Structural brain network correlations with amyloid burden in elderly individuals at risk of Alzheimer's disease.

Alzheimer's disease (AD) has a long preclinical phase during which beta-amyloid accumulates in the brain without cognitive impairment. However, the pattern of brain network alterations in this early stage of the disease remains to be clarified. In this study we examined the relationships between regional brain network indices and beta-amyloid deposits. Twenty-four elderly subjects with the APOE4 allele underwent both a 1.5-Tesla magnetic resonance imaging (MRI) scan and a positron emission tomography (PET) scan using [18F]Florbetapir. We computed network metrics such as the degree, betweenness centrality, and clustering coefficient, and examined the relationships between the beta-amyloid accumulation and these regional brain network connectivity metrics. We found a significant positive correlation between the global standardized uptake value ratio (SUVR) of [18F]Florbetapir and the betweenness centrality in the left parietal region. However, there were no significant correlations between the SUVR score and other network indices or the regional gray matter volume. Our data suggest a relationship between the beta-amyloid accumulation and the regional brain network connectivity in subjects at risk of AD. The brain connectome may provide an adjunct biomarker for the early detection of AD.

Tablet-Based Automatic Assessment for Early Detection of Alzheimer's Disease Using Speech Responses to Daily Life Questions.

Health-monitoring technologies for automatically detecting the early signs of Alzheimer's disease (AD) have become increasingly important. Speech responses to neuropsychological tasks have been used for quantifying changes resulting from AD and differentiating AD and mild cognitive impairment (MCI) from cognitively normal (CN). However, whether and how other types of speech tasks with less burden on older adults could be used for detecting early signs of AD remains unexplored. In this study, we developed a tablet-based application and compared speech responses to daily life questions with those to neuropsychological tasks in terms of differentiating MCI from CN. We found that in daily life questions, around 80% of speech features showing significant differences between CN and MCI overlapped those showing significant differences in both our study and other studies using neuropsychological tasks, but the number of significantly different features as well as their effect sizes from life questions decreased compared with those from neuropsychological tasks. On the other hand, the results of classification models for detecting MCI by using the speech features showed that daily life questions could achieve high accuracy, i.e., 86.4%, comparable to neuropsychological tasks by using eight questions against all five neuropsychological tasks. Our results indicate that, while daily life questions may elicit weaker but statistically discernable differences in speech responses resulting from MCI than neuropsychological tasks, combining them could be useful for detecting MCI with comparable performance to using neuropsychological tasks, which could help develop health-monitoring technologies for early detection of AD in a less burdensome manner.

Structural Brain Network Correlated with Reading Impairment in Alzheimer's Disease.

AIM: Alzheimer's disease (AD) is the most common age-related neurodegenerative disease and leads to dementia. AD is characterized by progressive declines in memory and, as the disease progresses, language dysfunction. Although it has been reported that AD patients show progressive aphasia, no study has examined the relationship between language functions estimated by the Standard Language Test for Aphasia (SLTA) and brain network connectivity in Japanese AD patients. If present, such a relationship would be of particular interest because Japanese speakers are accustomed to mingling ideography and phonography. METHODS: 22 Japanese patients with AD who underwent 1.5-tesla MRI scan and SLTA, the scale for speech and reading impairment, participated in this study. We computed brain network connectivity metrics such as degree, betweenness centrality, and clustering coefficient, and estimated their relationships with the subscores of SLTA. RESULTS: There was a significant negative correlation between the score for "reading aloud Kanji words" and the clustering coefficient in the left inferior temporal region, bilateral hippocampal regions, and right parietotemporal region. We also found a significant negative correlation between the score for "auditory comprehension of words" and the clustering coefficient in the left prefrontal region. No significant relationship was found between the other SLTA scores and the network metrics. CONCLUSIONS: Our data suggest relationships between reading impairments and regional brain network connectivity in Japanese patients with AD. The brain connectome may provide adjunct biological information that could improve our understanding of reading impairment.

Handwriting Features of Multiple Drawing Tests for Early Detection of Alzheimer's Disease: A Preliminary Result.

Early detection of Alzheimer's disease (AD) has become increasingly important. Healthy monitoring technology focusing on behavioral changes is a promising approach in this vein. Among such technologies, handwriting features measured by digital tablet devices have attracted attention as potential indicators for detecting AD and mild cognitive impairment (MCI). However, previous studies have mainly investigated features in single tasks, and it remains unclear whether combining the features of multiple tasks could improve the performance of detecting AD and MCI. In this study, we investigated features in five representative tasks used in neuropsychological tests collected from 71 seniors including some diagnosed with MCI and AD. We found that our three-class classification model improved diagnosis accuracy by up to 11.3% by combining features of multiple tasks, for a final accuracy of 74.6%. We also suggested that drawing behaviors during multiple tasks might be useful for estimating disease progression simply by utilizing the labels of disease groups.

Multimodal Behavior Analysis Towards Detecting Mild Cognitive Impairment: Preliminary Results on Gait and Speech.

Behavioral analysis for identifying changes in cognitive and physical functioning is expected to help detect dementia such as mild cognitive impairment (MCI) at an early stage. Speech and gait features have been especially recognized as behavioral biomarkers for dementia that possibly occur early in its course, including MCI. However, there are no studies investigating whether exploiting the combination of multimodal behavioral data could improve detection accuracy. In this study, we collected speech and gait behavioral data from Japanese seniors consisting of cognitively healthy adults and patients with MCI. Comparing the models using single modality behavioral data, we showed that the model using multimodal behavioral data could improve detection by up to 5.9%, achieving 82.4% accuracy (chance 55.9%). Our results suggest that the combination of multimodal behavioral features capturing different functional changes resulting from dementia might improve accuracy and help timely diagnosis at an early stage.

Using Tablet-Based Assessment to Characterize Speech for Individuals with Dementia and Mild Cognitive Impairment: Preliminary Results.

Early detection of dementia as well as improvement in diagnosis coverage has been increasingly important. Previous studies involved extracting speech features during neuropsychological assessments by humans, such as medical pro- fessionals, and succeeded in detecting patients with dementia and mild cognitive impairment (MCI). Enabling such assessment in an automated fashion by using computer devices would extend the range of application. In this study, we developed a tablet-based application for neuropsychological assessments and collected speech data from 44 Japanese native speakers including healthy controls (HCs) and those with MCI and dementia. We first extracted acoustic and phonetic features and showed that several features exhibited significant difference between HC vs. MCI and HC vs. dementia. We then constructed classification models by using these features and demonstrated that these models could differentiate MCI and dementia from HC with up to 82.4 and 92.6% accuracy, respectively.

Prevalence of childhood obstructive sleep apnea syndrome and its role in daytime sleepiness.

OBJECTIVES: To investigate childhood obstructive sleep apnea syndrome (OSAS) and its role in daytime sleepiness among school-age children. METHODS: A questionnaire survey was conducted with 25,211 children aged 6-15 (mean, 10.39) years attending 148 elementary and 71 middle schools in 10 prefectures across Japan and their parents. Questions concerned 4 sleep habit items (bedtime, sleep onset latency, wake time after sleep onset, wake-up time) and 4 sleep disorder items (loud snoring, snorts/gasps, breathing pauses, seems very sleepy in the daytime). Total sleep time (TST) was calculated with sleep habits. Severe possible OSAS (p-OSAS) was defined as having loud snoring, snorts and gasps, or breathing pauses "frequently" (≥ 5 times per week), and mild p-OSAS was rated as having any of these "sometimes" (2-4 times per week). Severe daytime sleepiness was defined as seeming very sleepy "frequently" and mild daytime sleepiness as seeming very sleepy "sometimes". RESULTS: Mean prevalence of mild to severe p-OSAS and severe p-OSAS in children across all grade levels was 9.5% and 1.6%, respectively. p-OSAS was particularly prevalent in children at lower elementary levels, decreasing with advancing grade levels. Prevalence of mild and severe daytime sleepiness was 6.1% and 0.9%, respectively, among all children (7.0%). Prevalence of daytime sleepiness increased with advancing grade levels, particularly in middle-school level. Average TST was 8.4 ± 2.2 h in both elementary and middle-school levels, and decreased as grades advanced, particularly in middle-school levels. Multivariate logistic regression analysis showed that middle-school level, TST < 8 h, and p-OSAS were independent factors for daytime sleepiness. Strong correlations were found between severe daytime sleepiness and severe p-OSAS or TST < 6 h, and between daytime sleepiness and loud snoring or breathing pauses. CONCLUSION: p-OSAS may be an independent factor influencing daytime sleepiness in school-age children. Loud snoring and breathing pauses could be clinical markers for children with severe daytime sleepiness.