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Longitudinal changes in body mass index and body composition over 3 years and relationship to health outcomes in Hong Kong Chinese age 70 and older.

OBJECTIVES: To determine longitudinal changes in body mass index (BMI) and body composition with age and the relationship between these changes with mortality, morbidity, functional capacity, and other health outcome measures. DESIGN: A 3-year longitudinal study of a random sample of community-living subjects. SETTING: Older Chinese in the Hong Kong Special Administrative Region of China. PARTICIPANTS: Two thousand and thirty-two Chinese subjects age 70 and older recruited territory-wide by proportional random sampling. MEASUREMENTS: Baseline information collected included medical history, self-perceived health, Barthel Index, Geriatric Depression Score, time taken to complete a 16-foot walk, height, weight, mid-arm circumference, arm skin-fold thickness, and waist/hip ratio. Body composition was calculated from prediction equation. Outcome measures included mortality, development of new diseases, Barthel Index, time taken for 16-foot walk, self-perceived health, and Geriatric Depression Score. RESULTS: All parameters, with the exception of triceps skin-fold thickness in men, decreased, regardless of presence or absence of disease. The decrease in arm circumference, triceps skin-fold thickness, and total body fat (TBF) was greater in women than in men, whereas men had a greater decrease in fat-free mass (FFM). Even in the absence of disease, three times as many subjects lost > or =5kg in weight as gained > or =5kg (15% vs. 5%), and only age could be identified as a contributing factor to this weight loss. In the absence of disease, lower anthropometric indices were associated with greater mortality, development of new disease (in women only), dependency, and poor performance measure. Waist-hip ratio was not associated with mortality or any other health outcomes. Decrease in both FFM and TBF were associated with worse outcomes, the effect being more marked in women. CONCLUSION: In the older population, changes in weight and body composition occur even in the absence of disease and are associated with mortality and physical functioning level. Weight loss rather than weight gain appears to be more important in this population, and promotion of life-style interventions targeted at weight maintenance would be important.

Activities of Daily Living↗

Longitudinal change in language production: effects of aging and dementia on grammatical complexity and propositional content.

Mixed modeling was used to examine longitudinal changes in linguistic ability in healthy older adults and older adults with dementia. Language samples, vocabulary scores, and digit span scores were collected annually from healthy older adults and semiannually from older adults with dementia. The language samples were scored for grammatical complexity and propositional content. For the healthy group, age-related declines in grammatical complexity and propositional content were observed. The declines were most rapid in the mid 70s. For the group with dementia, grammatical complexity and propositional content also declined over time, regardless of age. Rates of decline were uniform across individuals. These analyses reveal how both grammatical complexity and propositional content are related to late-life changes in cognition in healthy older adults aswell as those with dementia. Alzheimer's disease accelerates this decline, regardless of age.

Aged↗

Longitudinal changes of metacarpal cortical striation in Graves' disease.

RATIONALE AND OBJECTIVES: The authors verify whether metacarpal cortical striation can be used to assess longitudinal changes in bone turnover in Graves' disease. METHODS: Eight patients with untreated Graves' disease (5 men, 3 women; age 36 +/- 12 years) and six patients with the disease in remission (1 man, 5 women; age 38 +/- 12) were studied. Posteroanterior radiographs of the bilateral hands were obtained using fine-grain mammography film and direct magnification. Three observers independently determined the grade of cortical striation (striation index; SI) of the second and third metacarpals in randomly presented radiographs. RESULTS: The SI determined by all observers decreased significantly after the beginning of antihyperthyroid therapy compared with the SI before treatment (P < 0.05). Significant correlation was found between the observers' assessments (r = 0.74, P < 0.001). The average kappa value and percent agreement were 0.27 and 51.8%, respectively. Intraobserver variability provided relatively good kappa statistics (kappa: 0.56; percent agreement: 79.9%). Longitudinal decrease in the SI was in accordance with a decline in urinary pyridinoline cross-link excretion, a decline in serum osteocalcin, and an increase in bone mineral density of lumbar spine. CONCLUSIONS: The change in the SI can be used to detect increased and decreased bone turnover. Thus, the SI can be used as one index of bone turnover in patients with Graves' disease.

Absorptiometry, Photon↗

Longitudinal changes of circadian leptin, insulin and cortisol plasma levels and their correlation during refeeding in patients with anorexia nervosa.

OBJECTIVE: To study the longitudinal changes in plasma levels of leptin, insulin and cortisol during the transition from the state of starvation to the state of refeeding focussing on diurnal secretion characteristics and their temporal relationships. DESIGN: Leptin, insulin and cortisol were measured every 2h for 24h during acute starvation (T1). Sampling was repeated after reaching half the target-body mass index (BMI) (T2) and again at target-BMI (17. 5kg/m(2); T3). The temporal relationships between the diurnal secretion patterns were assessed by cross-correlation analysis. RESULTS: Although BMIs at T1 were uniformly low, leptin levels varied widely within a range clearly below normal levels (0.03-1. 7microg/l). With increasing body fat during the course of refeeding, mean leptin levels increased from 0.64microg/l (range: 0.27-1. 73microg/l) (T1) to 1.61microg/l (range: 0.36-4.2microg/l) (T2) and to 3.67microg/l (range: 0.7-9.8microg/l) (T3). Circadian leptin secretion patterns showed maximal values uniformly around 0200h and minimal values around 0800h at all stages of the study. At all three weight levels, plasma leptin levels were highest between midnight and the early morning hours and lowest around the late morning hours. Refeeding neither profoundly changed secretion patterns of leptin nor did it change the positive, time-delayed relationship between leptin and insulin with increments in insulin secretion preceding those of leptin by 6h. A temporal relationship between leptin and cortisol could not be demonstrated in the state of semistarvation but emerged after a substantial weight gain; at that time, leptin increases preceded cortisol increases by 8h. CONCLUSIONS: Absolute leptin, insulin and cortisol levels are profoundly changed during starvation in anorectic patients, while refeeding, paralleled by a BMI gain, reverses these changes. During refeeding the relationship between leptin and cortisol changed profoundly, showing no significant correlation in the state of starvation, whereas at T3 after refeeding a strong inverse relationship could be observed. Leptin and insulin did not correlate significantly at any of the three stages studied.

Adult↗

Longitudinal changes in intake and food sources of calcium from childhood to young adulthood: the bogalusa heart study.

OBJECTIVE: To examine changes in calcium intake and food sources of calcium from childhood to young adulthood in a longitudinal sample. METHODS: Information on food and nutrient intake was derived from a single 24-hour dietary recall collected on children who participated in a cross-sectional survey at age 10 and again in young adulthood. A cohort of 237 young adults who participated in the 1989-1991 young adult survey (ages 19 to 28 years) also participated in one of three cross-sectional surveys from 1973 to 1978 at 10 years of age. Repeated measures analysis of variance was applied to examine the longitudinal changes in intake of calcium and food sources from childhood to young adulthood. RESULTS: Total calcium intake at age 10 was not significantly different than total calcium intake of those same individuals when they were young adults. Gender and ethnic differences were observed within the two age groups. In both childhood (age 10 years) and young adulthood, African-American females had significantly lower total calcium intake than Euro-American males. However, this ethnic difference in total calcium intake did not exist after adjusting for energy intake. Calcium intake per 1000 kcal was significantly lower in females than males at age 10, but not in young adulthood. A large percentage of 10-year-olds did not meet the RDA or AI for calcium intake (54% and 88%, respectively), and this was also shown when they were young adults (77% and 75%, respectively). CONCLUSIONS: More effective nutrition educational efforts are needed to emphasize the importance of adequate calcium intake and the major food sources of calcium, beginning early in childhood and continuing into young adulthood.

Adolescent↗

Longitudinal changes in serum cholesterol in man: an epidemiologic search for an etiology.

Serum cholesterol levels were determined in 1011 male participants of the Baltimore Longitudinal Study of Aging. This study presents the longitudinal changes in serum cholesterol from 1 July 1963 to 30 June 1977. Serum cholesterol values dropped 6% between 1970 and 1972. The span of this study was divided into two eras, one preceding and one following the drop. The effects of obesity, selected dietary constituents and physical activity were examined in an attempt to explain the secular change in serum cholesterol. Serum cholesterol levels were not significantly correlated to levels of weight or body mass index. Changes in weight were significantly positively correlated with changes in serum cholesterol. Overall, however, the study population did not experience a significant drop in weight and therefore, this relationship could not explain the observed drop in serum cholesterol. There were virtually no significant correlations between the absolute value of any of the dietary variables examined and the absolute level of serum cholesterol. There were significant but small changes in most dietary constituents; however, only changes in caloric intake were significantly positively correlated with changes in serum cholesterol. Because the overall change in caloric intake was small, it could explain less than 1 mg/dl of the 11 mg/dl drop. There was no overall change in physical activity. No significant correlations were found between either the level or change in physical activity and the level or change in serum cholesterol. It is concluded that neither weight nor physical activity could account for the observed changes in serum cholesterol. Changes in dietary constituents were significant and in a direction which would predict a lower serum cholesterol. However, for the group, dietary changes could not fully explain the drop in serum cholesterol. For individuals, the changes in diet poorly predicted changes in serum cholesterol. It is suggested that the observed secular drop in serum cholesterol may be due to factor(s) other than those studied.

Adolescent↗

Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus.

OBJECTIVE: This study prospectively evaluated the longitudinal changes in insulin sensitivity, insulin response, and endogenous (primarily hepatic) glucose production and suppression during insulin infusion in women with normal glucose tolerance (control) and gestational diabetes mellitus before and during a planned pregnancy. STUDY DESIGN: Eight control subjects and 7 subjects in whom gestational diabetes mellitus developed were evaluated with an oral glucose tolerance test, an intravenous glucose tolerance test, and hyperinsulinemic-euglycemic clamp with infusion of [6,6 (2)H2 ]glucose before conception and at 12 to 14 and 34 to 36 weeks' gestation. Insulin response was estimated as the area under the curve during the intravenous glucose tolerance test. Basal endogenous glucose production was estimated from isotope tracer dilution during steady state with [6,6 (2)H2 ]glucose and suppression during insulin infusion. Insulin sensitivity to glucose was defined as the glucose infusion rate required to maintain euglycemia during steady-state insulin infusion. Body composition was estimated with hydrodensitometry. Data were analyzed with 2-way analysis of variance with repeated measures for 2 groups. RESULTS: There were increases in first-phase (P =.006) and second-phase (P =. 0001) insulin responses in both groups with advancing gestation, but the increase in second-phase response was significantly greater (P =. 02) in the gestational diabetes mellitus group than in the control group. Basal glucose production increased significantly (P =.0001) with advancing gestation, and there was resistance to suppression during insulin infusion in both groups (P =.0001). There was less suppression of endogenous glucose production however, in the gestational diabetes mellitus group than in the control group (P =. 01). Insulin sensitivity decreased with advancing gestation in both groups (P =.0001), and there was lower insulin sensitivity in the gestational diabetes mellitus group than in the control group (P =. 04). Significant decreases in insulin sensitivity with time (P =. 0001) and between groups (P =.03) remained when the data were adjusted for differences in insulin concentration or residual hepatic glucose production. CONCLUSION: Obese women in whom gestational diabetes mellitus develops have a significant increase in insulin response but decreases in insulin sensitivity and suppression of hepatic glucose production during insulin infusion with advancing gestation with respect to a matched control group. These metabolic abnormalities in glucose metabolism are the hallmarks of type 2 diabetes, for which these women are at increased risk in later life.

Adult↗

Longitudinal changes in brain CT scans and development of dementia in Down's syndrome.

To determine the relationship of the development of dementia to longitudinal changes in brain CT scans in patients with Down's syndrome (DS), we studied 14 Japanese DS patients at an interval of 10 years. The age at entry to the study was 35.7 +/- 9.9 (mean +/- SD) years in 1989 when we did the first CT scans. We performed the second CT scans in 1999 and quantitatively compared them with those taken in 1989. The 4 oldest of the patients (the demented group, 55.3 +/- 1.4 years of age in 1999) developed symptoms of cognitive decline before 1999. The younger 10 (the non-demented group, 41.9 +/- 9.0 years of age in 1999) remained stable in cognitive function until 1999. Despite the clear difference between the demented and the non-demented group in brain atrophy in 1999, CT measures of the demented group were similar to those of the non-demented group in 1989. These results indicate that age is a better predictor of dementia than imaging studies and that CT does not show a quantitative difference between the demented and the non-demented group before the onset of dementia.

Adult↗

Longitudinal changes in higher-level functional capacity of an older population living in a Japanese urban community.

This study examined the present state and longitudinal changes in higher-level functional capacity in a Japanese urban community. Persons aged 65-84 years living in a suburb of central Tokyo participated in a baseline survey held in 1991 (n = 814) and followed-up for 8 years. Outcome measures were disabilities in: instrumental self-maintenance (IADL), the intellectual activity scale (intellectual activity) and the social role scale (social role), as measured by subscales of the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-index of competence). At baseline among the three subscales, both older men and women had the highest prevalence of disability in social role, followed in turn by intellectual activity and IADL disability. The 8-year longitudinal survey on subjects who had no initial disability (229 men and 235 women) in all three subscales of TMIG-index of competence demonstrated that they were most likely to lose social role function with advancing age, followed in turn by intellectual activity and IADL. The Cox proportional hazard model analysis for all 814 participants revealed that baseline level of social role and intellectual activity significantly predicted the new onset of IADL disability during the 8-year follow-up period even after controlling for gender, age, and chronic medical conditions. In summary, disability in social role and intellectual activity do not only likely precede IADL disability, but also predict significantly the future onset of IADL disability in a Japanese urban community older population.

Activities of Daily Living↗

Longitudinal changes in serum lipids of elderly Europeans. SENECA Investigators.

OBJECTIVE: To describe the serum total cholesterol, lipoprotein cholesterol and triglyceride concentrations in elderly people from the SENECA follow-up study and report on longitudinal changes in these lipid concentrations over a four-year follow-up period. DESIGN: Longitudinal study including baseline measurements taken in 1988/1989 which were repeated in 1993. SUBJECTS: In 1993 lipid concentrations were assayed in blood serum collected from 1181 elderly men and women, born from 1913 to 1918 and living in twelve small towns in ten European countries and one town in the USA. 1062 of these subjects had also participated in the baseline study. RESULTS: Mean concentrations ranged from 4.91 to 6.72 mmol/l for total cholesterol, 1.15 to 1.64 mmol/l for HDL cholesterol, 3.04 to 4.47 mmol/l for LDL cholesterol and 1.03 to 1.79 mmol/l for triglycerides. Thirty-two per cent of European men and 18% of women had plasma total cholesterol concentrations below 5.16 mmol/l; 32% of men and 56% of women had HDL cholesterol concentrations exceeding 1.42 mmol/l. Total- and HDL-cholesterol concentrations, and the HDL:total cholesterol ratio were higher in women than in men. Despite large variations between towns no clear north-south gradient was observed. Yet, lowest values for LDL cholesterol tended to be located in the south, while the highest values for LDL cholesterol showed up in the north. Comparisons between the 1989 and 1993 surveys revealed a significant decrease in total cholesterol and an increase in the HDL:total cholesterol ratio without significant variation in HDL cholesterol or triglyceride concentrations. CONCLUSION: Though serum lipid concentrations varied widely across Europe, a marked decline in total cholesterol values along with an increase in the HDL:total cholesterol ratio occurred across the SENECA towns.

Aged↗

Longitudinal changes of peritoneal function calculated by personal dialysis capacity in a patient after long-term continuous ambulatory peritoneal dialysis.

In the present study, we investigated longitudinal changes in peritoneal function, as calculated by the personal dialysis capacity (PDC) test, after patient withdrawal from 17 years of continuous ambulatory peritoneal dialysis (CAPD). In July 1982, a 42-year-old female was started on CAPD because of chronic renal failure. She performed CAPD without any trouble for 17 years. In July 1999, hemodialysis was introduced because of ultrafiltration failure. The CAPD catheter remained in place, and the patient subsequently performed intra-abdominal lavage, using a standard peritoneal dialysis (PD) solution, for 3 years. A PDC test was performed every 6 months before and after withdrawal from CAPD. In July 1999, the PDC test indicated a membrane area of 59,748 cm/1.73 m2, absorption of 2.72 mL/min/1.73 m2, plasma loss of 0.049 mL/min/1.73 m2, and ultrafiltration volume (UFV) of -666 mL/24 h. The dialysate-to-plasma ratio (D/P) of creatinine after 4 hours was 0.96. An abdominal computed tomography (CT) scan showed calcification of the peritoneum. In March 2000, the PDC showed an area of 44,929 cm/1.73 m2, absorption of 1.43 mL/min/1.73 m2, plasma loss of 0.092 mL/min/1.73 m2, and alpha UFV of 213 mL/24 h. In August 2000 (1 year after CAPD withdrawal), the area was 38,492 cm/1.73 m2; the absorption, 1.74 mL/min/1.73 m2; the plasma loss, 0.053 mL/min/1.73 m2; and the UFV, 348 mL/24 h. Long-term intra-abdominal lavage induced a gradual reduction in membrane area, which returned to the normal range (19,028 cm/1.73 m2) after 3 years. Ultrafiltration volume showed a gradual increase and reached its peak level (403 mL/24 h) in July 2002. After 3 years, the D/P creatinine was 0.82. However, an abdominal CT scan showed no change in the calcification of the peritoneum. From those data, we conclude that, in long-term CAPD patients, intra-abdominal lavage can induce improvement in peritoneal function, but not in calcification of the peritoneum.

Adolescent↗

Longitudinal changes in body composition and energy balance in lean women with normal and abnormal glucose tolerance during pregnancy.

OBJECTIVE: The objective of this study was to evaluate the longitudinal changes in energy expenditure and body composition in relationship to alterations in carbohydrate metabolism in women with normal and abnormal glucose metabolism. We hypothesized that women with decreased insulin sensitivity before conception would have less fat accretion and smaller increases in energy expenditure. STUDY DESIGN: Six women with normal glucose tolerance and 10 women with abnormal glucose tolerance were evaluated before conception, and in early (12 to 14 weeks) and late (34 to 36 weeks) gestation. Body composition was estimated by hydrodensitometry, resting energy expenditure, and glucose and fat metabolism by indirect calorimetry, endogenous glucose production by infusion of [6-6 2H2] glucose, and insulin sensitivity using a hyperinsulinemic-euglycemic clamp (40 mU/m2/min). RESULTS: There was a smaller increase in fat mass (1.3 kg [P = .04]) in early pregnancy in women with abnormal glucose tolerance before pregnancy. Indirect calorimetry measured gestational age-related increases in basal oxygen utilization, with or without correction for fat-free mass (VO2, P = .002), resting energy expenditure (expressed in kilocalories, P = .0001), and carbohydrate oxidation (P = .0003). The insulin-mediated elevation in VO2 increased in later gestation VO2 (P = .005), as did resting energy expenditure (P = .0001) and fat oxidation (P = 0.0001). However, there was a decrease in respiratory quotient (P = .0001), carbohydrate oxidation (P = .002), and nonoxidative carbohydrate metabolism (P = .0001) with advancing gestation during insulin infusion. In early pregnancy, changes in fat mass correlated inversely with changes in insulin sensitivity (r= -0.52, P = .04) and changes in basal VO2 correlated inversely with decreases in basal endogenous glucose production (r = -0.74, P = .01). CONCLUSION: In early gestation, the changes in maternal fat mass and basal oxygen consumption are inversely related to the changes in insulin sensitivity. This response in lean women with decreased insulin sensitivity before conception may have survival value by providing a larger amount of available substrate to meet fetoplacental needs during gestation.

Adult↗

Longitudinal changes in hearing aid satisfaction and usage in the elderly over a period of one or two years after hearing aid delivery.

OBJECTIVE: The objective of this study was to measure hearing aid satisfaction and usage for extended periods of time, up to 2 yr after hearing aid delivery, to determine whether longitudinal changes occur in the elderly for these outcome measures. DESIGN: A longitudinal study of hearing aid satisfaction and usage was performed in a group comprised of 134 elderly hearing aid wearers with these outcome measures obtained at 1, 6, and 12 mo postfit. A total of 49 of the original 134 elderly returned 2 yr after hearing aid delivery to complete the satisfaction and usage measures again. Multiple self-report measures of hearing aid satisfaction and hearing aid usage were obtained at each follow-up session. RESULTS: Most between-interval comparisons of the various measures of satisfaction and usage failed to reveal significant changes over time. However, some significant changes were observed in both satisfaction and usage. When such changes occurred, they were always in a direction that suggested a decrease in satisfaction or usage over time. Correlations across various postfit interval pairs were found to be positive, statistically significant, and moderate to strong in strength for all measures of satisfaction and usage. CONCLUSIONS: Although there were slight declines in hearing aid usage and satisfaction over time, measures of hearing aid satisfaction obtained at 1 mo postfit and of hearing aid usage obtained at 6 mo postfit are generally stable for up to 2 yr after hearing aid delivery.

Aged↗

Longitudinal changes in the refractive errors of children with tears in Descemet's membrane following forceps injuries.

BACKGROUND: Eyes with tears in Descemet's membrane secondary to forceps injuries frequently develop myopic astigmatism. Little is known regarding the longitudinal changes in the refractive errors of these eyes. METHODS: We performed a retrospective review of two children with tears in Descemet's membrane following forceps injuries to their left eyes. The refractive errors were followed longitudinally. RESULTS: Both patients developed myopic astigmatism in their affected eye and received optical correction and occlusion therapy. In both cases there was reduction in the myopic refractive error during early childhood. While the astigmatic refractive error was stable in one patient it decreased in the second patient. CONCLUSION: Myopia decreased in two children with myopic astigmatism secondary to tears in Descemet's membrane. Myopia in children with tears in Desemet's membrane is likely due to deformation of the cornea rather than form-deprivation.

Anisometropia↗

Longitudinal changes in airflow limitation and airway hyperresponsiveness in patients with stable asthma.

BACKGROUND: There are few long-term studies of the effects of treatment on the natural course of asthma. OBJECTIVE: To investigate the longitudinal changes in airflow limitation and airway hyperresponsiveness (AHR) in asthma. METHODS: We recruited 81 outpatients (never smokers) with stable asthma from the Kyoto University Hospital. They were evaluated for pulmonary function and AHR, expressed by forced expiratory volume in 1 second (FEV1) and the provocation dose that caused a 20% fall in FEV1 (PD20-FEV1), respectively, at entry and every 6 months over 3 years. We used random effects models to estimate the slopes of these changes, and then evaluated the relationship between these changes and their predictive factors. RESULTS: Using random effects models, the percentage of the predicted FEV1 (%FEV1) declined significantly but slightly at a mean rate of 0.5%/year (P = 0.002; 95% confidence interval, 0.3 to 0.8). The mean decline rate of FEV1 was 34 mL/year. However, Log(PD20-FEV1) showed significant improvement at a mean rate of 0.088 cumulative units/year (P < 0.001; 95% confidence interval, 0.053 to 0.122). Multiple regression analysis showed that the baseline values of %FEV1 and Log(PD20-FEV1) were the most significant predictive factors for their subsequent changes, respectively. CONCLUSIONS: In stable asthmatic patients treated according to international guidelines, airflow limitation progressed at a nearly normal rate over 3 years. However, AHR continued to improve despite its ceiling effects. Multiple regression analysis revealed a significant negative relationship between the initial values and the subsequent changes in airflow limitation and AHR, respectively.

Adult↗

Longitudinal changes in maternal serum 1,25-dihydroxyvitamin D and insulin like growth factor I levels in pregnant women who developed preeclampsia: comparison with normotensive pregnant women.

This study was undertaken to determine the longitudinal changes of serum 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) and insulin like growth factor I (IGF-I) levels at 20.7, 27.6, and 35.5 week periods of gestation in 40 pregnant women who remained normotensive (NT) and in 10 women who developed preeclampsia (PE). As compared with the first period, significant increases (P < 0.01) in maternal serum 1,25-(OH)(2)D and IGF-I were observed in the NT group. In the PE group, a similar increase in serum 1,25-(OH)(2)D was observed. In contrast, significant (P < 0.05) lower IGF-I levels were observed in the PE group at the moment of diagnosis. In addition a high incidence of subjects with low increase in IGF-I levels (<percentile 10) was found in the PE group (30% versus 5%, P = 0.02). In conclusion, circulating levels of 1,25-(OH)(2)D were not alterated in women before they developed PE. In the opposite, the high percentage of PE women with low increase in circulating IGF-I levels between the 20th and 35th week of pregnancy suggests early alterations of IGF-I synthesis in women developing PE.

Female↗

Longitudinal change in basal ganglia volume in patients with Huntington's disease.

Cross-sectional MRI studies demonstrating an association between caudate atrophy and symptom severity and duration of symptoms in patients with Huntington's disease (HD) have been assumed to reflect longitudinal changes in basal ganglia, but such neuropathologic progression has never been directly demonstrated. Subjects in the current study were 23 HD patients at various stages of the disorder who had two MRI images at least 10 months apart (mean interimage interval = 20.8 months). We measured volumes of caudate, putamen, and globus pallidus blind to the order of the images. For each structure, we calculated a change score by subtracting the volume obtained on the follow-up imaging from that obtained on the initial imaging. Results indicated significant decreases over time in caudate, putamen, and total basal ganglia volume. Age at onset and length of trinucleotide repeat correlated significantly with amount of volume change in caudate and total basal ganglia, even after controlling for length of interimage interval, duration of disease, and measures of symptom severity. Amount of change in basal ganglia structures was not significantly correlated with neurologic symptom severity at the time of the initial imaging or duration of symptoms. This is the first longitudinal MRI study to document progressive basal ganglia atrophy in HD, and suggests that quantitative neuroimaging with serial MRI may be useful in monitoring effectiveness of potential treatments. In addition, demonstration of greater rate of basal ganglia atrophy in patients with earlier symptom onset suggests that treatment effects may be more quickly observed in this subgroup of patients than in the general HD population.

Adult↗

Longitudinal changes of insulin-like growth factors and their binding proteins throughout normal pregnancy.

BACKGROUND: Insulin-like growth factors (IGFs) are anabolic proteins that are essential regulators of cell division, differentiation and growth. We describe the longitudinal changes in IGF-I, IGF-II and the binding proteins IGFBP-1, -2 and -3 before and during normal pregnancy. METHOD: Serum samples were taken before conception and then at 12, 24 and 36 weeks of gestation in 41 healthy women with uncomplicated pregnancies. We measured IGF-I using an automated chemiluminescent method, IGF-II and IGFBP-2 using in-house radioimmunoassays (RIAs), and IGFBP-1 and IGFBP-3 using commercial enzyme-linked immunosorbent assay (ELISA) and RIA kits, respectively. Because of the potential haemodilution effects during pregnancy, albumin was also measured in all samples. RESULTS: There was a significant fall in IGF-I during the first (36%) and second trimesters (21%) followed by an increase of 25% at 36 weeks. During pregnancy, the mean IGF-II concentrations fell by 12% at 12 weeks, 8% at 24 and 8% at 36 weeks compared with pre-conception values. When IGF-II results were adjusted for the haemodilution of pregnancy, its concentrations increased. During pregnancy, there was a rapid increase in mean IGFBP-1 levels by 17-fold (12 weeks), 24-fold (24 weeks) and 25-fold (36 weeks). IGFBP-2 concentrations fell after conception but started to increase towards term. This increase was more significant when adjusted for haemodilution. In contrast, IGFBP-3 concentrations increased significantly throughout pregnancy. CONCLUSION: Our data on the physiological changes of IGFs and their binding proteins add further evidence of the vital roles of these hormones throughout normal pregnancy.

Biomarkers↗