BACKGROUND:The apolipoprotein E ε4 (APOE ε4) allele, a major genetic risk factor for Alzheimer's disease, is associated with early atrophy in the precuneus and posterior cingulate cortex. Whether physical activity can mitigate this atrophy in high-risk APOE ε4 carriers remains unclear. This study aimed to determine whether physical activity can reduce such neurodegenerative changes in older adults carrying this allele. METHODS:This 10-year longitudinal study included 295 community-dwelling older adults (154 men and 141 women; age ≥65 years). Baseline physical activity was measured using accelerometers and analyzed according to activity intensity. Participants were categorized as APOE ε4 carriers or non-carriers. Volumes of the precuneus and posterior cingulate cortex were assessed using longitudinal magnetic resonance imaging. Sex-stratified linear mixed models examined the interaction between physical activity and APOE ε4 status on brain volume changes, adjusting for relevant covariates. RESULTS:The moderate-to-vigorous physical activity (MVPA) × APOE ε4 × year effect in women's left precuneus was significant unadjusted but not after false discovery rate (FDR; 16 models) and exploratory. Left precuneus volume declined significantly over 10 years regardless of MVPA level or APOE ε4 genotype (each p < 0.0001). However, among APOE ε4 carriers, greater time spent in MVPA slowed the rate of volume decline. No similar effect was observed in men. CONCLUSIONS:Higher habitual MVPA may be associated with slower left precuneus decline in APOE ε4-positive women. As this exploratory three‑way effect was FDR‑nonsignificant, targeted replication is needed to clarify the role of everyday activity in genetically vulnerable groups.

BACKGROUND:Personality traits have been associated with physical and mental health outcomes, yet their relationship with long-term care (LTC) needs remains understudied. OBJECTIVE:To examine the longitudinal effect of personality traits on the incidence of LTC needs among community-dwelling older adults in Japan. METHODS:Data were drawn from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA), involving 1003 older adults (≥65 years; mean age 73.0 ± 4.4; 48.6% male), who had no certification of LTC needs prior to baseline or within two years after baseline to prevent reverse causality. Personality traits were assessed at baseline using the Japanese version of the NEO Five-Factor Inventory. Participants were followed for up to 21.8 years (mean ± SD: 12.2 ± 5.7 years) to determine the incidences of long-term care (LTC) needs by the LTC Insurance System certificate. Cox proportional hazards models were used to estimate hazard ratios for the incidence of long-term care (LTC) needs per one standard deviation (1-SD) increase in each personality trait score, adjusting for relevant covariates. RESULTS:During follow-up, 583 individuals (58.1%) were newly certified for LTC needs. Higher levels of openness and conscientiousness were associated with reduced LTC needs incidence (HR [95% CI] 0.88 [0.81-0.95], p = 0.002; 0.91 [0.84-0.99], p = 0.030, respectively). No significant associations were found for neuroticism, extraversion, or agreeableness. CONCLUSION:Among older adults living in the community, higher openness and conscientiousness were protective against future LTC needs. These findings highlight the potential role of psychological traits in promoting autonomy and healthy aging.

Purpose: We constructed and validated a frailty-intrinsic capacity (FR-IC) index for predicting disability in community-dwelling older Japanese adults. Methods: This longitudinal cohort study included 1179 participants aged ≥60 years (mean age: 71.3 ± 7.4 years, 51 % men). A multidisciplinary geriatric team constructed a 35-item FR-IC index (score range: 0: robust to 1: severe frailty, accumulation model) comprising 15 domains incorporating the intrinsic capacity concept (IC-Vision, IC-Hearing, IC-Locomotor capacity, IC-Cognition, IC-Vitality, and IC-Psychological capacity) based on questionnaires widely used in Japan. To test predictive validity, age- and sex-adjusted Cox proportional hazard models estimated hazard ratios (HRs) for incident disability (care need levels ≥1) by FR-IC index quartiles using the cohort study’s existing data. Results: The mean FR-IC index score (32 items, three missing) was 0.08±0.05 (range: 0.00–0.31). During a mean follow-up of 9.0 ± 2.8 years, 284 (24 %) adults developed a disability. Compared with the lowest quartile, the adjusted HRs for developing an incident disability in the second to fourth quartiles were 2.32 (95 % confidence interval: 1.15–5.33), 3.18 (1.64–7.15), and 4.15 (2.14–9.32), respectively. The area under the curve of the FR-IC index for incident disability was 0.86. Among healthy participants, defined as robust by the baseline phenotypic physical frailty assessment (n = 437), sex- and age-adjusted HRs for incident support care through the second to third tertiles were 1.72 (0.79–4.30) and 2.51(1.17–6.22), respectively (trend P = 0.028). Conclusions: The novel FR-IC index can predict future disability among community-dwelling older Japanese adults. Integrating IC into frailty assessments provides a more comprehensive measure of aging.

BACKGROUND:The relationship between physical activity and hippocampal volume is important; however, most studies have used questionnaires to measure physical activity. We aimed to determine whether maintaining high levels of daily physical activity measured by an accelerometer reduces hippocampal atrophy in community-dwelling adults. METHODS:This cohort study used data from community-dwelling adults aged ≥60 years who participated in the National Institute for Longevity Sciences Longitudinal Study of Aging, which is a population-based prospective cohort study of approximately 2300 Japanese adults. Tertiles of step count, light-intensity physical activity, and moderate-to-vigorous-intensity physical activity (MVPA) were measured using accelerometers. Changes in the hippocampal and total gray matter volumes over approximately 10 years were obtained from high-resolution 3D T1-weighted magnetic resonance imaging (MRI) images. RESULTS:The analysis included 287 men and 264 women, with no history of head surgery, dementia, or stroke at baseline, who completed the MRI scans and follow-up surveys. Significant interactions between MVPA and years since baseline with whole and right hippocampal volumes were observed only in men (P < .05). Annual whole hippocampal atrophy volumes in the lowest, intermediate, and highest MVPA groups were -72.11, -58.25, and -59.53 mm3, respectively. Right hippocampal atrophy volumes were -36.93, -28.47, and -28.53 mm3, respectively. The total and right hippocampal volumes in the lowest MVPA group declined more rapidly than those in the other groups. CONCLUSIONS:Lower MVPA levels in men were associated with higher rates of both total and right hippocampal atrophy. The relationship between MVPA and atrophy may help develop dementia prevention strategies.

Purpose: To evaluate age-related changes in central corneal thickness (CCT) and investigate its relationship with other ocular parameters in community-dwelling Japanese adults through an 8-year longitudinal analysis. Design: A population-based, prospective longitudinal cohort study with baseline measurements from 1997 to 2000 and follow-up from 2006 to 2008. Subjects: A total of 631 community-dwelling Japanese adults aged 40 to 79 years (mean age: 55.7 ± 9.7 years) were enrolled from the National Institute for Longevity Sciences–Longitudinal Study of Aging. We excluded participants with corneal pathologies, contact lens use, glaucoma medication, or missing endothelial cell density measurements. Methods: Central corneal thickness was measured using calibrated specular microscopy (SP-2000; Topcon Corporation) at 2 time points approximately 8 years apart. Secondary measurements included corneal endothelial cell density, coefficient of variation in cell size, and corneal curvature. Mixed-effects models analyzed CCT changes, adjusting for sex, season, corneal endothelial cell density, and systemic health factors. Main Outcome Measures: Age-related changes in CCT, annual rate of CCT change across different age decades, and correlations between CCT changes and ocular/systemic parameters. Results: At baseline, adjusted CCT measurements were 520.2 ± 2.1 (standard error [SE]) μm, 514.1 ± 2.2 μm, 518.0 ± 2.5 μm, and 514.7 ± 3.7 μm for participants in their 40s, 50s, 60s, and 70s, respectively. Longitudinal analysis revealed a significant increase in CCT over time across all age groups (β = 0.7; SE = 0.1; P < 0.001). The annual CCT increase showed age-dependent slowing: 0.68 ± 0.08 μm for 40s, 0.62 ± 0.08 μm for 50s, 0.46 ± 0.09 μm for 60s, and 0.20 ± 0.14 μm for 70s with a statistically significant difference between 40s and 70s groups (β = −0.5; SE = 0.2' P = 0.003). Conclusions: This longitudinal analysis demonstrates that CCT increases over time in all age groups, with the rate of increase significantly slowing in older age groups. These findings contrast with previous cross-sectional studies suggesting CCT decreases with age, emphasizing the importance of longitudinal observations. These results have important implications for glaucoma diagnosis and refractive surgery safety evaluations in aging populations. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

BACKGROUND:Skin tactile perception may indicate frailty in older adults. Although gait performance is crucial for diagnosing frailty, its association with skin tactile perception has not yet been explored. OBJECTIVES:To examine the association between skin tactile perception and changes in step length, cadence, and gait speed in middle-aged and older adults. DESIGN:A longitudinal study (mean follow-up: 10.8 years) SETTING: Community-based survey PARTICIPANTS: A total of 1,403 middle-aged and older adults (aged 40-79 years, 53.6 % men) from the National Institute for Longevity Sciences-Longitudinal Study of Aging were included in this study. These participants completed the baseline survey (1997-2000) and at least two follow-up surveys (2000-2012), had no history of cerebrovascular disease, rheumatoid arthritis, or Parkinson's disease, and had complete data with no outliers in skin tactile perception measurements. MEASUREMENTS:Skin tactile perception was assessed using a two-point discrimination test. Step length (cm), cadence (steps/min), and gait speed (m/min) were evaluated on an 11-m walkway at a usual speed. RESULTS:The mean age of participants was 56.4 years. After full adjustment, mixed-effects models with splines revealed that the association between skin tactile perception and gait parameters varied with age. In adults aged 60 and above, we observed non-linear relationships between skin tactile perception and gait parameters. A consistent inflection point around 10 mm in tactile perception was identified across different age groups and gait parameters. CONCLUSIONS:Among community-dwelling middle-aged and older Japanese adults, skin tactile perception was associated with changes in gait parameters, particularly in those aged 60 and above. The 10-mm threshold in tactile perception may serve as a critical indicator for predicting changes in gait performance. Skin tactile perception tests may prove clinically useful for screening patients at elevated risk of impaired gait performance.

The risk factors on the transition from robustness to cognitive frailty (CF), characterized by concurrent cognitive impairment and physical frailty (PF), may vary through different transition routes. Data from the National Institute for Longevity Sciences-Longitudinal Study of Aging (2000−2012) were analyzed, including data for 1,061 older individuals (baseline age: 60–83 years; 51.5

This study examines the effect of personality on incident disabling dementia in community-dwelling older adults. We analyzed 898 adults (65 − 84 years) from the National Institute for Longevity Sciences-Longitudinal Study of Aging 2nd (2000 − 2002) or 5th (2006 − 2008) waves, with baseline established at their first personality questionnaire response. Participants with baseline cognitive impairment (MMSE ≤ 23), incident disabling dementia before baseline or within five follow-up years were excluded. Personality was assessed using NEO Five-Factor Inventory, measuring neuroticism, extraversion, openness, agreeableness, and conscientiousness. Disabling dementia was defined as ≥ rank II on the “Independence Degree in Daily Living for Older adults with Dementia” based on Doctor’s Opinion Paper (from baseline to January 2022). Cox proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for one standard deviation (SD) increase of personalities, controlling for age, sex, education, hearing and vision impairment, LDL cholesterol, depressive symptoms, physical activity, history of diabetes and hypertension, smoking, alcohol drinking, body mass index, social isolation, APOE ε4, and survey wave. A stratified analysis of APOE ε4 was also conducted. Over a mean (SD) follow-up of 12.3 (5.8) years, 196 individuals (21.8%) developed disabling dementia. Openness was negatively associated with overall incident disabling dementia risk (aHR [95%CI]: 0.82 [0.70–0.96]). Stratified analysis showed that openness reduced dementia risk in ε4 non-carriers (0.79 [0.67–0.94]), while conscientiousness reduced it in ε4 carriers (0.56 [0.37–0.84]). Openness may reduce incident disabling dementia risk, while conscientiousness might suppress disabling dementia onset in ε4 carriers.

Aim This study aimed to reestimate the prevalence of hearing loss based on the updated World Health Organization hearing loss classification and investigate whether existing hearing screening criteria could efficiently screen for frailty or cognitive deficit. Methods Data collected from community dwellers aged 40–91 years included 2325 samples. Health checkup hearing screening used were as follows: (A) 30 dB both at 1 and 4 kHz and (B) 30 dB at 1 kHz and 40 dB at 4 kHz were used. For participants aged ≥60 years, frailty according to the modified Cardiovascular Health Study criteria and cognitive deficit defined by a Mini‐Mental State Examination score <28 were assessed. Logistic regression was performed to obtain odds ratios for frailty and cognitive deficit. Results The rates of hearing loss using the updated World Health Organization classification in men were 8.6, 24.1, 54.2, 79.0 and 96.0% in their 40s, 50s, 60s, 70s and 80s and 3.7, 12.7, 36.4, 72.1 and 90.4% in women, respectively. Failing hearing screening using criterion A was associated with an increased risk of frailty, a sex‐adjusted odds ratio of 4.136 (95% confidence interval, 2.182–7.838) and an increased risk of cognitive deficit: 1.753 (95% confidence interval, 1.346–2.283). After adjusting for age and sex, the effects on frailty and cognitive deficit were no longer significant. The results were similar when criterion B was used. Conclusion Because of the high prevalence of hearing loss and the ability to utilize existing devices and methodologies, hearing screening for the elderly should be reviewed. Geriatr Gerontol Int 2025; ••: ••–•• .

Background: Although diets rich in carotenoids are associated with muscle health and a reduced risk of disability, the relationship between carotenoids and low lean body mass has not been fully elucidated. Objectives: This study aimed to clarify the relationship between serum carotenoid concentrations and low lean body mass over 4 y in older Japanese community-dwellers. Methods: A total of 750 adults aged >= 60 y participated in the National Institute for Longevity Sciences-Longitudinal Study of Aging. Individuals with a low lean body mass and muscle strength or gait speed at baseline were excluded. Baseline serum alpha-carotene, beta-carotene, beta-cryptoxanthin, zeaxanthin, lutein, and lycopene were measured. Low lean body mass was defined as appendicular lean mass relative to the measured height (ALM/ht(2)) of <7.0 kg/m(2) in males and <5.4 kg/m(2) in females, according to the criteria of the Asian Working Group for Sarcopenia 2019. A generalized estimating equation was used to estimate the odds ratio and 95% confidence interval for low lean body mass according to tertiles of total and individual carotenoids at baseline, adjusted for sex, age, season, follow-up months, education years, economic status, current smoking status, a history of ischemic heart disease, stroke, hypertension, dyslipidemia, diabetes mellitus, and metabolic equivalents. Results: Low serum total carotenoids were associated with low ALM/ht(2), and the odds ratios of low ALM/ht(2) in the third tertile of total carotenoids were significantly lower than those in the first tertile after adjusting for covariates. The odds ratios of low ALM/ht(2) in the third tertile of beta-cryptoxanthin were significantly associated with those in the first tertile after adjusting for covariates (P = 0.03); however, no trend was observed for this relationship. Conclusions: These findings indicate that low serum total carotenoids and serum beta-cryptoxanthin are associated with low lean body mass in older Japanese community-dwellers.

Abstract Objectives Cognitive and physical functions are both associated with disability and death. Recent studies have addressed the relationship between cognitive declines and physical declines; however, whether various facets of cognition are diversely associated with specific physical functions is yet to be ascertained. The present work examines the longitudinal associations between fluid and crystallized cognitive functions (Gf and Gc) and physical functions. Methods The sample consisted of 863 community-dwelling older adults (baseline age 60–79 years) from the National Institute for Longevity Sciences-Longitudinal Study of Aging. The participants were tested on a set of Gf and Gc tests and physical tests (grip strength and gait speed). We ran a series of Multivariate Latent Growth Curve models. Specifically, we tested the relationship between cognitive and physical functions in terms of baseline performance (intercept) and rate of change (slope). Results The slope–slope correlations between Gf and physical function were large (grip strength r = 0.64 and gait speed r = 0.68, ps < .001). By contrast, the slope correlations between Gc and physical functions were weak (rs ≤ 0.31) and barely or marginally significant (ps ≤ .06). Discussion The results show that distinct domains of cognitive functions have different associations with physical functions. Namely, the aging-associated declines in the tested physical functions are robustly correlated with the declines in Gf, but are only weakly correlated with the declines in Gc. Therefore, Gc measures may be poor proxies for the patient’s frailty and should be considered with caution in clinical assessment.

Purpose Evidence has suggested that adherence to a Japanese diet may be beneficial for health. However, its association with incident dementia remains unclear. The aim was to explore this association in older Japanese community-dwellers, taking apoprotein E genotype into consideration. Methods A 20-year follow-up cohort study involving 1504 dementia-free older Japanese community-dwellers (aged 65–82 years) living in Aichi Prefecture, Japan, was conducted. Based on a previous study, a 9-component-weighted Japanese Diet Index (wJDI9) score (range − 1 to 12) was calculated using 3-day dietary record data and used as an indicator of adherence to a Japanese diet. Incident dementia was confirmed by the Long-term Care Insurance System certificate, and dementia events occurring within the first 5 years of follow-up were excluded. A multivariate-adjusted Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia, and Laplace regression was used to estimate percentile differences (PDs) and 95% CIs (expressed in months) in age at incident dementia (i.e., dementia-free duration differences), according to tertiles (T1–T3) of wJDI9 scores. Results The median (IQR) follow-up duration was 11.4 (7.8–15.1) years. During the follow-up period, 225 (15.0%) cases of incident dementia were identified. Because the smallest prevalence of incident dementia was 10.7% for the T3 group of wJDI9 scores, to avoid inaccurately estimating the dementia-free duration of participants in the T3 group, the 11th PDs in age at incident dementia between the T1 and T3 groups of wJDI9 scores were estimated. A higher wJDI9 score was associated with a lower risk of incident dementia and a longer dementia-free duration difference. The multivariate-adjusted HR (95% CI) and 11th PDs (95% CI) in age at incident dementia for participants in the T1 vs. T3 group were 1.00 (reference) vs. 0.58 (0.40, 0.86), and 0 (reference) vs. 36.7 (9.9, 63.4) months, respectively. Each 1-point increase of the wJDI9 score was associated with a 5% lower risk of incident dementia ( P value = 0.033) and 3.9 (0.3, 7.6) additional months of dementia-free duration ( P value = 0.035). No differences were seen in sex or smoking status (current smoker vs. non-current smoker) at baseline. Conclusion These findings suggest that adherence to a Japanese diet defined by wJDI9 is associated with a lower risk of incident dementia in older Japanese community-dwellers, suggesting the benefit of the Japanese diet for dementia prevention.

Background and aims: Carriers of the apolipoprotein E 84 allele (APOE84) have an increased risk of developing dementia (e.g., Alzheimer's disease). However, it is less clear whether the APOE84 might also be involved in cognitive aging among the non-clinical population of older adults. While some studies have suggested that the APOE84 is related to accelerated cognitive decline in the normal aging process, others have failed to provide compelling evidence of such an impact. Notably, these discrepancies may depend on methodological short-comings, including short time spans, few assessments, and small sample sizes. The present study overcomes the above limitations and aims to clarify the impact of the APOE84 genotype on long-term longitudinal changes in cognitive functions in middle-aged and older adults in Japan.Methods and results: The data were retrieved from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) survey (N = 1832; 40 to 79 years of age at baseline). The participants were tested over nine waves covering a period of approximately 20 years. Latent Growth Curve (LGC) modeling was employed to test the impact of the interaction between APOE84 status and age on several cognitive functions. Four tests of the WAIS-R were administered: Information, Similarities, Picture completion, and Digit Symbol Sub-stitution Test (DSST). The results showed that the APOE84 carriers experienced a more pronounced decline in the DSST (p = 0.001) and Similarities (p = 0.022) tests. A similar tendency was found in the Information test (p = 0.034). By contrast, no effect was found in the Picture completion test (p = 0.563).Conclusions: APOE84 carriers seem to exhibit a steeper cognitive decline, which becomes apparent in old age. This effect is more robust in fluid cognitive skills (DSST) than crystallized cognitive skills (Information and Similarities). Overall, the APOE84 genotype may be a significant risk factor in normal (i.e., non-clinical) cognitive aging.

BackgroundWe conducted a study to investigate the relationship between optic nerve vertical cup-to-disc ratio (VCDR), body and ocular parameters, and brain lesions in middle-aged and above Japanese subjects, because although various risk factors for glaucoma have been previously characterised, it is theorised that there are unidentified neurological components.MethodsIn this population-based, age/gender-stratified, cross-sectional study that involved 2239 Japanese subjects (1127 men and 1112 women) aged 40 years and older (mean age: 59.3±11.7 years) living in the central geographical region of Japan who participated in the National Institute of Longevity Sciences–Longitudinal Study of Aging between 2002 and 2004, 4327 eyes and 2239 obtained MRIs of the head were evaluated. Multivariate mixed model and trend analyses were also performed.ResultsNo significant relationship between VCDR and brain lesions, other than basal ganglia lesions, was found. VCDR significantly increased with the high grade of basal ganglia infarct lesions (p=0.0193) and high intraocular pressure (p<0.0001) after adjustment for influential factors using a multivariate mixed model. A significant positive linear trend was observed between the predicted VCDR and the degrees of the basal ganglia lesions (p value trend=0.0096).ConclusionOur findings suggest that in subjects with higher grades of basal ganglia lesions, strict attention should be paid to elevated VCDR; however, further studies are needed to support/confirm our results.

BACKGROUND:Short-chain fatty acids (SCFAs) have been suggested to be associated with skeletal muscle mass maintenance. However, the role of dietary SCFAs in preserving muscle strength in the older population remains unclear. OBJECTIVES:To clarify the longitudinal association between the dietary intake of SCFAs and the development of low muscle strength in older community dwellers. METHODS:Data were obtained from the National Institute for Longevity Sciences-Longitudinal Study of Aging cohort. The participants included 441 men and 382 women who participated in the baseline survey (the fifth wave, between 2006 and 2008) and at least one follow-up examination (sixth to ninth waves, between 2008 and 2022) and were ≥60 years old and did not have low muscle strength (defined as a grip strength of <28 kg for men and <18 kg for women) at baseline. Baseline nutrient intakes were assessed with a 3-day dietary record. A generalized estimating equation was employed to estimate the odds ratio (OR) and 95 % confidence intervals (CIs) for low muscle strength per 1 standard deviation (SD) increase in the intake of SCFAs and other nutrients at baseline (adjusted for sex, age, follow-up time, baseline grip strength, physical activity, smoking, family income, education, and disease histories). RESULTS:The mean (SD) follow-up time and number were 7.8 (3.2) years and 3.2 (1.0) times, respectively. Approximately 8.1 % of the participants exhibited muscle strength loss in at least one follow-up assessment. The multivariate-adjusted OR (95 % CIs) was 0.77 (0.63-0.93) for each 1-SD increase in SCFA intake (268 mg/day), and the ORs for the highest through the lowest tertiles of SCFA intake were 1.00 (reference), 1.44 (0.95-2.17), and 1.83 (1.20-2.78), respectively (trend p = 0.005). The results remained significant after multivariate adjusting for energy or fat intake. CONCLUSION:Dietary intake of SCFAs may prevent muscle strength decline in community-dwelling older adults.

Objectives: This study aimed to determine whether food intake modifies the risk of developing hearing impairment (HI) in Japanese adults in their 40s.Methods: Data for individuals who were in their 40s with no HI at baseline and had participated in the survey multiple times were extracted from the National Institute for Longevity Sciences, Longitudinal Study of Aging. A total of 1846 samples observed for up to 11.5 years in 421 participants were included in the analyses. The average 3-day food intake was calculated. HI is defined as a pure-tone average of the better ear at frequencies of 0.5, 1, 2, and 4 kHz greater than 25 dB. The risk of developing HI in the 18 food groups was calculated longitudinally using multivariable cumulative data analyses.Results: Even after adjusting basic confounding factors, food groups, and baseline hearing level, significant associations were found between beverage consumption and risk increments for HI (odds ratio [OR] = 2.374, 95% confidence interval [CI]:1.141-4.940) and also between mushroom intake and risk reduction (OR = 0.215, 95% CI:0.069-0.667). Other foods did not consistently show significant results when the combination of analysis variables were changed.Conclusions: Although the effect of food on hearing is modest to the extent that the significance varies with the variables used in the analysis, the intake of beverages and mushrooms could potentially modify the risk of developing HI after middle age.(c) 2022 Japanese Society of Otorhinolaryngology-Head and Neck Surgery, Inc. Published by Elsevier B.V. All rights reserved.