Kaori Iwata

Early functional network alterations in asymptomatic elders at risk for Alzheimer’s disease

Amyloid-β (Aβ) deposition is known to starts decades before the onset of clinical symptoms of Alzheimer’s disease (AD), however, the detailed pathophysiological processes underlying this preclinical period are not well understood. This study aimed to investigate functional network alterations in cognitively intact elderly individuals at risk for AD, and assessed the association between these network alterations and changes in Aβ deposition, glucose metabolism, and brain structure. Forty-five cognitively normal elderly subjects, who were classified into Aβ-positive (CN+) and Aβ-negative (CN−) groups using 11C-Pittsburgh compound B PET, underwent resting state magnetoencephalography measurements, 18F-fluorodeoxyglucose PET (FDG-PET) and structural MRI. Results demonstrated that in the CN+ group, functional connectivity (FC) within the precuneus was significantly decreased, whereas it was significantly enhanced between the precuneus and the bilateral inferior parietal lobules in the low-frequency bands (theta and delta). These changes were suggested to be associated with local cerebral Aβ deposition. Most of Aβ+ individuals in this study did not show any metabolic or anatomical changes, and there were no significant correlations between FC values and FDG-PET or MRI volumetry data. These results demonstrate that functional network alterations, which occur in association with Aβ deposition, are detectable using magnetoencephalography before metabolic and anatomical changes are seen.

Electromagnetic signatures of the preclinical and prodromal stages of Alzheimer’s disease

Biomarkers relevant to the pre-dementia stages of Alzheimer’s disease are needed. Using MEG, PET, and MRI, Nakamura et al. disentangle resting state regional spectral patterns in cognitively normal subjects and individuals with mild cognitive impairment into MEG signatures related to Aβ deposition, disease progression, or changes non-specific to Alzheimer’s disease.

Smaller Hippocampal Volume and Degraded Peripheral Hearing Among Japanese Community Dwellers

A growing body of literature has demonstrated that dementia and hearing loss are interrelated. Recent interest in dementia research has expanded to brain imaging analyses with auditory function. The aim of this study was to investigate the link between hearing ability, which was assessed using pure-tone audiometry, and the volume of brain regions, specifically the hippocampus, entorhinal cortex, Heschl’s gyrus, and total gray matter, using Freesurfer software and T1-weighted brain magnetic resonance imaging. The data for 2082 samples (age range = 40–89 years) were extracted from a population-based cohort of community dwellers. Hearing-impaired individuals showed significantly smaller hippocampal volumes compared with their non-hearing-impaired counterparts for all auditory frequency ranges. In addition, a correlational analysis showed a significant dose-response relationship for hearing ability and hippocampal volume after adjusting for potential confounding factors so that the more degraded the peripheral hearing was, the smaller the hippocampal volume was. This association was consistent through the auditory frequency range. The volume of the entorhinal cortex, right Heschl’s gyrus and total gray matter did not correlate with hearing level at any frequency. The volume of the left Heschl’s gyrus showed a significant relationship with the hearing levels for some auditory frequencies. The current results suggested that the presence of hearing loss after middle age could be a modifier of hippocampal atrophy.

THE EFFECT OF AGE AND SEX ON EVALUATION OF HIPPOCAMPAL ATROPHY IN NORMAL AND MILD ALZHEIMER’S DISEASE DEMENTIA: A J-ADNI STUDY

intrinsic brain activity reflected by ALFF/fALFF levels were detected in SCD, aMCI and d-AD. As disease progressed, the number of brain regions with changed ALFF/fALFF levels was increasing and the extent of disturbances get heavier. In SCD, the ALFF/ fALFF levels of frontal lobe were positively correlated with the neurophysiological tests. Decreased ALFF/fALFF levels in brain regions closely related to impaired episodic memory were found in aMCI and d-AD. Conclusions:Our study may indicate continuous breakdown of spontaneous brain activity during the disease progression of AD. The ALFF/fALFF changes can characterize the physiology of AD and may potentially provide implications for AD therapeutics.

Decreased Glucose Metabolism in Medial Prefrontal Areas is Associated with Nutritional Status in Patients with Prodromal and Early Alzheimer’s Disease

BACKGROUND Weight loss is frequently observed in patients with Alzheimers disease (AD); however, the underlying mechanisms are not well understood. OBJECTS To clarify the associations between nutritional status and AD-related brain changes using Pittsburgh Compound-B (PiB)-PET, fluorodeoxyglucose (FDG)-PET, and structural MRI. METHODS The subjects were 34 amyloid-β (Aβ)-positive individuals with mild cognitive impairment or early AD (prodromal/early AD), and 55 Aβ-negative cognitively normal (CN) subjects who attended the Multimodal Neuroimaging for AD Diagnosis (MULNIAD) study. Nutritional status of the subjects was assessed by body mass index and waist to height ratio (waist circumference/height). The associations between nutritional status and brain changes were examined by multiple regression analysis using statistical parametric mapping. RESULTS In the prodromal/early AD group, nutritional status was significantly positively correlated with regional cerebral glucose metabolism (rCGM) in the medial prefrontal cortices, while different topographical associations were seen in the CN group, suggesting these changes were AD-specific. Aβ deposition and gray matter volume were not significantly associated with nutritional status. Sub-analysis in the prodromal/early AD group demonstrated that fat mass index, but not fat-free mass index, was positively correlated with rCGM in the medial prefrontal areas. CONCLUSION This present study provides preliminary results suggesting that hypometabolism in the medial prefrontal areas is specifically associated with AD-related weight loss, and decrease in fat mass may have a key role.

Age-Related Changes in Attentional Control Using an N-Back Working Memory Paradigm

Background/Study Context: Older adults tend to be affected by task-irrelevant distracters. However, whether or not this aging effect is evident when task-irrelevant and relevant stimuli are presented across different sensory modalities is still a subject of debate. The purpose of the present study was to clarify age-related differences in the effects of auditory distraction on visual information processing. Methods: Participants included 20 young individuals, 20 younger-old individuals in their 60s, and 20 older-old individuals in their 70s. Visual n-back (1-back, 2-back) working memory (WM) tasks using Japanese words were examined with and without auditory distracter conditions. Participants’ performances were analyzed using a three-way analysis of variance: 3 (age group) × 2 (distraction) × 2 (working memory load). Results: The effects of auditory distractions were influenced by aging and WM load. Auditory distractions disturbed WM performances preferentially in older adults. Further, participants in the older-old group were more affected by auditory distractions than those in the younger-old group, especially during the 2-back task. Conclusion: These results suggested that the WM performances for visual n-back tasks were largely disturbed by auditory distractions in older adults but not in young adults.

ALTERED REGIONAL CEREBRAL GLUCOSE METABOLISM IN PATIENTS WITH PRODROMAL AND EARLY ALZHEIMER’S DISEASE ASSOCIATED WITH NUTRITIONAL STATUS

lobe atrophy and F -AV1451 PET imaging revealed uptake in the temporal and frontal lobes, as well as in the basal ganglia (Fig 1 C). The regional uptake of F -AV1451 correlated strongly with the tau aggregates revealed using immunohistochemistry (R 1⁄4 0.80, P < 0.01; Fig 2). All cases exhibited negative amyloid (F -flutemetamol) PET scans. Conclusions:The in vivo uptake of F-AV1451 reflects the regional amount of tau aggregates revealed by neuropathological examination. Further, tau pathology inMAPT mutation carriers is accurately detected with F -AV1451 PET, which consequently can be used to track the effects of anti-tau therapies in this patient group.

Amyloid deposition and ApoE4 carriers in idiopathic normal pressure hydrocephalus

It is known that idiopathic normal pressure hydrocephalus (iNPH) can co-morbid with Alzheimer disease (AD). Previous studies, probing amyloid (Aβ) deposition by cortical biopsy during a ventriculo-peritoneal shunt, have shown that Aβ deposition was found in 40~45 % of iNPH patients. However, the reason for this high prevalence is not well understood. Therefore, the objective of this study was to investigate whether the prevalence of the Aβ deposition in iNPH is explainable by a simple overlap of the AD pathology in general population, or is modified by some specific effects of iNPH.

CORRELATION BETWEEN CORTICAL EXCITABILITY AND LOCAL β-AMYLOID DEPOSITION AS EVALUATED BY MEG AND PIB-PET

P4-117 CORRELATION BETWEEN CORTICAL EXCITABILITYAND LOCAL b-AMYLOID DEPOSITION AS EVALUATED BY MEG AND PIB-PET Akinori Nakamura, Takashi Kato, Misako Yamagishi, Kaori Iwata, Masahiko Bundo, Kimiko Kato, Hideyuki Hattori, Takashi Sakurai, Yutaka Arahata, Maess Burkhard, Kengo Ito, Study Group MULNIAD, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan; National Center for Geriatrics and Gerontology, Obu, Aichi, Japan; Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. Contact e-mail: nakamura@ncgg.go.jp