Early-onset Alzheimer Disease Associated With Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system. Although recent reports have noted that cognitive impairment is common in NMOSD, little longitudinal information is available on the trajectories of cognitive function in the disease. Here, we report a case of a 55-year-old woman with an 11-year history of NMOSD who visited our memory clinic for progressive memory loss. She was diagnosed with early-onset Alzheimer disease based on amyloid and tau positron emission tomography imaging biomarkers. This is the first report of early-onset Alzheimer disease in a patient with NMOSD. Complications of Alzheimer disease should be considered when patients with NMOSD exhibit rapid cognitive decline. More longitudinal studies of NMOSD with cognitive impairment are needed.

Combined use of the Clinical Frailty Scale and laboratory tests in acutely hospitalized older patients.

AIMS: To evaluate the Clinical Frailty Scale (CFS) and a Frailty Index based on laboratory tests (FI-lab) in terms of what each assesses about frailty and to determine the appropriateness of combined use of these two frailty scales. METHODS: This was a prospective observational cohort study in an acute geriatric ward of a university hospital. The FI-lab is the proportion of laboratory parameters that yield abnormal results from a total of 23. The FI-lab and CFS were assessed at admission. Data on activities of daily living (ADL), cognition, geriatric syndromes, and comorbidities were also collected. Main outcomes were in-hospital mortality and 90-day mortality after admission. RESULTS: In total, 378 inpatients (mean age 85.2 ± 5.8 years, 59.3% female) were enrolled. ADL and cognition correlated strongly with the CFS (Spearman's |r|> 0.60) but weakly with the FI-lab (|r|< 0.30). Both the CFS and FI-lab correlated weakly with geriatric syndromes and comorbidities (|r|< 0.40). The correlation between the CFS and FI-lab was also weak (r = 0.28). The CFS and FI-lab were independently associated with in-hospital mortality and 90-day mortality after admission. The Akaike information criterion was lower for models using both the CFS and FI-lab than for models using either tool alone. CONCLUSIONS: The CFS and FI-lab each reflected only some of the aspects of frailty in acutely hospitalized older patients. The model fit was better when the two frailty scales were used together to assess the mortality risk than when either was used alone.

Mild hyponatremia is associated with low skeletal muscle mass, physical function impairment, and depressive mood in the elderly.

BACKGROUND: Mild hyponatremia (serum sodium 130-135 mEq/L) is a common electrolyte disorder in the elderly. However, its association with both sarcopenia and cognitive function remains to be clarified. Therefore, here we investigated the association of mild hyponatremia with skeletal muscle mass, physical function, and cognitive function in the elderly. METHODS: We enrolled 75 participants with mild hyponatremia and 2907 with normonatremia (serum sodium, 136-145 mEq/L) aged ≥70 years who visited the Memory Disorder Outpatient Center of Japan's National Center for Geriatrics and Gerontology. Skeletal muscle mass index (SMI), grip strength (GS), walking speed (WS), one-leg standing (OLS) test times, and neuropsychological test scores were determined. RESULTS: One-way analysis of covariance showed that elderly participants with mild hyponatremia had lower SMI (7.1 ± 0.2, 7.2 ± 0.2 kg/m2, p = 0.04), weaker GS (19.1 ± 1.9 vs 21.4 ± 1.8 kg, p = 0.01), slower WS (0.9 ± 0.1 vs 1.1 ± 0.1 m/s, p = 0.001), and higher GDS- 15 score (6.4 ± 0.9 vs 5.2 ± 0.9, p = 0.002) than those with normonatremia. Multiple logistic regression analysis indicated that mild hyponatremia was independently associated with sarcopenia (odds ratio [OR]: 2.2, p = 0.02), slower WS (OR: 5.3, p = 0.04) and shorter OLS time (OR: 2.5, p = 0.02) as well as with severe depressive mood (OR: 2.6 p = 0.006) but not with SMI (OR: 1.6, p = 0.2) or GS (OR: 1.9, p = 0.09). CONCLUSIONS: Our results suggest that elderly people with even mild hyponatremia had physical function impairment and depressive mood.

Relationship between cognitive function and phase angle measured with a bioelectrical impedance system.

PURPOSE: The purpose of this study was to investigate the relationship between cognitive function and phase angle (PhA), an indicator of muscle quality. METHODS: This cross-sectional study enrolled outpatients who visited a memory clinic at the Nagoya University hospital from January 2016 to June 2022. We enrolled 153 participants with body composition measurements. Inclusion criteria were a Mini-Mental State Examination score of 20-30 and a clinical diagnosis of Alzheimer's dementia (AD) or amnesic mild cognitive impairment (aMCI). The background characteristics of the participants were compared according to AD and aMCI. Next, linear regression analysis was performed with PhA as the objective variable. In addition, logistic regression analysis was performed for AD diagnosis. RESULTS: PhA was lower in the AD group (P = 0.009). In linear regression analysis, PhA consistently decreased with worsening ADAS score. In logistic regression analysis, high PhA was associated with absence of AD. Gender-specific analyses showed these associations existed only in men. CONCLUSIONS: Our study of patients with AD and aMCI found that PhA decreased with worsening of cognitive function. Compared with aMCI, AD was associated with significantly lower PhA. Our results strengthen the limited evidence in the literature showing that low muscle quality is associated with poor cognitive function.

Frailty Index Based on Common Laboratory Tests for Patients Starting Home-Based Medical Care.

OBJECTIVES: To determine whether a Frailty Index based on laboratory tests (FI-lab) is associated with clinical outcomes independently of a standard nonlaboratory Frailty Index (FI-clinical) in older patients starting home-based medical care. DESIGN: Secondary analysis of data from a multicenter prospective cohort study. SETTING AND PARTICIPANTS: Patients aged ≥65 years who were starting home-based medical care services provided by doctors and nurses at Nagoya, Japan. METHODS: We calculated FI-lab (proportion of abnormal results out of 25 commonly tested laboratory parameters) and FI-clinical using 42 items based on data obtained at enrollment. The primary outcome was mortality within 2 years after starting home-based medical care. A sensitivity analysis was also conducted with 1-year mortality as the outcome. Other outcomes included hospitalization and nursing home admission within 2 years. RESULTS: In total, 188 patients (mean age 79.9 ± 10.2 years, 57.5% male) were included. The median FI-lab was 0.40 [interquartile range (IQR) 0.29-0.50] and the median FI-clinical was 0.32 (IQR 0.24-0.43). Sixty-nine patients (36.7%) died within 2 years of starting home-based medical care. A Cox proportional hazards regression analysis including age, sex, FI-lab, and FI-clinical as independent variables revealed that FI-lab was associated with 2-year mortality independently of FI-clinical [FI-lab per 0.1 unit, odds ratio (OR) 1.49, 95% CI 1.25-1.77; FI-clinical per 0.1 unit, OR 1.13, 95% CI 0.90-1.41]. The sensitivity analysis showed similar results for 1-year mortality. Neither FI-lab nor FI-clinical was associated with hospitalization or nursing home admission within 2 years. CONCLUSIONS AND IMPLICATIONS: FI-lab was associated with 2-year mortality in patients starting home-based medical care, independently of FI-clinical, and may be useful for risk assessment in this population. Studies with larger sample sizes are needed.

Association of marital relationship with quality of life among older adults with mild cognitive impairment and mild dementia.

The marital relationship is associated with the quality of life among those with cognitive impairment, but sarcopenia status seems to play an important role in the association.

Dual Sensory Impairment Predicts an Increased Risk of Postdischarge Falls in Older Patients.

OBJECTIVES: The purpose of this study was to determine the associations of vision impairment, hearing impairment, and comorbid vision and hearing impairment [ie, dual sensory impairment (DSI)] on admission to hospital with falls within 3 months of discharge in older patients. DESIGN: This prospective multicenter study included patients admitted to and discharged from geriatric wards at 3 university hospitals and 1 national medical center in Japan between October 2019 and July 2023. SETTING AND PARTICIPANTS: Of 1848 individuals enrolled during the study period, 1141 were excluded, leaving 707 for inclusion in the analysis. METHODS: Participants' background factors were compared in terms of whether they had a fall during the 3 months postdischarge. Logistic regression analysis was then performed using the presence or absence of falls after discharge as the objective variable. Three models were created using vision impairment, hearing impairment, and DSI as covariates. Other covariates included physical function, cognitive function, and depression. In addition, logistic regression analysis was performed with falls during hospitalization as the objective variable. RESULTS: DSI was significantly more common in the falls group (P = .004). Logistic regression analysis showed that the risk of falls after discharge was higher in patients with DSI (odds ratio 3.432, P = .006) than in those with vision or hearing impairment alone. When adjusted for physical function, cognitive function, depression, and discharge location, DSI was significantly associated with an increased risk of falls after discharge (odds ratio 3.107, P = .021). The association between DSI and falls during hospitalization did not reach statistical significance, but a trend was observed. CONCLUSIONS AND IMPLICATIONS: This study is the first to show an association between DSI and falls after discharge. Simple interventions for patients with DSI may be effective in preventing falls, and we suggest that they be actively implemented early during hospitalization.

Objective physical function declines in the absence of subjective physical complaints among patients with amnestic mild cognitive impairments and mild alzheimer's disease.

PURPOSE: To examine the extent to which patients with amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD) perceive their own physical decline. METHODS: This study included 4450 outpatients (1008 normal cognition [NC], 1605 aMCI, and 1837 mild AD) who attended an initial visit to a memory clinic between July 2010 and June 2021. Their physical function was assessed by the Timed Up and Go test, one-leg standing test, and grip strength. For physical complaints, data were obtained on reports of fear of falling and dizziness or staggering. Logistic regression analysis was performed to compare the patients' physical function and complaints for each stage of NC, aMCI, and mild AD. RESULTS: Objective physical function declined from aMCI and the mild AD stage, but subjective physical complaints decreased by 20-50% in aMCI and 40-60% in mild AD compared with the NC group. CONCLUSION: As objective physical functional declined from the aMCI stage onward, subjective physical complaints decreased. This suggests a need for objective assessment of physical function in aMCI and mild AD patients even when they have no physical complaints in the clinical setting.

Dehydration and hospital-associated disability in acute hospitalized older adults.

PURPOSE: Dehydration is highly prevalent in hospitalized older adults and has been linked to poor outcomes. It is considered a modifiable factor, so early identification and intervention may avoid adverse events and improve quality of life after discharge. Hospital-associated disability (HAD) is known to be a poor prognostic factor and can be categorized into mobility impairment and self-care impairment in setting goals for management. Few studies have directly examined the association between dehydration and HAD and therefore here we examined whether dehydration is a predictor of HAD categorized into mobility and self-care impairment among acute hospitalized older adults. METHODS: Patients aged 65 years or older who were admitted to the geriatric ward of an acute hospital were recruited for this prospective cohort study. Estimated serum osmolarity > 300 mOsm/kg was defined as current dehydration. HAD was assessed between baseline and discharge and at 3 months after discharge, and was evaluated separately for mobility and self-care impairments. RESULTS: In total, 192 patients (mean age, 84.7 years; male, 41.1%; dehydration, 31.3%) were analyzed. The occurrence of HAD was significantly higher in the dehydrated group than in the non-dehydrated group (42.4% vs 26.5%) from baseline to 3 months after discharge. In multiple logistic regression analysis, dehydration was significantly associated with HAD in self-care from baseline to 3 months after discharge (odds ratio, 2.25; 95% confidence interval, 1.03-4.94). CONCLUSIONS: Dehydration could predict the occurrence of HAD in acute hospitalized older adults. A multifaceted approach may be necessary to improve the management of dehydration in these patients.

Intrinsic capacity in acutely hospitalized older adults.

OBJECTIVES: We aimed to examine the association between intrinsic capacity (IC) and adverse outcomes of hospitalization. DESIGN: A prospective observational cohort study. SETTING AND PARTICIPANTS: We recruited patients aged 65 years or older who were admitted to the geriatric ward of an acute hospital between Oct 2019 and Sep 2022. MEASUREMENTS: Each of the five IC domains (locomotion, cognition, vitality, sensory, and psychological capacity) was graded into three levels, and the composite IC score was calculated (0, lowest; 10, highest). Hospital-related outcomes were defined as in-hospital death, hospital-associated complications (HACs), length of hospital stay, and frequency of discharge to home. RESULTS: In total, 296 individuals (mean age 84.7 ± 5.4 years, 42.7 % males) were analyzed. Mean composite IC score was 6.5 ± 1.8, and 95.6 % of participants had impairment in at least one IC domain. A higher composite IC score was independently associated with lower frequency of in-hospital death (odds ratio [OR] 0.59) and HACs (OR 0.71), higher frequency of discharge to home (OR 1.50), and shorter length of hospital stay (ß = -0.24, p < 0.01). The locomotion, cognition, and psychological domains were independently associated with the occurrence of HACs, discharge destination, and length of hospital stay. CONCLUSION: Evaluating IC was feasible in the hospital setting and was associated with outcomes of hospitalization. For older inpatients with decreased IC, integrated management may be required to achieve functional independence.

Relationship Between Non-Cognitive Intrinsic Capacity and Activities of Daily Living According to Alzheimer's Disease Stage.

BACKGROUND: Few studies have examined the relationship between non-cognitive factors and activities of daily living (ADL) according to Alzheimer's disease (AD) stage. OBJECTIVE: We aimed to identify the differences in non-cognitive factors according to AD stages and their involvement in basic and instrumental ADL performance by using intrinsic capacity (IC) in groups with cognition ranging from normal to moderate or severe AD. METHODS: We enrolled 6397 patients aged≥65 years who visited our memory clinic. Non-cognitive IC was assessed using the locomotion, sensory, vitality, and psychological domains. Multiple logistic regression was performed to identify how non-cognitive IC declines over the AD course and examine the correlation between non-cognitive IC and basic and instrumental ADL performance. RESULTS: Non-cognitive IC declined from the initial AD stage and was significantly correlated with both basic and instrumental ADL performance from the aMCI stage through all AD stages. In particular, the relationship between IC and basic ADL was stronger in mild and moderate to severe AD than in the aMCI stage. On the other hand, the relationship between IC and instrumental ADL was stronger in aMCI than in later AD stages. CONCLUSIONS: The results show non-cognitive factors, which decline from the aMCI stage, are correlated with ADL performance from the aMCI stage to almost all AD stages. Considering that the relationship strength varied by ADL type and AD stage, an approach tailored to ADL type and AD stage targeting multiple risk factors is likely needed for effectively preventing ADL performance declines.

Older adults with a higher frailty index tend to have electrolyte imbalances.

OBJECTIVES: Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor. We hypothesized that frail older adults would tend to have electrolyte imbalances because they should have many stressors together with fragile physiological systems. In this study, we aimed to determine whether older adults with higher Frailty Index scores have electrolyte imbalances and to establish which domains of the Frailty Index are correlated with electrolyte imbalances. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A total of 4204 older adults aged 70 years or over who visited the Japanese National Center for Geriatrics and Gerontology. METHODS: We calculated the 50-item Frailty Index with the following domains: comorbidities, cognitive function and mood, basic and instrumental activities of daily living, physical function, nutrition, and fall risks from physical weakness and comorbidities. Participants were categorized into four groups: a non-frail group (Frailty Index ≤0.2), mildly frail group (0.20 < Frailty Index ≤0.3), moderately frail group (0.3 < Frailty Index ≤0.4), and severely frail group (0.4 < Frailty Index). Their serum sodium, potassium, calcium, and phosphorus concentrations were measured. A multiple regression model was used to explore the relationship of electrolyte imbalances with the Frailty Index and to determine which frailty domains are correlated with electrolyte imbalances. RESULTS: Compared with the non-frail group, the mildly and moderately frail groups tended to have hypernatremia and hypophosphatemia, whereas the severely frail group tended to have dysnatremia, hypokalemia, and hypophosphatemia. The estimated odds ratios increased by 15%-52% for each electrolyte imbalance as the Frailty Index increased by 0.1. The Frailty Index domains of cognitive function, activities of daily living, and nutrition were correlated with more than three kinds of electrolyte imbalances, the domains of physical function and fall risks from physical weakness were correlated with three kinds of electrolyte imbalances, and the domains of comorbidities and fall risks from comorbidities were correlated with two kinds of electrolyte imbalances. CONCLUSIONS: Older adults with higher Frailty Index scores tend to have electrolyte imbalances.

Associations Between Polypharmacy and Gait Speed According to Cognitive Impairment Status: Cross-Sectional Study in a Japanese Memory Clinic.

BACKGROUND: Polypharmacy, usually defined as the use of 5 or more drugs, is associated with reduced quality of life, adverse events, and frailty. Slow gait speed is a component of physical frailty, and some studies have suggested an association between polypharmacy and slow gait speed. OBJECTIVE: We aimed to determine the effects of polypharmacy on the gait difference according to stages of cognitive decline in a cross-sectional study of memory clinic patients. METHODS: Participants were 431 outpatients aged 65 year or older who were cognitively normal (CN) or had mild cognitive impairment (MCI) or dementia due to Alzheimer's disease. Participants were divided into a polypharmacy group and a non-polypharmacy group in each group. Multiple regression analysis and logistic analysis were used for data analysis. RESULTS: There were 182 patients in the polypharmacy group and 249 patients in the non-polypharmacy group. Multiple regression analysis revealed that gait speed had significant negative associations with number of medications and polypharmacy status in the CN group (ß: -0.026 [-0.041 to -0.0018] and -0.128 [-0.022 to -0.0033], respectively) and MCI group (-0.018 [-0.028 to -0.0009] and -0.100 [-0.166 to -0.0034]). Logistic regression analysis also showed that number of medications was associated with slow gait status (< 1 m/s) in the CN group (OR: 1.336 [1.115 to 1.601]) and MCI group (1.128 [1.022 to 1.244]). CONCLUSION: CN and MCI patients with polypharmacy have slower gait speed. Attention should be paid to decreased gait speed in older adults with polypharmacy even when their cognitive function is relatively preserved.

Cross-Sectional Examination of Homocysteine Levels with Sarcopenia and Its Components in Memory Clinic Outpatients.

BACKGROUND: Homocysteine is a common risk factor for cognitive impairment and sarcopenia. However, very few studies have shown an association between sarcopenia and serum homocysteine levels after adjustment for cognitive function. OBJECTIVE: The purpose of this study was to investigate the relationship between homocysteine and sarcopenia in memory clinic patients. METHODS: This cross-sectional study investigated outpatients in a memory clinic. We enrolled 1,774 participants (≥65 years old) with measured skeletal muscle mass index (SMI), hand grip strength (HGS), and homocysteine. All participants had undergone cognitive assessments and were diagnosed with dementia, mild cognitive impairment, or normal cognition. Patient characteristics were compared according to sarcopenia presence, SMI level, or HGS. Multivariate logistic regression analysis was performed to determine the association of homocysteine with sarcopenia, low SMI, or low HGS. Next, linear regression analysis was performed using HGS as a continuous variable. RESULTS: Logistic regression analysis showed that low HGS was significantly associated with homocysteine levels (p = 0.002), but sarcopenia and low SMI were not. In linear regression analysis, HGS was negatively associated with homocysteine levels after adjustment for Mini-Mental State Examination score (ß= -2.790, p < 0.001) or clinical diagnosis of dementia (ß= -3.145, p < 0.001). These results were similar for men and women. CONCLUSION: Our results showed a negative association between homocysteine and HGS after adjustment for cognitive function. Our findings strengthen the assumed association between homocysteine and HGS. Further research is needed to determine whether lower homocysteine levels lead to prevent muscle weakness.

Polypharmacy and gait speed in individuals with mild cognitive impairment.

AIM: Polypharmacy has been reported to be associated with poor outcomes, including falls and frailty, in older populations. Past studies have found that slower walking speed is a good predictor of progression to frank dementia in mild cognitive impairment (MCI). Some studies of the general population reported that polypharmacy was associated with slower gait speed; however, it remains to be elucidated whether polypharmacy affects gait speed even in individuals with MCI, who already have some deterioration in gait compared with cognitively preserved individuals. The current study explored the association between the number of medications and gait speed in older adults with MCI who have a Clinical Dementia Rating score of 0.5. METHODS: A total of 128 individuals with MCI were included in the present study. The participants were divided into three groups according to the number of medications they were taking: up to four medications was non-polypharmacy; five to nine medications was polypharmacy; and ≥10 medications was hyperpolypharmacy. The background characteristics were compared by analysis of variance for numerical numbers, and by χ2 analysis for categorical factors. Multiple regression and logistic analysis were applied to investigate the association between gait speed and polypharmacy status or number of medications. RESULTS: Gait speed was significantly negatively associated with hyperpolypharmacy status and the number of medications. Slow gait speed (<1 m/s) was also significantly associated with polypharmacy status and the number of medications. CONCLUSIONS: We found that polypharmacy was associated with slow gait speed in older adults with MCI. Geriatr Gerontol Int 2019; 19: 730-735.

Physical Function Differences Between the Stages From Normal Cognition to Moderate Alzheimer Disease.

OBJECTIVES: We investigated the differences in the physical function test results across stages from normal cognition (NC) to moderate Alzheimer disease (AD) and how risk factors of physical function decline are correlated with the physical function test results. DESIGN: A cross-sectional study of outpatients at the Memory Disorder Outpatient Center of Japan's National Center of Geriatrics and Gerontology. PARTICIPANTS: We enrolled 882 individuals aged ≥65 diagnosed with NC (n = 210), amnestic mild cognitive impairment (aMCI; n = 273), mild AD (n = 181) or moderate AD (n = 197). MEASUREMENTS: We measured the participants' results for functional reach (FR), the one-leg standing (OLS) test, the Timed Up and Go (TUG) test, tandem gait (TG), and grip strength (GS). A one-way analysis of covariance (ANCOVA) was used to identify significant differences among the groups' results on the physical function tests, controlling for age, sex, educational year, Mini-Nutritional Assessment, senior activity and exercise frequency, low-density lipoprotein, body mass index, free-fat mass index, and assistance for the TUG test. Multiple regression analysis was also used to investigate the correlation between these covariates and physical function tests results. RESULTS: The ANCOVA showed that FR, OLS, and TG were significantly worse among the individuals with aMCI, mild AD, or moderate AD compared with NC. However, TUG was significantly worse only in the moderate AD group compared with the NC, aMCI, and mild AD group. Multiple regression analysis showed that aging was correlated with poorer scores on all physical function tests, women had poorer scores on FR and GS than men, and low frequency of senior activity was significantly correlated with poorer scores on FR, OLS, and TG. CONCLUSION: Postural impairment and instability on TG was seen in earlier AD stages compared with instability on TUG. As were the covariates of age and sex, senior activity frequency was significantly related to 2 or more physical function tests.