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exercise group than in the exercise with supplementation group.

DISCUSSION An exercise intervention without nutritional intervention may worsen nutritional status in frail older women. Nutritional requirements may increase in response to an exercise intervention, so it is recommended that frail older people avoid energy and protein deficiency, or increase protein intake, when they do strength training.2,7 The exercise group had lower iron intake and worse iron status after the intervention but still took in more iron than the control group. The enzyme supplement digests protein, carbohydrate, fat, and dietary fiber, improving absorption of amino acids, cholesterol, and sugars. Previous nutritional intervention studies used supplements,8 but some studies have suggested that the use of a supplement decreases nutritional intake from food. The major limitation of this study was that subjects were not allocated randomly to the groups. It was carefully checked that diet and physical activity were constant in the groups during the study. The exercise and exercise with supplementation groups had the same exercise program, although Barthel Index and grip strength were higher in the exercise group than in the exercise with supplementation group. Differences in these conditions or other factors may have affected the present results, although it appears that an exercise intervention without paying attention to nutrition may worsen nutritional status. Nutritional condition should be assessed when older people undertake an exercise intervention. Kazuko Ishikawa-Takata, PhD National Institute of Health and Nutrition, Tokyo, Japan Masahiro Nagaya, MD, PhD Geriatric Health Services Facility, Luminous Obu, Aichi, Japan Makoto Nakazawa, MD, PhD Aichi Rehabilitation Hospital, Aichi, Japan Toshiki Ohta, MD, PhD Nagoya Heart Center, Aichi, Japan

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REFERENCES 1. Daniels R, van Rossum E, de Witte L et al. Interventions to prevent disability in frail community-dwelling elderly: A systematic review. BMC Health Serv Res 2008;8:278. 2. Bauer J, Biolo G, Cederholm T et al. Evidence-based recommendations for optimal dietary protein intake in older people: A position paper from the PROT-AGE Study Group. J Am Med Dir Assoc 2013;14:542–559. 3. Shibata H, Kumagya O, Watanabe S et al. Improvement of nutritional status using digestive enzyme supplementation among frail elderly. Geriatr Med 1999;37:1355–1359. (in Japanese). 4. Yamada T, Jyou T, Sasaki M et al. The effect of digestive enzyme supplementation on NK activity among elderly. Digestive Organ Immunol 2005;42:137–140 (in Japanese). 5. Collin C, Wade DT, Davies S et al. The Barthel ADL Index: A reliability study. Int Disabil Stud 1988;10:61–63. 6. Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198. 7. Volkert D, Sieber CC. Protein requirements in the elderly. Int J Vitam Nutr Res 2011;81:109–119. 8. Milne AC, Potter J, Vivanti A et al. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Syst Rev 2009: CD003288.

CONTINUOUS POSITIVE AIRWAY PRESSURE THERAPY IMPROVES STAGE 1 AND STAGE 2 SLEEP NOCTURIA IN INDIVIDUALS WITH OBSTRUCTIVE SLEEP APNEA

To the Editor: Nocturia is a bothersome urological symptom, with an overall incidence that tends to increase with age, ranging from 2% at 20 to 59.3% at 80.1,2 Obstructive sleep apnea (OSA) is another common sleep disorder in elderly adults that reduces sleep quality by completely or partially obstructing the airway.3 Continuous positive airway pressure (CPAP) is effective in treating sleep-related breathing disorders.4 Sleep is a dynamic process, with cyclic changes in stages from non-rapid eye movement (REM) sleep to REM sleep. Data on nocturia and sleep architecture in elderly adults undergoing CPAP are scarce. The aims of the present study were to evaluate the efficacy of CPAP in elderly adults with nocturia and OSA and to determine the differences between various sleep stages.

METHODS ACKNOWLEDGMENTS The authors thank all participants and staff of the nursing homes for their positive participation in this study. This work was supported by a Comprehensive Research on Aging and Health, Health Labour Sciences Research Grant from the Ministry of Health Labour and Welfare. Conflict of Interest: There are no conflicts of interest. Author Contributions: Ishikawa-Takata, Nagaya, Nakazawa: study concept and design, statistical analyses, research data interpretation, discussion, critical manuscript review. Nagaya: selection of subjects and intervention program. Ohta: suggestions and advice. Ishikawa-Takata: drafting the article. All authors reviewed the final version of the manuscript and gave final approval of the version to be published. Sponsor’s Role: None.

Participant Enrollment The ethics review board China Medical University Hospital approved this prospective clinical study, which was conducted from February 2012 to January 2013. All participants were enrolled from a urology outpatient clinic, were aged 60 and older, and had a chief complaint of awakening to urinate twice or more nightly. Those who had habitual snoring and sleep apnea were referred to the sleep center. Individuals were excluded if they had a prostate larger than 30 g; residual urinary volume greater than 100 mL; a history of genital-urinary tract malignancy; active urinary tract infection; or a history of cerebrovascular accident, diabetes mellitus, heart failure, depression, or corticosteroid or diuretic use.

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The diagnosis of OSA was established according to standard full-night laboratory polysomnography (PSG). Individuals with an apnea-hypopnea index (AHI) of 5 or more per hour were diagnosed as having OSA.5 Eligible individuals with nocturia with OSA underwent titration of CPAP to determine an optimal pressure to address their apnea and hypopnea.

Data Collection Data were collected on age, sex, body mass index (BMI), clinical symptoms, and medications. Voiding diaries and PSG data, including sleep architecture, AHI, and arousal index, were recorded. Sleep specialists interpreted all PSG studies. The scoring of sleep and associated events were based on the 2007 American Academy of Sleep Medicine manual.5

Statistical Analysis Data were analyzed using SPSS for Windows, version 10.0 (SPSS, Inc., Chicago, IL). All continuous data were compared using a two-tailed Student t test. Categorical variables were compared using the chi-square or Fisher exact test. P < .05 was considered statistically significant.

RESULTS Clinical Features Of 25 men who underwent PSG screening, 23 met the OSA diagnostic criteria. Fourteen agreed to CPAP titration (mean age 74.2, mean BMI 23.8 kg/m2). The average AHI was 26.8 per hour.

Effect of CPAP on PSG Variables and Voiding Characteristics The mean CPAP titration pressure that eliminated the obstructive sleep breathing events was 6.1 cmH2O. CPAP treatment was associated with a reduction in mean AHI from 26.8 to 7.4 (P < .001) and mean arousal index from 37.9 to 26.9 per hour (P = .004). Total nocturia urine volume was reduced after CPAP titration (P = .02), but total sleep time did not change significantly. Nocturia frequency trended down but not statistically significantly (P = .06). The major effect of CPAP intervention was on Stage 1 (P = .001) and 2 (P = .04) sleep nocturia (Table 1).

Table 1. Nocturia Before and After Continuous Positive Airway Pressure (CPAP) Therapy Nocturia Events, n

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DISCUSSION To the best of the knowledge of the authors, this is the first pilot study of individuals with OSA and nocturia that shows the effect of CPAP on nocturia during different sleep stages. Twenty-three (92%) participants met the diagnostic criteria for OSA. The strong association between nocturia and OSA indicates that general practitioners should look for sleep disorders in elderly adults who present with nocturia. CPAP therapy significantly reduced nocturia events from 2.5 to 0.7 per night, especially in individuals with moderate to severe OSA.6 The data from the current study showed that nocturia in individuals with OSA occurred predominantly in Stage 1 sleep (47.8%) and that a CPAP intervention significantly reduced nocturia in Stage 1 and 2 sleep. Improvement in the arousal index and AHI was also observed. As a consequence, sleep quality would improve with a smoother respiratory pattern and a lower probability of arousal from environmental noises or a full bladder. This study had several limitations. First, it had a small sample size. Second, there is selection bias because only men were enrolled, and mean BMI was only 23.8 kg/m2. Third, adherence to CPAP was not good, and only 14 of 23 participants underwent CPAP titration. Eric Chieh-Lung Chou, MD Department of Urology, China Medical University Hospital, Taichung, Taiwan Department of Urology, China Medical University, Taichung, Taiwan Po-Fan Hsieh, MD Department of Urology, China Medical University Hospital, Taichung, Taiwan Kuo-Liang Chen, MD Chao-Hsiang Chang, MD Department of Urology, China Medical University Hospital, Taichung, Taiwan Department of Urology, China Medical University, Taichung, Taiwan Liang-Wen Hang, MD, PhD Department of Internal Medicine, Sleep Center, China Medical University Hospital, Taichung, Taiwan Department of Internal Medicine, China Medical University, Taichung, Taiwan Shinn-Jye Liang, MD Department of Internal Medicine, Sleep Center, China Medical University Hospital, Taichung, Taiwan

ACKNOWLEDGMENTS

Sleep Stage

Before CPAP

After CPAP

P-Value

1 2 Rapid eye movement Total events

11 5 7 23

4 2 4 10

.001 .04 .05

Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. This study was supported by a grant from China Medical University (DMR-100-067).

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Author Contributions: Chou: concept and design, drafting and revising article critically for important intellectual content, final approval of version to be published. Liang, Hsieh: design, drafting and revising article critically for important intellectual content, final approval of the version to be published. Chen, Chang: concept and design, revising article critically for important intellectual content. Hang: concept and design. Sponsor’s Role: None.

REFERENCES 1. Romero E, Krakow B, Haynes P et al. Nocturia and snoring: Predictive symptoms for obstructive sleep apnea. Sleep Breath 2010;14:337–343. 2. Yoshimura K. Correlates for nocturia: A review of epidemiological studies. Int J Urol 2012;19:317–329. 3. Bixler EO, Vgontzas AN, Ten Have T et al. Effects of age on sleep apnea in men: I. Prevalence and severity. Am J Respir Crit Care Med 1998;157:144–148. 4. Sullivan CE, Issa FG, Berthon-Jones M et al. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 1981;1:862–865. 5. Iber C, Ancoli-Israel S, Chesson A et al. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Darien, IL: American Academy of Sleep Medicine, 2007. 6. Margel D, Shochat T, Getzler O et al. Continuous positive airway pressure reduces nocturia in patients with obstructive sleep apnea. Urology 2006;67:974– 977.

REGULAR ASPIRIN USE DOES NOT REDUCE RISK OF COGNITIVE DECLINE To the Editor: Regular aspirin use is routinely recommended for protection against cerebrovascular and cardiovascular events. Although cerebrovascular pathology contributes to risk of dementia, it is not well established whether aspirin use attenuates this risk. Previous work has demonstrated that transient ischemic attack (TIA) or report of stroke-like symptoms is associated with risk of cognitive impairment in cross-sectional analyses1 and with incident cognitive decline during longitudinal follow-up2 in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) study.3 The objective of the current study was to determine whether regular aspirin use protects against incident cognitive decline according to REGARDS. REGARDS has enrolled 30,239 participants for whom extensive demographic and health data have been collected. Several cognitive assessments have occurred during longitudinal follow-up of the cohort. A measure of global cognitive status, the Six-Item Screener (SIS), has been administered annually since 2003. Additional cognitive measures were subsequently added to the protocol for consistency with the 5-minute neuropsychological battery that the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Standards recommend.4 These tests, administered every 2 years, evaluate memory (Word List Learning (WLL) and Word List Recall (WLR)) and executive function (Animal Fluency Test (AFT) and Letter Fluency (LF)). Longitudinal SIS data were available for 23,915 participants who were cognitively normal at baseline (SIS > 4): 38% black, 43% female, mean age 64  9.2 at

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enrollment, average follow-up 5.9 years. Analyses of the SIS data indicate that those who did not use aspirin regularly had a higher likelihood of incident impairment according to the SIS (SIS < 5 on most-recent assessment) in univariate models (odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.09–1.13), but after adjustment for demographic factors, the association between regular aspirin use and incident impairment on the SIS was no longer significant (OR = 0.99, 95% CI = 0.89–1.09). Additional inclusion of Framingham Stroke Risk total scores or individual factors did not change this finding. For separate analyses of cognitive change on the WLL, WLR, AFT, and LF measures, difference scores were calculated based on each participant’s first and last assessments on each measure, adjusted for initial score values. There were 12,231 participants with longitudinal WLL data: 35% black, 56% female, mean age 64  8.4, average follow-up 3.6 years. In analysis of covariance models, the association between aspirin use and change in WLL score was significant before (Model 1) but not after adjustment for demographic characteristics (Model 2) or risk factors (Models 3 and 4). Analysis of the WLR data produced similar findings. The effect of adding each demographic variable individually was studied to understand the difference in association between aspirin use and change in WLL and WLR scores due to demographic factors, and it was found that age was the dominant factor responsible for the effect attenuation. Similar results were obtained for AFT and LF (Table 1). The protective effects of aspirin against heart disease and as a secondary preventive treatment for stroke are well

Table 1. Multivariable Results for Cognitive Change Scores According to Aspirin Use Cognitive Test

Model 1

Word List Learning (n = 12,231) Aspirin users 0.099 Nonaspirin users 0.418 P-value

Continuous positive airway pressure therapy improves stage 1 and stage 2 sleep nocturia in individuals with obstructive sleep apnea.

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