer's dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) in differentiating these subtypes for precise treatment and management. Methods: A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the gold-standard clinical diagnosis for dementia subtypes. Results: From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88-0.98) and specificity was 0.84 (95% CI, 0.70-0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70-0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80-0.91) and the specificity was 0.88 (95% CI, 0.80-0.91). The studies mostly used case-control designs with visual and quantitative assessments. Conclusions: 18F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.

Survival of Alzheimer's disease patients in Korea.

BACKGROUND/AIMS: The natural history of Alzheimer's disease (AD) has rarely been studied in the Korean population. Our study on survival analyses in Korean AD patients potentially provides a basis for cross-cultural comparisons. METHODS: We studied 724 consecutive patients from a memory disorder clinic in a tertiary hospital in Seoul, who were diagnosed as having AD between April 1995 and December 2005. Deaths were identified by the Statistics Korea database. The Kaplan-Meier method was used for survival analysis, and a Cox proportional hazard model was used to assess factors related to patient survival. RESULTS: The overall median survival from the onset of first symptoms and from the time of diagnosis was 12.6 years (95% confidence interval 11.7-13.4) and 9.3 years (95% confidence interval 8.7-9.9), respectively. The age of onset, male gender, history of diabetes mellitus, lower Mini-Mental State Examination score, and higher Clinical Dementia Rating score were negatively associated with survival. There was a reversal of risk of AD between early-onset and later-onset AD, 9.1 years after onset. CONCLUSIONS: The results of our study show a different pattern of survival compared to those studies carried out with western AD populations. Mortality risk of early-onset AD varied depending on the duration of follow-up.

Classification and prediction of cognitive trajectories of cognitively unimpaired individuals.

Objectives: Efforts to prevent Alzheimer's disease (AD) would benefit from identifying cognitively unimpaired (CU) individuals who are liable to progress to cognitive impairment. Therefore, we aimed to develop a model to predict cognitive decline among CU individuals in two independent cohorts. Methods: A total of 407 CU individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and 285 CU individuals from the Samsung Medical Center (SMC) were recruited in this study. We assessed cognitive outcomes by using neuropsychological composite scores in the ADNI and SMC cohorts. We performed latent growth mixture modeling and developed the predictive model. Results: Growth mixture modeling identified 13.8 and 13.0% of CU individuals in the ADNI and SMC cohorts, respectively, as the "declining group." In the ADNI cohort, multivariable logistic regression modeling showed that increased amyloid-ß (Aß) uptake (ß [SE]: 4.852 [0.862], p < 0.001), low baseline cognitive composite scores (ß [SE]: -0.274 [0.070], p < 0.001), and reduced hippocampal volume (ß [SE]: -0.952 [0.302], p = 0.002) were predictive of cognitive decline. In the SMC cohort, increased Aß uptake (ß [SE]: 2.007 [0.549], p < 0.001) and low baseline cognitive composite scores (ß [SE]: -4.464 [0.758], p < 0.001) predicted cognitive decline. Finally, predictive models of cognitive decline showed good to excellent discrimination and calibration capabilities (C-statistic = 0.85 for the ADNI model and 0.94 for the SMC model). Conclusion: Our study provides novel insights into the cognitive trajectories of CU individuals. Furthermore, the predictive model can facilitate the classification of CU individuals in future primary prevention trials.

Development and preliminary validation of a virtual reality memory test for assessing visuospatial memory.

Background: Visuospatial memory impairment is a common symptom of Alzheimer's disease; however, conventional visuospatial memory tests are insufficient to fully reflect visuospatial memory impairment in daily life. Methods: To address patients' difficulties in locating and recalling misplaced objects, we introduced a novel visuospatial memory test, the Hidden Objects Test (HOT), conducted in a virtual environment. We categorized HOT scores into prospective memory, item free-recall, place free-recall, item recognition, and place-item matching scores. To validate the VR memory test, we compared HOT scores among individuals with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), and normal controls (NC), and also compared these scores with those of conventional neuropsychological tests. We tracked the participants' movement paths in the virtual environment and assessed basic features, such as total distance, duration, and speed. Additionally, we performed walking trajectory pattern mining such as outlier and stay-point detection. Results: We designed and implemented the HOT to simulate a house's living room and assess participants' ability to locate hidden objects. Our preliminary results showed that the total HOT score differed among 17 patients with AD, 14 with aMCI, and 15 NC (p < 0.001). The total HOT score correlated positively with conventional memory test scores (p < 0.001). Walking trajectories showed that patients with AD and aMCI wandered rather than going straight to the hidden objects. In terms of basic features, the total duration was significantly greater in AD than in NC (p = 0.008). In terms of trajectory pattern mining, the number of outliers, which were over 95% of the estimated trajectory, was significantly higher in AD than in NC (p = 0.002). The number of stay points, an index in which participants stayed in the same position for more than 2 s, was significantly higher in patients with AD and aMCI compared with NC (AD vs. NC: p = 0.003, aMCI vs. NC: p = 0.019). Conclusion: The HOT simulating real life showed potential as an ecologically valid test for assessing visuospatial memory function in daily life. Walking trajectory analysis suggested that patients with AD and aMCI wandered rather than going straight toward the hidden objects.

Efficacy of smartphone application-based multi-domain cognitive training in older adults without dementia.

Background: As the population ages and the prevalence of dementia increases, there is a growing emphasis on the importance of cognitive training to prevent dementia. A smartphone application-based cognitive training software program, BeauBrain Trainer (BBT), has been developed to provide better access to cognitive training for older adults. Numerous studies have revealed the effectiveness of cognitive training using a cognitive assessment tool. However, relatively few studies have evaluated brain activation using brain imaging as a result of improved cognitive function. Methods: All participants were required to download the BBT, an Android-based application for cognitive training, onto their own smartphone or tablet computer and to engage in cognitive training at home. Older adults without dementia were enrolled in this study, including 51 participants in the intervention group and 50 participants in the control group. The BBT comprised a set of 12 cognitive tasks, including two tasks in each of the following six cognitive domains: attention, language, calculation, visuospatial function, memory, and frontal/executive function. Each cognitive task was divided into four blocks based on its level of difficulty. A 16-week cognitive training was designed to carry out cognitive tasks using a total of 48 blocks (12 tasks × 4 levels) for at least 1.5 h per day, 5 days per week. All participants in the intervention group were given BBT tasks that gradually increased in difficulty level, which they submitted through a smartphone application daily for 16 weeks. The researchers monitored the participants' task performance records on the website and encouraged participants to engage in cognitive training through regular contact. This study was conducted to investigate the improvement in cognitive function and the activation pattern of the frontal cortex in older adults participating in smartphone application-based cognitive training. The cognitive assessment tool was the BeauBrain cognitive screening test (CST), a tablet-based computerized cognitive screening test. The activation pattern of the frontal cortex was measured using functional near-infrared spectroscopy (fNIRS). Additionally, this study aimed to determine the positive effects of cognitive training on everyday functioning and psychological states using a questionnaire. Results: Of 101 participants, 85 older adults without dementia (84.1%) who completed the study protocol were included in the statistical analysis. There were 41 participants (80.3%) in the intervention group and 44 participants (88.0%) in the control group. A two-way repeated-measures analysis of variance (ANOVA) was used to compare the cognitive scores over a 16-week period between the intervention and control groups. According to the CST results, the intervention group exhibited a statistically significant increase in the language subtest scores, specifically the phonemic word fluency test, compared to those of the control group. The fNIRS results revealed greater activation in the dorsolateral prefrontal cortex during the STROOP incongruent task in the intervention group than did the control group. However, the effectiveness of cognitive training was not observed across a variety of rating scales, including everyday functioning, depression, self-efficacy, attention, and subjective memory complaints. Conclusion: This study revealed that a smartphone-based cognitive training application led to improvements in phonemic generative naming ability and activation of the prefrontal cortex in older adults without dementia. This study is meaningful because it confirmed that cognitive training is partially effective in enhancing frontal lobe function. It also provided information on the brain mechanisms related to the effects of cognitive training using fNIRS.

Clinical staging of semantic dementia in an FDG-PET study using FTLD-CDR.

BACKGROUND: The frontotemporal lobar degeneration-specific clinical dementia rating (FTLD-CDR), which was recently developed to measure frontotemporal dementia (FTD) severity, includes 2 items that assess language and behavior in addition to the 6 items of the conventional CDR. METHODS: To investigate which of the 3 ratings, i.e. the global score of the CDR (GCDR), the behavioral domain score of the FTLD-CDR (BCDR), or the language domain score of the FTLD-CDR (LCDR), is most suitable for monitoring the progression of semantic dementia (SD), the number of hypometabolic voxels was calculated by comparing 28 SD patients in each stage of the 3 ratings with 63 age/sex-matched controls using voxel-based statistical parametric mapping. RESULTS: The hypometabolic areas increased as a function of the LCDR score in SD patients. However, hypometabolic areas associated with the GCDR did not increase gradually as the stage increased. Furthermore, those associated with the BCDR showed the reverse pattern. CONCLUSION: Our findings suggest that the severity and patterning of glucose hypometabolism measured by the LCDR correspond well with the natural course of SD reported in previous clinical and neuroimaging studies, whereas the BCDR and GCDR did not reflect disease progression in SD.

Eye-Tracking Metrics for Figure-Copying Processes in Early- vs. Late-Onset Alzheimer's Disease.

Visuospatial dysfunction is a common symptom in patients with Alzheimer's disease (AD). To more focus on copying processes rather than on finally completed figures, we conceptually split the copying processes into three stages: visuoperceptual function, visuoconstructional function, and working memory function. We constructed perceptual and working spaces to investigate the different stages of copying, and then, we compared the number and duration of fixations and saccades and the number of switches across the two spaces. We used eye-tracking glasses to assess eye-tracking metrics in patients with early-onset AD (EOAD), patients with late-onset AD (LOAD), and normal control (NC) participants while they copied the simplified Rey-Osterrieth complex figure test (RCFT). Regarding eye metrics on the perceptual space, the number and duration of fixations were greater in both groups of patients with AD than in the NC participants group (number: EOAD vs. NC: p < 0.001, LOAD vs. NC: p = 0. 003/ duration: EOAD vs. NC: p < 0.001, LOAD vs. NC: p < 0.001). On the working space, the number and duration of fixations were greater in the patients with EOAD than in the patients with LOAD and NC participants (number: EOAD vs. LOAD: p = 0. 007, EOAD vs. NC: p = 0. 001/duration: EOAD vs. LOAD: p = 0. 008, EOAD vs. NC: p = 0. 002). The number of saccades and switching was higher in patients with EOAD than in NC participants (p < 0.001). The eye-tracking metrics from the simplified RCFT correlated with the neuropsychological test scores. Patients with EOAD and LOAD achieved the same level of performance at the simplified and original RCFT scores. However, patients with EOAD than LOAD showed a greater number and duration of fixations on the working space and more frequent switching between the perceptual and working spaces, which may reflect more cognitive efforts to achieve the same level of performance.