To explore neurophysiological biomarkers of Alzheimer's disease (AD), we investigated electroencephalography (EEG) of AD patients, and assessed lagged phase synchronization, a measure of brain functional connectivity. Twenty-eight probable AD patients and 30 healthy controls (HC) were enrolled. Forty seconds of artifact-free EEG data were selected and compared between patients with AD and HC. Current source density (CSD) and lagged phase synchronization were analyzed by using eLORETA. Patients with AD showed significantly decreased lagged phase synchronization between most cortical regions in delta band relative to controls. There also was a decrease in lagged phase synchronization between the right dorsolateral prefrontal cortex (DLPFC) and the right posterior-inferior parietal lobule (pIPL) in theta band. In addition, some connections in delta band were found to be associated with cognitive function, measured by MMSE. This involved specifically interhemispheric temporal connections as well as left inferior parietal connectivity with the left hippocampus, lateral frontal regions, and the anterior cingulate cortex (aCC). Right temporal connections in delta band were related to global function, as estimated by CDR. No differences were found in CSD analysis between patients and HC. Functional connectivity disruptions between certain brain regions, as measured with lagged phase synchronization, may potentially represent a neurophysiological biomarker of AD. Our study indicated that AD and healthy elderly could have the different patterns of lagged phase synchronization.

Behavioral and psychological symptoms of dementia (BPSDs) negatively impact the prognosis of dementia patients and increase caregiver distress. The aims of this study were to clarify the differences of trajectories of 12 kinds of BPSDs by disease severity in four major dementias and to develop charts showing the frequency, severity, and associated caregiver distress (ACD) of BPSDs using the data of a Japan multicenter study (J-BIRD). We gathered Neuropsychiatric Inventory (NPI) data of patients with Alzheimer’s disease (AD; n = 1091), dementia with Lewy bodies (DLB; n = 249), vascular dementia (VaD; n = 156), and frontotemporal lobar degeneration (FTLD; n = 102) collected during a 5-year period up to July 31, 2013 in seven centers for dementia in Japan. The NPI composite scores (frequency × severity) of 12 kinds of items were analyzed using a principal component analysis (PCA) in each dementia. The factor scores of the PCA were compared in each dementia by disease severity, which was determined with Clinical Dementia Rating (CDR). Significant increases with higher CDR scores were observed in 1) two of the three factor scores which were loaded for all items except euphoria in AD, 2) two of the four factor scores for apathy, aberrant motor behavior (AMB), sleep disturbances, agitation, irritability, disinhibition, and euphoria in DLB, and 3) one of the four factor scores for apathy, depression, anxiety, and sleep disturbances in VaD. However, no increases were observed in any of the five factor scores in FTLD. As dementia progresses, several BPSDs become more severe, including 1) apathy and sleep disturbances in AD, DLB, and VaD, 2) all of the BPSDs except euphoria in AD, 3) AMB, agitation, irritability, disinhibition, and euphoria in DLB, and 4) depression and anxiety in VaD. Trajectories of BPSDs in FTLD were unclear.

Background/Objective: Behavioral and psychological symptoms of dementia (BPSD) have been reported to affect caregiver burden in patients with dementia with Lewy bodies (DLB). However, the factor structure of BPSD and the factors that affect caregiver burden in DLB remain unknown. This study sought to classify BPSD and to reveal what type of BPSD affects caregiver burden in patients with DLB.Methods: We collected data on neuropsychiatric inventory-plus (NPI-plus), Zarit Burden Interview (ZBI), Mini-Mental State Examination (MMSE), Lawton's Instrumental Activities of Daily Living and Physical Self-Maintenance Scale (IADL/PSMS), age, and sex of 102 patients with probable DLB. An exploratory factor analysis of 13 items of the NPI-plus was carried out to classify BPSD. Multivariate regression analyses were conducted to extract the clinical variables related to caregiver burden, including factors resulting from the aforementioned factor analysis.Results: The mean age and MMSE score were 78.6 (5.6) and 20.2 (5.2), respectively. Factor analysis revealed four factors of “psychosis,” “affection,” “wakefulness,” and “hyperactivity.” “Psychosis” and “affection” factors as well as MMSE, IADL, and PSMS were significantly associated with ZBI. Multivariate regression analyses revealed that the total score of ZBI was associated with “psychosis,” “affection,” and IADL, that the personal strain score of ZBI was associated with “affection” and IADL, and that the role strain score of ZBI was associated with “wakefulness” and IADL.Conclusions: BPSD in DLB consists of three factors common to Alzheimer's disease and a specific “wakefulness” factor. In addition to IADL, each BPSD factor would affect caregiver burden in different ways in DLB.