Cerebral Microbleeds Are Associated with Cerebral Hypoperfusion in Patients with Alzheimer's Disease.

BACKGROUND: Although cerebral microbleeds (CMBs) are commonly observed in patients with Alzheimer's disease (AD), their clinical relevance for AD remains unclear. OBJECTIVE: We investigated the significance of CMBs in AD by examining the relationship between CMBs and cerebral blood flow (CBF) in patients with AD. METHODS: Thirty-four patients (aged 77.9±7.6 years; 17 men) with probable AD and multiple (≥8) CMBs were selected from 394 consecutive patients. For each lobe of the brain, the correlation between the number of CMBs observed on susceptibility-weighted images and the decrease in CBF observed on single-photon emission computed tomography was assessed. RESULTS: The number of microbleeds was significantly correlated with the severity of decrease in the occipital lobe (Spearman's r = 0.531, p < 0.001) and temporal lobe (r = 0.437, p < 0.001) but not in the frontal lobe (r = 0.201, p = 0.101) and parietal lobe (r = 0.178, p = 0.146). These results were unchanged in the partial correlational analysis after controlling the effect of other small vessel disease such as lacunars and white matter hyperintensities. CONCLUSION: Multiple CMBs are associated with cerebral hypoperfusion in AD. The effects of CMBs on CBF differed according to brain location, possibly reflecting different distributions of the underlying cerebral amyloid angiopathy and AD-related histopathology, such as neurofibrillary tangles.

Clinical Features of Auditory Hallucinations in Patients With Dementia With Lewy Bodies: A Soundtrack of Visual Hallucinations.

OBJECTIVE: Auditory hallucinations are an important symptom for diagnosing dementia with Lewy bodies (DLB), yet they have received less attention than visual hallucinations. We investigated the clinical features of auditory hallucinations and the possible mechanisms by which they arise in patients with DLB. METHODS: We recruited 124 consecutive patients with probable DLB (diagnosis based on the DLB International Workshop 2005 criteria; study period: June 2007-January 2015) from the dementia referral center of Kumamoto University Hospital. We used the Neuropsychiatric Inventory to assess the presence of auditory hallucinations, visual hallucinations, and other neuropsychiatric symptoms. We reviewed all available clinical records of patients with auditory hallucinations to assess their clinical features. We performed multiple logistic regression analysis to identify significant independent predictors of auditory hallucinations. RESULTS: Of the 124 patients, 44 (35.5%) had auditory hallucinations and 75 (60.5%) had visual hallucinations. The majority of patients (90.9%) with auditory hallucinations also had visual hallucinations. Auditory hallucinations consisted mostly of human voices, and 90% of patients described them as like hearing a soundtrack of the scene. Multiple logistic regression showed that the presence of auditory hallucinations was significantly associated with female sex (P = .04) and hearing impairment (P = .004). The analysis also revealed independent correlations between the presence of auditory hallucinations and visual hallucinations (P < .001), phantom boarder delusions (P = .001), and depression (P = .038). CONCLUSIONS: Auditory hallucinations are common neuropsychiatric symptoms in DLB and usually appear as a background soundtrack accompanying visual hallucinations. Auditory hallucinations in patients with DLB are more likely to occur in women and those with impaired hearing, depression, delusions, or visual hallucinations.

Mental health among younger and older caregivers of dementia patients.

AIM: Caregiver burden in dementia is an important issue, but few studies have examined the mental health of younger and older family caregivers by comparing them with age- and gender-matched community residents. We aimed to compare the mental health of dementia caregivers with that of community residents and to clarify factors related to mental health problems in younger and older caregivers. METHODS: We studied 104 dementia caregivers; 46 were younger (<65 years) and 58 were older (≥65 years). A total of 104 community residents who were matched for age and gender were selected. We compared depression (Center for Epidemiologic Studies Depression Scale for younger participants; Geriatric Depression Scale for older participants), health-related quality of life (QOL) short-form health survey (SF-8), sleep problems, and suicidal ideation between the caregivers and community residents by age. Behavioural and psychological symptoms of dementia, activities of daily living (ADL), and instrumental ADL were assessed among patients with dementia using the Neuropsychiatric Inventory, Physical Self-Maintenance Scale, and Lawton Instrumental ADL Scale, respectively. RESULTS: According to SF-8 results, both younger and older caregivers had significantly worse mental QOL than community residents (younger caregivers: 46.3 vs community residents: 49.7, P = 0.017; older caregivers: 48.2 vs community residents: 51.1, P = 0.024) but were not more depressive. Sleep problems were significantly more frequent in younger caregivers (39.1%) than in community residents (17.0%) (P = 0.017). Multiple regression analysis revealed that caregivers' deteriorated mental QOL was associated with patients' behavioural and psychological symptoms of dementia in younger caregivers and with dementia patients' instrumental ADL and female gender in older caregivers. CONCLUSIONS: Dementia caregivers had a lower mental QOL than community residents. To maintain caregivers' mental QOL, it is necessary to provide younger caregivers with skills or professional interventions for dealing with behavioural and psychological symptoms of dementia, and older caregivers must be offered adequate care support.

Sleep disturbances are key symptoms of very early stage Alzheimer disease with behavioral and psychological symptoms: a Japan multi-center cross-sectional study (J-BIRD).

BACKGROUND: Sleep disturbances in Alzheimer disease (AD) may affect behavioral and psychological symptoms of dementia (BPSD). Our aim was to elucidate the associations between sleep disturbances and other BPSD at different stages of AD. METHODS: This investigation was part of a multicenter-retrospective study in Japan (J-BIRD). Eligible for final analyses were 684 AD patients. Global severity of dementia was estimated using the Clinical Dementia Rating (CDR) scale. BPSD were assessed using the Neuropsychiatric Inventory (NPI). We analyzed the relationships between sleep disturbances and BPSD at different stages of AD according to the CDR score. RESULTS: Among the 684 AD patients, 146 (21.3%) had sleep disturbances. Patients with very early AD (CDR 0.5) and sleep disturbances had significantly more BPSD than those without sleep disturbances, as indicated by the higher prevalence of the following four NPI items: anxiety, euphoria, disinhibition, and aberrant motor behavior. In AD at CDR 2, (moderate AD) only one NPI item (irritability) was affected, while none was affected at CDR 1 (mild AD) and 3 (severe AD). Multiple regression analyses were performed in those with AD having various CDR scores. At CDR 0.5, the presence of sleep disturbances was associated with a high total NPI score (ß = 0.32, p < 0.001). However, other factors, including cognitive decline, age, gender, and years of education, were not significantly associated with the NPI score. At CDR 1 and 2, no factor was significantly related to BPSD. CONCLUSION: Sleep disturbances were strongly associated with other BPSD in the very early stage of AD. Copyright © 2016 John Wiley & Sons, Ltd.

Differences of Behavioral and Psychological Symptoms of Dementia in Disease Severity in Four Major Dementias.

BACKGROUND/AIMS: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Malnutrition in Alzheimer's Disease, Dementia with Lewy Bodies, and Frontotemporal Lobar Degeneration: Comparison Using Serum Albumin, Total Protein, and Hemoglobin Level.

Malnutrition among dementia patients is an important issue. However, the biochemical markers of malnutrition have not been well studied in this population. The purpose of this study was to compare biochemical blood markers among patients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). A total of 339 dementia outpatients and their family caregivers participated in this study. Low serum albumin was 7.2 times more prevalent among patients with DLB and 10.1 times more prevalent among those with FTLD than among those with AD, with adjustment for age. Low hemoglobin was 9.1 times more common in female DLB patients than in female AD patients, with adjustment for age. The levels of biochemical markers were not significantly correlated with cognitive function. Family caregivers of patients with low total protein, low albumin, or low hemoglobin were asked if the patients had loss of weight or appetite; 96.4% reported no loss of weight or appetite. In conclusion, nutritional status was worse in patients with DLB and FTLD than in those with AD. A multidimensional approach, including blood testing, is needed to assess malnutrition in patients with dementia.

Relationship between dementia severity and behavioural and psychological symptoms in early-onset Alzheimer's disease.

BACKGROUND: The features of behavioural and psychological symptoms of dementia (BPSD) are influenced by dementia stage. In early-onset Alzheimer's disease (EOAD), the association between BPSD and dementia stage remains unclear because of the difficulty of recruiting subjects with a wide range of disease severity. We used a combination of community-based and hospital-based approaches to investigate the relationship between dementia severity and BPSD in EOAD patients. METHODS: Sixty-three consecutive EOAD outpatients and 29 EOAD patients from a community-based survey were divided into three dementia severity groups according to the Clinical Dementia Rating scale (CDR): mild (CDR 0.5-1, n = 55), moderate (CDR 2, n = 17), and severe (CDR 3, n = 20). BPSD were rated using the Neuropsychiatric Inventory. RESULTS: Scores of the Neuropsychiatric Inventory subscales agitation, euphoria, apathy, disinhibition, irritability, and aberrant motor behaviour increased significantly with increased dementia severity. Hallucinations were greater in the moderate group than in the mild group. For delusions, depression, and anxiety, no significant differences were observed among the three severity groups. CONCLUSIONS: The pattern of apathy, agitation, disinhibition, irritability, and aberrant motor behaviour worsening with severity progression in EOAD is similar to the pattern in late-onset Alzheimer's disease. In contrast, hallucinations, depression, and anxiety showed different patterns in EOAD.