Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort.

The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice.

Bidirectional associations of high-level cognitive domains with hand motor function and gait speed in high-functioning older adults: A 7-year study.

BACKGROUND: Whether age-related decline in the musculoskeletal system may contribute to a decline in cognitive performance or vice versa is unclear. Understanding the direction of their associations and the extent to which upper and lower extremities similarly predict subtle changes in high-level cognitive performance will help elucidate their mechanisms, especially that of the hand dexterity. METHODS: We evaluated the bidirectional associations of motor performance and high-level cognitive domains in 165 highly cognitively and physically healthy older adults. Motor performance tests consisted of handgrip strength, hand dexterity, assessed with the Purdue Pegboard Test (PPT), and usual and maximum gait speeds. High-level cognitive measures included executive function and information processing speed. The Trail Making Test (TMT)B and the letter and category fluency tests (LFT and CFT) evaluated executive function, while the TMTA and Digit Symbol assessed processing speed. Measurements were taken at baseline and at 2-, 5- and 7-year follow-up. RESULTS: Generalized linear mixed-effect models showed that baseline hand dexterity and its trajectory predicted changes in TMTB, CFT, TMTA, and Digit Symbol over time, and vice versa. Baseline maximum gait speed was associated with LFT over time and vice versa. No associations were found for handgrip and usual gait speed. CONCLUSION: The positive bidirectional association observed both in hand dexterity and maximum gait speed with executive function performance and that of hand dexterity with processing speed over time highlights a reciprocal relationship where each factor affects the other and both factors are dependent on each other, suggesting commonality in their neural basis.

Population-based reference values for tongue pressure in Japanese older adults: A pooled analysis of over 5,000 participants.

PURPOSE: To establish age- and sex-specific population reference values for tongue pressure (TP) in community-dwelling Japanese older adults. METHODS: For this analysis, we pooled four population-based studies on community-dwelling adults aged ≥65 years that measured TP using a JMS tongue pressure measuring device. We calculated the means and deciles of TP per 5-year age group for each sex. We also estimated age trends in TP for men and women. RESULTS: In total, 5,083 individuals (2,150 men and 2,933 women, with a mean [standard deviation] age of 75.2 [6.5] years) were included in the present analysis. In male participants, the mean (standard deviation) TPs for ages 65-69, 70-74, 75-79, 80-84, and ≥85 years were 34.0 (8.4), 32.2 (8.1), 30.8 (8.3), 28.4 (8.9), and 24.4 (8.2) kPa, respectively. In female participants, the corresponding values were 31.5 (7.1), 30.5 (7.5), 29.6 (7.3), 28.4 (8.0), and 26.4 (7.6) kPa, respectively. For both sexes, there were significant declining trends in TP with advanced age. In addition, the interaction between age and sex had a significant effect on TP (regression coefficient [95% confidence interval] = -0.18 [-0.25 to -0.11] when age was modeled as a continuous variable and sex was modeled as a categorical variable [coded as 0=women, 1=men]). CONCLUSIONS: This study determined age- and sex-specific reference values for TP, presented as means and deciles, in community-dwelling Japanese older adults aged ≥65 years. This study also demonstrated sex differences in age-related declines in TP.

Normative Data of the Trail Making Test Among Urban Community-Dwelling Older Adults in Japan.

Introduction: Population aging is likely to increase the number of people with dementia living in urban areas. The Trail Making Test (TMT) is widely used as a cognitive task to measure attention and executive function among older adults. Normative data from a sample of community-dwelling older adults are required to evaluate the executive function of this population. The purpose of this study was to examine the Trail Making Test completion rate and completion time among urban community-dwelling older adults in Japan. Methods: A survey was conducted at a local venue or during a home visit (n = 1,966). Cognitive tests were conducted as a part of the survey, and TMT Parts A (TMT-A) and B (TMT-B) were completed after the completion of the Japanese version of the Mini-Mental State Examination (MMSE-J). Testers recorded TMT completion status, completion time, and the number of errors observed. Results: In the TMT-A, 1,913 (99.5%) participants understood the instructions, and 1,904 (99.1%) participants completed the task within the time limit of 240 s. In the TMT-B, 1,839 (95.9%) participants understood the instructions, and 1,584 (82.6%) participants completed the task within the time limit of 300 s. The completion rate of TMT-B was 90.2 and 41.8% for participants with an MMSE-J score of >23 points and ≦23 points, respectively. Results of multiple regression analyses showed that age, education, and the MMSE-J score were associated with completion time in both TMTs. Conclusion: In both TMTs, completion time was associated with age, education, and general cognitive function. However, not all participants completed the TMT-B, and the completion rate was relatively low among participants with low MMSE-J scores. These findings may help interpret future TMT assessments.

Promoting cultural change towards dementia friendly communities: a multi-level intervention in Japan.

BACKGROUND: Effective strategies to develop dementia-friendly communities (DFCs) are needed in aging societies. We aimed to propose a strategy to develop DFCs from a Japanese perspective and to evaluate an intervention program that adopted the strategy. METHODS: This study implemented a multi-level intervention that emphasized nurturing community social capital in a large apartment complex in the Tokyo metropolitan area in 2017. We offered an inclusive café that was open for extended hours as a place to socialize and a center for activities that included monthly public lectures. Individual consultation on daily life issues was also available for free at the café. Postal surveys were sent out to all older residents aged 70 years and older in 2016 and 2019. With a one-group pre-test and post-test design, we assessed changes in the proportion of older residents who had social interaction with friends and those who were confident about living in the community, even if they were living with dementia. RESULTS: Totals of 2633 and 2696 residents completed the pre and post-intervention surveys, respectively. The mean age of the pre-intervention respondents was 77.4 years; 45.7% lived alone and 7.7% reported living with impaired cognitive function. The proportion of men who had regular social interaction and were confident about living in their community with dementia increased significantly from 38.8 to 44.5% (p = 0.0080) and from 34.1 to 38.3% (p = 0.045), respectively. Similar significant increases were observed in the subgroup of men living with impaired cognitive function, but not in the same subgroup for women. CONCLUSIONS: The intervention benefitted male residents who were less likely to be involved in the community's web of social networks at baseline. A strategy to create DFCs that emphasizes nurturing community social capital can form a foundation for DFCs. TRIAL REGISTRATION: This study was retrospectively registered in the University hospital Medical Information Network (UMIN) Clinical Trial Registry (registry number: UMIN000038193 , date of registration: Oct 3, 2019).

Olfactory function and discrimination ability in the elderly: a pilot study.

We recently reported that subjects with a higher olfactory identification threshold for rose odor declined more in attentional ability in the elderly. This study focuses on discrimination ability and olfactory identification threshold in twelve elderly subjects living in a community (age: 80.9 ± 1.6). Olfactory function was assessed by the rose odor identification threshold. We assessed the discrimination ability by distinguishing 5 similar odor pairs. Our results showed that the subjects with a higher olfactory identification threshold (≥ 5) declined more in discrimination ability (14% ± 14%, p = 0.03) compared to those with a lower threshold (≤ 4) (averaged value set at 100%). As discrimination ability is related to the basal forebrain cholinergic system, our results suggest that olfactory impairment links to the decline in cognitive function relating the cholinergic system.

[Comprehensive health assessment of community-dwelling older people using mail method and its association with future transition to need for long-term care and dementia].

Objectives　We selected assessment items that can be used to evaluate the physical, mental, and social functions of community-dwelling older people comprehensively and easily, and examined whether these items could predict a future transition to the requirement for nursing care and dementia.Methods　We conducted a self-administered mail survey of 4,439 community-dwelling older people, who were not certified as requiring nursing care in 2011. The items for the survey were shortlisted out of a total of 54 items that were selected by referring to existing scales, and the evaluation items were determined by pass rate and factor analysis. The cut-off point of the total scores was estimated by ROC analysis using the certification of requiring long-term care (support level 1 or higher) and level of independence in the daily lives of older people with dementia (independence level I or higher) in 2014 as external criteria. The predictive validity was examined by binomial logistic regression analysis using the cut-off point of the total score and the score of the sub-domains as explanatory variables, and the requirement of nursing care and independence level of dementia in 2014 as objective variables.Results　A factor analysis of 1,810 subjects with no deficiencies in the 54 items identified 24 items in five domains (mental health, walking function, Instrumental Activities of Daily Living (IADL), cognitive function, and social support). During the ROC analysis, the cut-off point of the total score was estimated to be 20/21 points (nursing care: AUC 0.75, sensitivity 0.77, specificity, 0.56; dementia: AUC 0.75; sensitivity 0.79, specificity 0.55). The binomial logistic regression analysis showed that persons with a total score of less than 20 points in 2011 were significantly more likely to be certified as requiring nursing care (odds ratio 2.57, 95%CI 1.69-3.92, P<0.01) or show a decline in their independence level of dementia (odds ratio 3.12, 95%CI 1.83-5.32, P<0.01) in 2014. The scores of mental health, walking function, and IADL were significantly associated with certification of requiring nursing care, while walking function and cognitive function were significantly associated with dementia.Conclusion　We believe that the selected items in this study can successfully predict a transition to needing nursing care and dementia in the future. In the sub-domains, the results suggested an association with physical and mental function, as has been previously reported, but little association with social function.

Cognitive function, daily function and physical and mental health in older adults: A comparison of venue and home-visit community surveys in Metropolitan Tokyo.

PURPOSE: We conducted surveys in older people at a venue and in home-visits, and compared cognitive and health status between the two groups to assess their cognitive and everyday functioning. METHODS: Among 7,614 persons aged 70 years and older living in an urban area, 5,430 responded to a mail survey for sociodemographic characteristics and self-rated questionnaires including the Geriatric Depression Scale-short form (GDS-15). Of these, 1,360 agreed to attend a venue survey, and 693 agreed to take a home-visit survey. Trained nurses examined participants' blood pressure, medical history, and daily functions using the dementia assessment sheet for community-based integrated care system (DASC-21), and tested their cognitive function using the Mini-Mental State Examination (MMSE). RESULTS: Of 2,053 participants, 2,020 (venue: 1,352; home-visit: 668) completed the MMSE. Median MMSE scores for the venue and home-visit groups were 28 and 26 points, respectively, with 130/1,352 (9.6%) and 205/668 (30.7%) participants below the traditional 23/24 cutoff score. The home-visit group had lower mobility, lower frequency of going out, poorer mental health, and lower independence in instrumental daily activities. Notably, 39.9% and 43.7% of the venue and home-visit groups lived alone, respectively. CONCLUSIONS: In this sample of urban older people, the rate of cognitive decline detected using the MMSE was three times higher in the home-visit group than in the venue group. Home-visit participants were more likely to have difficulty in physical, cognitive, and everyday functioning, suggesting they have a greater need for daily living support to continue living in the community.

Depressed mood and frailty among older people in Tokyo during the COVID-19 pandemic.

BACKGROUND: The study aim was to identify depressed mood and frailty and its related factors in older people during the coronavirus disease 19 pandemic. METHODS: Since 2010, we have conducted questionnaire surveys on all older residents, who are not certified in the long-term care insurance, living in one district of Tokyo municipality. These residents are divided into two groups by birth month, that is those born between April and September and those born between October and March, and each group completes the survey every 2 years (in April and May). Study participants were older residents who were born between April and September and who completed the survey in spring 2018 and in spring 2020, the pandemic period. Depressed mood and frailty were assessed using the Kihon Checklist, which is widely used by local governments in Japan. We had no control group in this study. RESULTS: A total of 1736 residents responded to both surveys. From 2018 to 2020, the depressed mood rate increased from 29% to 38%, and frailty increased from 10% to 16%. The incidence of depressed mood and frailty was 25% and 11%, respectively. Incidence of depressed mood was related to subjective memory impairment and difficulty in device usage, and incidence of frailty was related to being older, subjective memory impairment, lack of emotional social support, poor subjective health, and social participation difficulties. CONCLUSIONS: Older people with subjective memory impairment may be a high-risk group during the coronavirus pandemic. Telephone outreach for frail older people could be an effective solution. We recommend extending the scope of the 'reasonable accommodation' concept beyond disability and including older people to build an age-friendly and crisis-resistant community.

The relationship between olfaction and cognitive function in the elderly.

This study investigated the relationship between olfaction and cognitive function in 12 elderly people (age: 80.9 ± 1.6) living in the community. Olfactory function was assessed by the identification threshold for rose odor. Four cognitive measures consisting general cognitive ability assessed by Mini-Mental State Examination (MMSE), its sub-domains, and attentional ability assessed by drawing a line to connect the numbers consecutively (trail-making test part A; TMT-A), were assessed. Subjects with a higher olfactory threshold (≥ 5) declined more in the performance speed of TMT-A (73% ± 7%, p = 0.05) compared with those subjects with a lower threshold (≤ 4) (averaged value was set at 100%). Other cognitive statuses assessed by MMSE tended to decline in subjects with higher thresholds. Because attentional function relates to the basal forebrain cholinergic system, our results suggest that olfactory impairment links to the decline in cognitive function, particularly of attention-relating cholinergic function.

Characteristics of detected and undetected dementia among community-dwelling older people in Metropolitan Tokyo.

AIM: Although a series of policies have been adapted to deliver an early diagnosis of dementia, many people living with dementia remain undetected and undiagnosed. The aim of this study is to investigate the characteristics of undetected dementia in community-dwelling older people in Metropolitan Tokyo. METHODS: We conducted a three-step survey. First, the questionnaires were mailed, in total, to 7614 residents aged ≥70 years in one area in Tokyo, and 5430 were retrieved. Secondly, 2020 individuals attended the face-to-face survey, including Mini-Mental State Exam (MMSE). Thirdly, 198 of 335 individuals who scored <24 on MMSE were visited. Diagnosis of dementia, Clinical Dementia Rating and need for social support were assessed by the interdisciplinary team at their home, and psychological variables, sociological variables and sociodemographic variables were evaluated. RESULTS: Among the 198 participants, 78 (39.4%) were assessed to have dementia. Among those who had dementia, 34 had received a previous diagnosis of dementia in a clinical setting, i.e., the rate of undetected dementia among our 198 participants was 56.4%. People living with dementia without a dementia diagnosis tended to have more complex social support needs, particularly in the domains of dementia diagnosis, medical check-ups for physical conditions, continuous medical care and housing support. In addition, they exhibited signs of frailty. CONCLUSIONS: Given that people living with dementia without a dementia diagnosis are at risk of losing housing or physical health, it is a threat to human rights. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; ••: ••-••.

Prevalence and clinical features of hearing loss caused by EYA4 variants.

Variants in the EYA4 gene are known to lead to autosomal dominant non-syndromic hereditary hearing loss, DFNA10. To date, 30 variants have been shown to be responsible for hearing loss in a diverse set of nationalities. To better understand the clinical characteristics and prevalence of DFNA10, we performed genetic screening for EYA4 mutations in a large cohort of Japanese hearing loss patients. We selected 1,336 autosomal dominant hearing loss patients among 7,408 unrelated Japanese hearing loss probands and performed targeted genome enrichment and massively parallel sequencing of 68 target genes for all patients. Clinical information of cases with mutations in EYA4 was gathered and analyzed from medical charts. Eleven novel EYA4 variants (three frameshift variants, three missense variants, two nonsense variants, one splicing variant, and two single-copy number losses) and two previously reported variants were found in 12 probands (0.90%) among the 1,336 autosomal dominant hearing loss families. The audiometric configuration of truncating variants tends to deteriorate for all frequencies, whereas that of non-truncating variants tends to show high-frequency hearing loss, suggesting a new correlation between genotype and phenotype in DFNA10. The rate of hearing loss progression caused by EYA4 variants was considered to be 0.63 dB/year, as found in this study and previous reports.

Sphenoid sinus development in patients with acquired middle ear cholesteatoma.

OBJECTIVE: In this study, we examine the relationship between developmental insufficiency of mastoid air cells and abnormal morphology of the paranasal sinuses in patients with chronic otitis media (COM) and acquired middle ear cholesteatoma (AMEC) using precise image assessment, in order to evaluate whether the anatomical features of paranasal sinuses has any impact on the pathogenesis in COM and AMEC. METHODS: A total of 127 patients, including 45 COM patients and 82 AMEC patients, were enrolled for this study. The existence of nasal septal deviation, the existence of paranasal sinus opacification, the modified Lund-Mackay score, the diameters of the paranasal sinuses, the Vidic classification, mastoid development, and cranial size were assessed by CT examination. A further 76 adult patients who underwent high-resolution CT imaging of their skull bone for other diseases were enrolled as the control. RESULTS: The AMEC group showed a significantly shorter sphenoid length (P < 0.01) and lower Vidic classification score (P < 0.01) compared to the control group in this study. In addition, we observed that patients with AMEC had less pneumatization of the mastoid air cells compared to the control individuals, and that the sphenoid length of the poor MC score group was significantly shorter than that of the good MC score group. CONCLUSION: Our results suggested that the developmental deficiency in sphenoid length caused by long-standing pediatric rhinosinusitis might indicate the potential of chronic middle ear inflammation in childhood and impact the pneumatization of mastoid air cells. Therefore, chronic rhinosinusitis during the childhood and adolescence might play a role in the pathophysiology of AMEC.

Does community social capital buffer the relationship between educational disadvantage and cognitive impairment? A multilevel analysis in Japan.

BACKGROUND: This study explored the relationship between community social capital and cognitive impairment, with a focus on the buffering role of community social capital in the association between educational disadvantage and cognitive impairment in community-dwelling older adults in Japan. METHODS: We used data from two population-based, cross-sectional surveys targeting people aged ≥65 years in a suburban city of the Tokyo metropolitan area (n = 897; 49.8% men; average age = 74.4 years). Social capital included social support (emotional and instrumental support) and the strength of social networks (neighborly ties). To create district-level social capital indicators, we aggregated individual responses on social capital within each district. The Mini-Mental State Examination, Japanese version was used for the assessment of cognitive function. RESULTS: Using multilevel logistic regression analysis, we found that lower amounts of district-level emotional and instrumental support were associated with a greater likelihood of cognitive impairment among men. For women, district-level emotional support was associated with a greater likelihood of cognitive impairment. Additionally, a strong district-level social network buffered the relationship between low education and cognitive impairment in both sexes. CONCLUSIONS: Community social capital appears to have a protective role in determining cognitive function in old age. Our findings may facilitate the development of new community-based strategies to combat dementia.

Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort.

Variants of the LOXHD1 gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8074 Japanese hearing loss patients utilizing massively parallel DNA sequencing to identify individuals with LOXHD1 variants and to assess their phenotypes. A total of 28 affected individuals and 21 LOXHD1 variants were identified, among which 13 were novel variants. A recurrent variant c.4212 + 1G > A, only reported in Japanese patients, was detected in 18 individuals. Haplotype analysis implied that this variation occurred in a mutational hot spot, and that multiple ancestors of Japanese population had this variation. Patients with LOXHD1 variations mostly showed early onset hearing loss and presented different progression rates. We speculated that the varying severities and progression rates of hearing loss are the result of environmental and/or other genetic factors. No accompanying symptoms, including vestibular dysfunction, with hearing loss were detected in this study. Few studies have reported the clinical features of LOXHD1-gene associated hearing loss, and this study is by far the largest study focused on the evaluation of this gene.

Ecological relationship between social capital and cognitive decline in Japan: A preliminary study for dementia-friendly communities.

AIM: Building community social capital is important for socially inclusive societies, leading to dementia-friendly communities. However, quantitative evidence is currently lacking regarding the effectiveness of dementia-friendly communities, including the association with community social capital. The current study examined the ecological relationship between social capital and the proportion of people with cognitive decline. METHODS: Data were obtained from population-based, cross-sectional surveys (mail-in questionnaire survey and home-interview survey) of community-dwelling older adults aged ≥65 years, living in 17 district areas in Machida City, Tokyo, Japan. Social capital included social networks (neighborly ties) and social support (emotional support and instrumental support). Cognitive function was assessed using the Mini-Mental State Examination, Japanese version (with a cut-off of 23/24). The proportions of people with high social capital and cognitive decline (Mini-Mental State Examination, Japanese version ≤23) were calculated for residential districts and used in the analysis. RESULTS: The district-level social capital indicators were positively and moderately correlated with the proportion of people with cognitive decline. After adjusting for the aging rate, educational level and population density of the district, an ordinal logistic regression analysis showed that higher proportions of people with strong neighborly ties and people with strong instrumental support were significantly associated with a higher proportion of people with cognitive decline. This trend was stronger among women than men. CONCLUSIONS: People can continue to live in communities with high social capital, even if they are experiencing cognitive decline. Although this study was preliminary, it provided empirical evidence for the benefits of promoting dementia-friendly communities. Geriatr Gerontol Int 2019; 19: 950-955.

Cognitive frailty in community-dwelling older Japanese people: Prevalence and its association with falls.

AIM: To investigate the prevalence and associated factors of cognitive frailty and cognitive frailty-related falls in community-dwelling older people. METHODS: A total of 25 out of 1192 community-dwelling older people aged >70 years with cognitive frailty participated in the present cross-sectional study. Cognitive function was assessed using the Mini-Mental State Examination. Physical function measures included calf circumference, Timed Up and Go (TUG) and usual walking speed. Interviews were carried out to assess Council on Nutrition Appetite Questionnaire (CNAQ); chronic diseases including hypertension, diabetes and falls; as well as physical frailty, defined as having three of five criteria: muscle weakness, slowness, exhaustion, low activity and weight loss. RESULTS: The prevalence of cognitive frailty was 2.1%. Participants with cognitive frailty had significantly reduced Mini-Mental State Examination and calf circumference; and higher instrumental activities of daily living disability and falls. Old age (OR 1.151, 95% CI 1.053-1.257), fall history (OR 3.577, 95% CI 1.381-9.263), having four or more chronic diseases (OR 7.419, 95% CI 2.117-26.005) and slower TUG (OR 1.234, 95% CI 1.041-1.462) were significantly associated with cognitive frailty, whereas greater calf circumference (OR 0.748, 95% CI 0.625-0.895) and CNAQ (OR 0.736, 95% CI 0.628-0.8631) had protective effects. Old age (OR 1.132, 95% CI 1.002-1.280), hospitalization (OR 10.090, 95% CI 2.554-39.854), having four or more chronic diseases (OR 5.120, 95% CI 1.113-23.557) and slower TUG (OR 1.394, 95% CI 1.167-1.665) were significantly associated with cognitive frailty-related falls, whereas CNAQ (OR 0.704, 0.571-0.868) had protective effects. CONCLUSIONS: Age, chronic disease, TUG and CNAQ were significantly associated with cognitive frailty and cognitive frailty-related falls. The TUG and CNAQ have the greatest potential for improvement by intervention or lifestyle change. Further research is necessary to determine the efficacy of positive changes in these factors for symptomatic improvements. Geriatr Gerontol Int 2019; 19: 647-653.

Correction to: Hand dexterity, not handgrip strength, is associated with executive function in Japanese community-dwelling older adults: a cross-sectional study.

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Hand dexterity, not handgrip strength, is associated with executive function in Japanese community-dwelling older adults: a cross-sectional study.

BACKGROUND: An association between handgrip strength, hand dexterity and global cognition is suggested; however, it is unclear whether both hand motor functions are associated with executive function, which is important for performing daily activities. Understanding this association will help identify motor risk factors for impairment of executive function in late adulthood. We aim to investigate the relationship of handgrip strength and hand dexterity with executive function in physically and mentally healthy community-dwelling older adults. METHODS: Three hundred and twenty-six older adults (287 women, mean age ± SD, 70.1 ± 5.6) underwent handgrip strength and hand dexterity tests using a hand dynamometer and the Purdue Pegboard Test (PPT), respectively. Executive function was evaluated with the Trail Making Test (TMT)-A, TMT-B and Digit symbol; global cognition was assessed with the Mini-Mental State Examination (MMSE). RESULTS: Age-group differences showed that the younger groups (60-64, 65-69 and 70-74) had a significant better PPT and executive function performance than the oldest group (75 and older), whereas no significant age differences were observed for handgrip strength. Multiple regression analysis adjusted for potential covariates, including MMSE scores, showed that TMT-A, TMT-B, and Digit symbol were significantly associated with PPT scores; however, no significant association was observed between executive function variables and handgrip strength. CONCLUSIONS: Hand dexterity is vulnerable to the effects of aging and, contrary to handgrip strength, it strongly associates with executive function, independent of global cognition. Our results suggest that assessing hand dexterity may help identify individuals at higher risk of impairment of executive function among high-functioning older adults.

Postoperative Bio-Chemoradiotherapy Using Cetuximab and Docetaxel in Patients With Cis-Platinum-Intolerant Core High-Risk Head and Neck Cancer: Protocol of a Phase 2 Nonrandomized Clinical Trial.

BACKGROUND: We confirmed the safety of postoperative bio-chemoradiotherapy using cetuximab and docetaxel in a small number of patients with cis-platinum-intolerant core high-risk head and neck cancer. OBJECTIVE: To assess treatment efficacy, we planned a phase 2 study of postoperative bio-chemoradiotherapy for patients with cis-platinum-intolerant core high-risk head and neck cancer and will compare the results to those of previously collected radiotherapy data. METHODS: Patients who underwent definitive surgery for oral cavity, laryngeal, oropharyngeal, or hypopharyngeal advanced cancer, whose postoperative pathological results indicated core high risk for recurrence (eg, positive margin in the primary site or extranodal extension) and who were cis-platinum-intolerant, will undergo postoperative bio-chemoradiotherapy. The primary end point is 2-year disease-free survival. RESULTS: The expected 2-year disease-free survival is set at 55%, and the calculated sample size is 35 patients, according to a statistical analysis based on previous reports. CONCLUSIONS: This treatment method is expected to improve the survival rate of patients with severe head and neck cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000031835; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000036355 (Archived by WebCite at http://www.webcitation.org/71fejVjMr).