Awareness of the COVID-19 Outbreak and Resultant Depressive Tendencies in Patients with Severe Alzheimer's Disease.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has substantially affected patients with dementia and their caregivers. However, we found not all Alzheimer's disease (AD) patients were afraid of COVID-19 infection. Therefore, we investigated the association between rate of awareness of COVID-19 and depressive tendency in AD. 126 consecutive outpatients with AD were enrolled in this study from May 25, on the day when the declaration of emergency was lifted in Japan, through June 30, 2020. In addition to routine psychological tests, the participants were asked the following two questions: "Do you know COVID-19?" and "Why are you wearing a face mask?". Moderate to severe AD patients were found to have a low COVID-19 recognition rate and did not fully understand why they were wearing face masks. In addition, because they did not understand the seriousness of the COVID-19 outbreak, their Geriatric Depression Scale scores were also substantially lower. These results may appear to simply indicate that people with severe dementia are unaware of current events. However, these results provide insights into how to care for patients with dementia and how to allocate the time and support of our limited staff during the COVID-19 outbreak.

Effects of 12-month exercise intervention on physical and cognitive functions of nursing home residents requiring long-term care: a non-randomised pilot study.

AIMS: We performed a 12-month exercise intervention for 'nursing home for the elderly' residents requiring long-term care. We evaluated changes in their muscular strength, muscle mass, and cognitive function. METHODS: Thirty-seven nursing home residents (Mini-Mental State Examination (MMSE): 14.7 ± 7.0, Barthel Index: 44.2 ± 18.9) were enrolled. We divided the participants into the exercise intervention group (n = 19) and non-intervention group (n = 18) ensuring no significant difference in the participants' characteristics at baseline. For the exercise intervention group, exercise was performed for about 40 min twice a week for 12 months. Skeletal Mass Index and grip force were determined to evaluate muscle mass and muscle strength, respectively. MMSE, Trail Making Test (TMT) part A, and Geriatric Depression Scale 15 (GDS15) were used for cognitive function evaluation, with their changes investigated. RESULTS: After 12 months, the MMSE scores were significantly improved in the exercise intervention group compared with the non-intervention group (change from baseline to 12 months: Non-intervention: -1.0 ± 2.8, Intervention: 1.2 ± 3.0; P = 0.04). Moreover, the grip force of the dominant arm was significantly improved in the exercise intervention group compared with the non-intervention group (change from baseline to 12 months: Non-intervention: -1.3 ± 2.8 kg, Intervention: 1.4 ± 4.6 kg; P = 0.007). The prevalence of sarcopenia was significantly increased after 12 months compared with baseline in the non-intervention group (Non-intervention: 61.1% → 75.0%, Intervention: 77.8% → 71.4%; P < 0.02). There were no significant changes in GDS15, Barthel Index and TMT after 12 months in intervention and non-intervention groups. CONCLUSION: Exercise intervention may be effectively used for improving the physical and cognitive functions of nursing home residents requiring long-term care.

Positive Association Between Cognitive Function and Cerebrospinal Fluid Orexin A Levels in Alzheimer's Disease.

BACKGROUND: Recently, many studies have investigated the association between orexin A and Alzheimer's disease (AD). However, it remains to be determined whether the observed changes in orexin A levels are associated with pathological changes underlying AD, or cognitive function. In particular, a direct association between cerebrospinal fluid (CSF) orexin A levels and cognitive function has not been reported to date. OBJECTIVE: The aim of this study was to identify whether there is a direct association between the orexinergic system and cognitive function in AD. METHODS: For this study, we included 22 patients with AD and 25 control subjects who underwent general physical, neurological, and psychiatric examinations, neuroimaging, and CSF collection by lumbar puncture were enrolled. Correlations between CSF orexin A levels and CSF AD biomarker levels (i.e., levels of phosphorylated tau [p-tau], Aß42, and Aß42/Aß40) were assessed to confirm the results of previous studies. Moreover, the correlation between CSF orexin A levels and Mini-Mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) scores were analyzed. RESULTS: There was a significant positive correlation between CSF orexin-A levels and cognitive function (MMSE scores: r = 0.591, p = 0.04, MoCA score: r = 0.571, p = 0.006) in AD patients. CONCLUSION: This is the first study to our knowledge demonstrating an association between cognitive function and CSF orexin A levels in AD. Our results suggest the possibility that orexinergic system overexpression is not always a negative factor for cognitive function In AD.

Neuroimaging Characteristics of Frailty Status in Patients with Alzheimer's Disease.

BACKGROUND/OBJECTIVE: Although frailty is closely linked to dementia, particularly Alzheimer's disease (AD), underlying pathophysiology of frailty associated with AD remains uncertain. This study aimed to investigate differences in structural and functional brain imaging abnormalities between AD with and without frailty. METHODS: A total of 191 outpatients with probable AD (men: 91; women: 100; age: 80.7±6.3 years) who underwent both magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) were enrolled in this study. Frailty was determined in accordance with the Obu study Health Promotion for the Elderly. We compared numbers of small infarctions in the subcortical gray and white matter and severity of white matter abnormalities (periventricular hyperintensity [PVH] and deep white matter hyperintensity [DWMH]) on MRI, and regional cerebral blood flow (rCBF) changes on SPECT between AD with and without frailty. RESULTS: The prevalence of frailty was 43.4% in patients with AD. PVH and DWMH scores were significantly higher in AD with frailty compared to those without frailty. AD with frailty had a trend of decreased rCBF in the bilateral anterior cingulate gyrus, whereas those without frailty tend to have decreased rCBF in the left dominant parietal lobe and precuneus. CONCLUSION: Our MRI and SPECT imaging studies suggest different underlying pathophysiology in the brain between AD with frailty and without frailty.

Ambulatory glucose profile in diabetes-related dementia.

AIM: Diabetes-related dementia (DrD), a dementia subgroup associated with specific diabetes mellitus (DM)-related metabolic abnormalities rather than Alzheimer's disease (AD) pathology or cerebrovascular disease, is characterized by less well-controlled glycemia. We investigated the glucose level, variability and stability, and risk of hypoglycemia in DrD to determine characteristic ambulatory glucose profiles (AGP). METHODS: We obtained AGP for 14 days of 40 patients with AD associated with DM and 19 patients with DrD using a novel sensor-based flash glucose monitoring system (FreeStyle Libre Pro). RESULTS: Despite similar mean glucose and estimated A1c values, the DrD group showed significantly greater glucose variability and higher percentage of time spent in hypoglycemia than the AD associated with DM group. Glucose level and variability correlated significantly and negatively with Mini-Mental State Examination in DrD, but not in AD associated with DM The estimated A1c levels calculated from the 14 days of AGP data significantly correlated with the HbA1c levels measured within 2 months of the insertion of the sensor. CONCLUSIONS: DrD has a distinctively different AGP from that of AD associated with DM. Glucose variability and hypoglycemia are more involved in the pathophysiology of DrD than in that of AD associated with DM. The AGP analysis using the flash glucose monitoring system might provide useful information undetected by HbA1c values. Geriatr Gerontol Int 2019; 19: 282-286.

Sarcopenia and Muscle Functions at Various Stages of Alzheimer Disease.

Although sarcopenia is closely linked to dementia, particularly Alzheimer disease (AD), there are few studies examining the prevalence and associated factors of sarcopenia in subjects with AD. This study aimed to investigate the prevalence of sarcopenia, factors associated with sarcopenia in elderly subjects with AD, and differences in muscle functions of the upper and lower extremities and gait speed at various stages of AD. We evaluated handgrip and knee extension strength, muscle mass, and gait speed in 285 elderly outpatients with probable AD (mean age 82. 0 ± 5.3 years), including early AD (n = 82), mild AD (n = 90), and moderate AD (n = 113), and 67 elderly outpatients with normal cognition (NC) (mean age 81.1 ± 4.7 years). Sarcopenia was defined according to the consensus of the Asian Working Group for Sarcopenia. The prevalence rate of sarcopenia was significantly higher in early AD, mild AD, and moderate AD than in NC (11% in NC, 36% in early AD, 45% in mild AD, and 60% in moderate AD of the female group, and 13% in NC, 41% in early AD, 47% in mild AD, and 47% in moderate AD of the male group). Age, body mass index, and Mini-mental state examination score were associated with sarcopenia in female or male AD groups. Decreased muscle strength without loss of muscle mass of the upper and lower extremities in the female AD group and those of the lower extremity in the AD male group were found in early and mild stages. Both muscle strength and mass decreased in the moderate AD. Low gait speed was also found in the early female and male AD which progressed with advancing dementia. Subjects with AD, even the early stages of AD, showed a high prevalence rate of sarcopenia. Higher age, lower BMI, and lower MMSE score were associated with sarcopenia in the female or male AD. There were differences in muscle functions and physical performance between the stages of the female and male AD.

Role of Neuroimaging as a Biomarker for Neurodegenerative Diseases.

It has recently been recognized that neurodegenerative diseases are caused by common cellular and molecular mechanisms including protein aggregation and inclusion body formation. Each type of neurodegenerative disease is characterized by the specific protein that aggregates. In these days, the pathway involved in protein aggregation has been elucidated. These are leading to approaches toward disease-modifying therapies. Neurodegenerative diseases are fundamentally diagnosed pathologically. Therefore, autopsy is essential for a definitive diagnosis of a neurodegenerative disease. However, recently, the development of various molecular brain imaging techniques have enabled pathological changes in the brain to be inferred even without autopsy. Some molecular imaging techniques are described as biomarker in diagnostic criteria of neurodegenerative disease. Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), positron emission tomography (PET), and amyloid imaging are described in the diagnostic guidelines for Alzheimer's disease in the National Institute on Aging-Alzheimer's Association. MRI, dopamine transporter (DAT) imaging, and 123I-metaiodobenzyl-guanidine (MIBG) myocardial scintigraphy listed in the guidelines for consensus clinical diagnostic criteria for dementia with Lewy bodies are described as potential biomarkers. The Movement Disorder Society Progressive Supranuclear Palsy Study Group defined MRI, SPECT/PET, DAT imaging, and tau imaging as biomarkers. Other diagnostic criteria for neurodegenerative disease described neuroimaging findings as only characteristic finding, not as biomarker. In this review, we describe the role of neuroimaging as a potential biomarker for neurodegenerative diseases.

Comparison of diagnostic utility of semi-quantitative analysis for DAT-SPECT for distinguishing DLB from AD.

PURPOSE: It is widely known that there is low striatal 123I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). However, a consistent quantitative evaluation method for DAT-SPECT has not yet been established. There are two semi-quantitative software packages for DAT-SPECT available in Japan, namely, DaTView and DaTQUANT. The aim of this study was to identify which of these is superior for distinguishing DLB from AD. Moreover, we aimed to identify which region of the striatum is more suitable for distinguishing DLB from AD. METHODS: Patients with Alzheimer's disease (AD) (n=95) and patients with DLB (n=133) who underwent DAT-SPECT were enrolled. DaTView and DaTQUANT were used as semi-quantitative analysis tools for DAT-SPECT. RESULTS: There were significant correlations in DAT uptake between DaTView and entire regions by DaTQUANT. There was no significant difference in diagnostic accuracy between DaTView and DaTQUANT except in the posterior putamen by DaTQUANT. CONCLUSIONS: For distinguishing DLB from AD, both of DaTView and DaTQUANT software are useful. Moreover, assessing the DAT uptake in entire striatum by DaTView might be sufficient for distinguishing DLB from AD.

Correlation between clinical symptoms and striatal DAT uptake in patients with DLB.

OBJECTIVE: It is widely known that there is low striatal 123I-FP-CIT dopamine transporter-single photon emission tomography (DAT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). We assessed the correlation between symptom and regional low DAT uptake in the striatum. METHODS: Patients with Alzheimer's disease (AD) (n = 95) and patients with DLB (n = 133) who underwent DAT-SPECT were enrolled. We examined the correlation between symptoms [cognitive function decline, fluctuations, visual hallucinations, parkinsonism, and REM sleep behavior disorder (RBD)] and regional striatal DAT uptake in the patients with DLB. RESULTS: When comparing the DLB patients with or without fluctuations, visual hallucinations, or RBD, there were no significant differences in DAT uptake in any regions of the striatum. DLB patients with parkinsonism had significantly lower DAT uptake in entire striatum, entire putamen, and anterior putamen compared to DLB patients without parkinsonism. Moreover, there was weak but significant correlation between severity of parkinsonism and DAT uptake in entire regions of the striatum in patients with DLB. There was no significant correlation between cognitive function and DAT uptake in any regions of the striatum in patients with DLB. CONCLUSIONS: In patients with DLB, only parkinsonism is associated with a reduction in striatal DAT uptake.

Decreased Muscle Strength and Quality in Diabetes-Related Dementia.

BACKGROUND/AIMS: Diabetes-related dementia (DrD), a dementia subgroup associated with specific diabetes mellitus (DM)-related metabolic abnormalities, is clinically and pathophysiologically different from Alzheimer disease (AD) and vascular dementia. We determined whether skeletal muscle strength, quality, and mass decrease in individuals with DrD. METHODS: We evaluated grip and knee extension strength, muscle mass, and gait speed in 106 patients with probable AD and without type 2 DM (AD[-DM] group), 74 patients with probable AD and with DM (AD[+DM] group), and 36 patients with DrD (DrD group). Muscle quality was defined as the ratio of muscle strength to muscle mass. RESULTS: Both female and male subjects with DrD showed significantly decreased muscle strength and quality in the upper extremities compared with the subjects with AD[-DM] or AD[+DM]. Female subjects with DrD showed significantly decreased muscle quality in the lower extremities compared with the subjects with AD[-DM]. Both female and male subjects with DrD had a significantly lower gait speed compared with the subjects with AD[-DM]. However, there were no significant differences in muscle mass and the prevalence of sarcopenia between the groups. CONCLUSION: Subjects with DrD showed decreased muscle strength and quality, but not muscle mass, and had a low gait speed.