The participants in this study were derived from the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA), which involves ongoing population-based biennial examinations of a cohort of approximately 2300 persons. The participants in the NILS-LSA were randomly selected from resident registrations and stratified by both decade of age and sex. The NILS-LSA is a comprehensive and interdisciplinary study to observe age-related changes and consists of various gerontological and geriatric measurements, including medical examinations, blood chemical analysis, body composition, anthropometry, nutritional analysis, psychological tests, physical function, and physical activity. Details of the NILS-LSA have been described elsewhere.
The baseline participants of this study were 1526 middle-age and elderly people (773 men and 753 women) who completed the second wave examinations of NILS-LSA between April 2000 and May 2002. Of these, 942 (61.6%, 481 men and 461 women) participated in the 8-yr follow-up surveys (NILS-LSA sixth wave examination from July 2008 to July 2010). The dropouts were 584 participants (292 men and 292 women). In male and female participants, the age at baseline of the dropouts was significantly higher than that of the participants who completed both examinations (t-test, P < 0.0001). In male participants, the ratios of stroke and ischemic heart disease histories in dropouts were significantly higher than those in participants who completed both examinations (chi-square test: stroke, P = 0.0002; ischemic heart disease, P = 0.0019). In female participants, there were no differences in the ratios of stroke and ischemic heart disease histories between the dropouts and the participants who completed both examinations. In male and female participants, the ratio of diabetes histories in dropouts was significantly higher than that in participants who completed both examinations (chi-square test: men, P = 0.0077; women, P = 0.0369). There were no differences in the ratios of hypertension and hyperlipidemia histories between the dropouts and the participants who completed both examinations in men or women. There were no differences in the ratios of severe atrophy in the frontal and temporal lobe between the dropouts and the participants who completed both examinations in men or women.
Participants with severe atrophy in the second wave examination were excluded because severe atrophy was of a high-end grade that cannot be used to determine further atrophy progression. Participants in their 40s were also excluded because few participants of this age show brain atrophy progression. Participants with a current medical history of Parkinson disease, dementia, or open head surgery were also excluded. Finally, the participants for this study were 381 men and 393 women.
The study protocol was approved by the Ethics Committee of the National Center for Geriatrics and Gerontology, and written informed consent was obtained from all participants.
Brain MRI Examination
Brain MRI was performed on participants at the second and sixth wave examinations using a 1.5-T scanner (Toshiba Visart, Tokyo, Japan) at the National Center for Geriatrics and Gerontology. Each participant's head was oriented in the scanner and stabilized during the scanning procedure by a head support. To establish slice orientation, the first scanning sequence consisted of a T1-weighted sagittal series (repetition time (TR) = 500 ms, echo time (TE) = 15 ms, 256 × 256 matrix) centered along the midline to define the orbitomeatal line. The second series of T1-weighted axial images (TR = 500 ms, TE = 15 ms, thickness = 8 mm, gap = 1.5 mm, 256 × 256 matrix) and T2-weighted axial images (TR = 4000 ms, TE = 120 ms, thickness = 8 mm, gap = 1.5 mm, 320 × 320 matrix) were oriented parallel to the orbitomeatal line. Fourteen slices were taken during each examination.
The presence and the degree of brain atrophy in the frontal and temporal lobes were assessed as no atrophy (I), mild atrophy (II), moderate atrophy (III), and severe atrophy (IV).[25,36] The participants were divided into two groups on the basis of results from the MRI in the second wave examination and sixth wave examination: the brain atrophy progression group (progress: degree of brain atrophy in the second wave < sixth wave) and the brain atrophy nonprogression group.
Daily Physical Activities and Total Energy Expenditure Assessments
We recorded the daily physical activities and total energy expenditures of the participants at the second wave examinations using a uniaxial accelerometry sensor (Lifecorder; Suzuken, Aichi, Japan). Lifecorder can assess two types of activity energy expenditure by activity level: energy expenditure of activities (with body movements) and energy expenditure of minor activities (working at a desk or reading a book). In this study, the activity energy expenditure was estimated as the energy expenditure of both types of activities. The total energy expenditure was determined as the sum of basal metabolism, energy expenditure of activities, energy expenditure of minor activities, and thermic effects of food. Participants wore the Lifecorder constantly (except while sleeping or bathing) for a 7-d period. We calculated the mean activity energy expenditure, the number of steps, and the total energy expenditure from 5 d of records (the maximum and the minimum records were excluded).
Body height and weight were measured using a digital scale. Body mass index (BMI) was calculated as weight divided by height squared (kg·m−2). Body fat mass was assessed by dual x-ray absorptiometry (QDR-4500A; Hologic, Bedford, MA). Lifestyle factors (including alcohol intake, smoking habit, and education levels), medical history, and use of medications were assessed with questionnaires. These questionnaires were confirmed by a physician at the medical examinations. All prescribed and nonprescribed medications used during the previous 2 wk were documented and brought by the participants; the physicians confirmed and coded them. Users of antihypertensive, antilipemic, or hypoglycemic medications were considered participants with hypertension, hyperlipidemia, and diabetes histories, respectively.
The results are shown as the mean ± SD or mean ± SE. Differences in continuous and class variables between the progression and the nonprogression groups were assessed with t-tests and chi-square tests, respectively. Cochran–Mantel–Haenszel statistics were used to examine the relationship between the age group and the brain atrophy progression. Multiple logistic regression models were fit to determine the associations of activity energy expenditure, number of steps, and total energy expenditure variables with frontal and temporal lobe atrophy progression while controlling for the baseline decade of age group, BMI, education history, medical history (stroke, ischemic heart disease, hypertension, hyperlipidemia, and diabetes),[4,12,24] and current smoking and alcohol intake as possible confounders.[9,37] Activity energy expenditure, number of steps, and total energy expenditure were modeled as sex-specific quintiles. Statistical testing was performed using the Statistical Analysis System release 9.1.3 (SAS Institute Inc., Cary, NC). Significant probability levels were considered to be less than 0.05.
Med Sci Sports Exerc. 2012;44(12):2362-2368. © 2012 American College of Sports Medicine