Naomune Yamamoto

Cardio-Ankle Vascular Index as a Predictor of Cognitive Impairment in Community-Dwelling Elderly People: Four-Year Follow-Up

Background/Aim: The relation between markers of generalized atherosclerosis and cognitive impairment in old age is controversial. The aim of the study was to evaluate the cardio-ankle vascular index (CAVI) as a predictor of longitudinal changes in cognitive function in older individuals. Methods: We evaluated the cognitive function in elderly people with high (AS(+)) and low (AS(–)) values of CAVI each year over 4 years. Results: The changes in the Hasegawa Dementia Scale Revised (HDS-R) and the mini-mental state examination (MMSE) at 4 years were significantly larger in the AS(+) group (AS(+) vs. AS(–) = –1.8 ± 4.4 vs. 0.3 ± 2.8 points and –1.1 ± 3.0 vs. 0.1 ± 2.3 points, p = 0.008 and 0.03, respectively). The annual changes in the HDS-R were significantly decreased from baseline at 1 year later to 4 years later in AS(+) (baseline vs. 1, 2, 3, 4 years = 26.5 vs. 25.0, 25.5, 25.7, 24.8 points, p < 0.001); in comparison, the annual changes in MMSE significantly decreased from the baseline over the 4 years in AS (+) (baseline vs. 1, 2, 3, 4 years = 26.8 vs. 26.2, 25.8, 26.4, 25.7 points, p = 0.002). Conclusion: The results of this study suggest that elderly people with a high CAVI value are at a greater risk of cognitive decline.

Detrended Fluctuation Analysis Is Considered to Be Useful as a New Indicator for Short-Term Glucose Complexity

BACKGROUND This study clarified whether detrended fluctuation analysis (DFA) can evaluate how to advance the loss of complexity from impaired glucose tolerance (IGT) through mild diabetes mellitus (DM) to overt DM. METHODS Continuous glucose monitoring (CGM) was done during a 48-h interval for 59 subjects from multiple centers. Subjects were divided according to CGM data into those with impaired glucose tolerance (IGT) (n = 20), mild DM (n = 13), and overt DM (n = 26). The short-term (α1) and long-term (α2) range exponentials by DFA were compared among the three groups. RESULTS The value of α1 within 1h was significantly lower in the IGT group than in either of the other two groups (IGT vs. mild DM vs. overt DM, 1.53 ± 0.22 vs. 1.71 ± 0.17 vs. 1.77 ± 0.13, P<0.0001), and α1 within 2h differed significantly among the three groups (1.49 ± 0.13 vs. 1.57 ± 0.10 vs. 1.72 ± 0.10, P<0.0001). The α1 within 3h was significantly higher in overt DM than in either of the other two groups but did not change between IGT and mild DM (1.44 ± 0.12 vs. 1.52 ± 0.11 vs. 1.67 ± 0.09, P<0.0001). All short-term exponents decreased gradually but significantly as the window widened in all groups (P<0.0001). The α2 over 1h was significantly higher in overt DM but was unchanged in IGT and mild DM (1.22 ± 0.11 vs. 1.27 ± 0.12 vs. 1.36 ± 0.13, P = 0.0010). The α2 over 3h did not differ among the three groups. CONCLUSIONS Progressive loss of complexity in the glycemic profile occurred from the short-term range and spread to the long-term range concomitantly with the progression of the DM state.

Impact of outdoor temperature on prewaking morning surge and nocturnal decline in blood pressure in a Japanese population

Seasonal variations in blood pressure (BP) have often been attributed to meteorological factors, especially changes in outdoor temperature. We evaluated the direct association between meteorological factors and circadian BP variability. Twenty-four-hour ambulatory BP was monitored continuously for 7 days in 158 subjects. Mean awake, asleep, morning (first 2 h after waking) BP, prewaking morning BP surge (morning systolic BP (SBP)−mean SBP during the 2-h period before waking) and nocturnal BP decline were measured each day. We compared BP values for the lowest and highest days with regard to the daily mean outdoor temperature and mean atmospheric pressure. Morning BP and prewaking morning BP surge on the coldest day were significantly higher than those on the warmest day (morning SBP, 136.6±1.6 vs. 133.1±1.5 mm Hg, P=0.002; morning diastolic BP, 84.4±0.9 vs. 82.6±0.9 mm Hg, P=0.02; and prewaking morning BP surge, 20.8±1.3 vs. 15.3±1.3 mm Hg, P=0.0004). The magnitude of nocturnal BP decline on the coldest day was significantly greater than that on the warmest day (15.8±0.7 vs. 13.9±0.7%, P=0.01). Outdoor temperature is an important determinant of morning BP, prewaking morning BP surge and the magnitude of nocturnal BP decline. These findings may have important implications in management of hypertension and prevention of cardiovascular events.

Lifestyle intervention reversed cognitive function in aged people with diabetes mellitus: Two-year follow up

To clarify the reversibility of cognitive decline in elderly people with type 2 diabetes, we evaluated cognitive function in 55 elderly people with diabetes and 74 control subjects before and after lifestyle intervention. Lifestyle intervention has a beneficial effect on cognitive decline in elderly people with type 2 diabetes mellitus.

Insomnia Increases Insulin Resistance and Insulin Secretion in Elderly People

and D. Her CST score became normal (20/20). With hindsight, several hypotheses might explain the dramatic effects of valproate. First, valproate has high protein binding, more than 80%, mainly to albumin. Only free drug can cross the plasma membrane and bind with the receptor for pharmacological action. Free valproate concentrations mirror cerebral spinal fluid concentration. Valproate has a narrow therapeutic index, and toxicity may be encountered slightly above the upper end of the therapeutic range. For instance, a lowering of serum albumin from 40 to 30 g/L may double the amount of free valproate. In this patient, serum albumin was 24 g/L. Second, in renal failure, unknown compounds displace valproate from protein-binding sites and may increase the free fraction up to 20% to 30% (normally 10%). This patient had a toxic free fraction and concentration in the serum of 24% and 11 mg/L (normal range 5–10 mg/L) and liquor of 22% and 10 mg/L (normal range 5–10 mg/L). Third, mycophenolate is also a strongly protein-bound drug (92–98%) and may have further increased the free valproate level. Finally, this patient had an intermediatemetabolizer (CYP2C9 3) heterozygous genotype, which can also lead to a higher free valproate level. It was concluded that valproate intoxication caused by a too-high (toxic) free concentration could entirely explain the RPD. The subtherapeutic total serum valproate level was initially misleading. Neurotoxicity has been described only in patients with normal or high total levels of valproate. Conditions such as hypoalbuminemia and renal failure can lead to a significant increase in free concentrations, resulting in (neuro)toxicity even if the total valproate level is within or below therapeutic range. In patients with renal failure, hypoalbuminemia, or prescription of highly protein bound medication, monitoring of free valproate concentration is recommended. Free drug concentration of valproate is easily measured in clinical laboratories, and this method is widely available.

Cognitive function with subclinical hypothyroidism in elderly people without dementia: One year follow up

The effects of subclinical hypothyroidism (SCH) on cognitive function in older people are controversial. This unresolved issue presents a problem in clinical practice because SCH is prevalent among older patients, many of whom have already had some cognitive decline. Therefore, in this longitudinal study, we sought to clarify the effects on cognitive function of SCH without dementia in very old people.

Cerebrovascular Disease in Type 2 Diabetic Patients Without Hypertension

To the Editor: The close relationship between diabetes mellitus and arteriosclerosis of the cerebral arteries has recently been reported. However, in these studies, the subjects included older patients with hypertension, which itself is a significant risk factor for arteriosclerosis of the cerebral arteries.1–3 Thus, previous studies on the effect of diabetes on the development of sclerosis were confounded by hypertension and aging. Therefore, we examined relatively young patients with diabetes mellitus who did not have hypertension in order to clarify the influence of diabetes mellitus itself on the development of sclerosis of the cerebral arteries. The subjects included 30 patients with type 2 diabetes mellitus (DM). The subjects with DM did not have hypertension (systolic blood pressure <140 mm Hg, diastolic blood pressure <90 mm Hg) and had no history of cerebral infarction, diabetic retinopathy, diabetic neuropathy, or diabetic nephropathy. Among the 30 diabetic patients, 4 were being treated with insulin injections, 10 with oral hypoglycemic agents, and 16 with dietary therapy alone. The control group (C) consisted of 20 healthy adults without a history of diabetes, hypertension, or cerebral infarction. There were no significant differences in age (DM: 50.1±7.0 years versus C: 49.7±6.7 years), sex (DM: 21/9 versus C: 11/9 [M/F]), systolic blood pressure (DM: 120±11 mm Hg versus C: 117±10 mm Hg) between the …

Differences in heart rate variability in non-hypertensive diabetic patients correlate with the presence of underlying cerebrovascular disease

We previously showed that diabetes contributes to the development of sclerotic lesions in cerebral arteries. In this study, we attempted to clarify whether differences in heart rate variability in non‐hypertensive diabetic patients were dependent on the presence or absence of underlying cerebrovascular disease. Thirty diabetic subjects between 40 and 59 years of age and who had no prior history of hypertension were used in this study. Lacunar lesions (LA) were detected with magnetic resonance imaging and atherosclerotic lesions (AS) were detected using intra‐ and extracranial magnetic resonance angiography, and by ultrasonographic scanning of the carotid artery. Patients underwent a full clinical laboratory screening and a power spectrum analysis of their heart rate variability. Subjects were divided into two groups: those with and without LA. The low frequency/high frequency ratio (LF/HF ratio) was found to be significantly increased (P<0·01) in subjects with LA (2·2 ± 0·3) compared to those without LA (1·3 ± 0·1). When subjects were divided into groups based on their presence or absence of AS, high‐frequency power was found to be significantly reduced (P<0·05) in the subjects with AS (12·8 ± 3·4 ms) compared to those without AS (19·4 ± 1·7 ms). The LF/HF ratio was found to be significantly increased (P<0·05) in the subjects with AS (2·2 ± 0·3) compared to those without AS (1·4 ± 0·1). Our data suggested that atherosclerotic lesions in cerebrovascular diseased linked to decrease of vagal nerve activity in non‐hypertensive diabetic patients.

Intrinsic cardiovascular autonomic regulatory system of astronauts exposed long-term to microgravity in space: observational study

The fractal scaling of the long-term heart rate variability (HRV) reflects the ‘intrinsic’ autonomic regulatory system. Herein, we examine how microgravity on the ISS affected the power-law scaling β (beta) of astronauts during a long-duration (about 6 months) spaceflight. Ambulatory electrocardiographic (ECG) monitoring was performed on seven healthy astronauts (5 men, 52.0±4.2 years of age) five times: before launch, 24±5 (F01) and 73±5 (F02) days after launch, 15±5 days before return (F03), and after return to Earth. The power-law scaling β was calculated as the slope of the regression line of the power density of the MEM spectrum versus frequency plotted on a log10–log10 scale in the range of 0.0001–0.01 Hz (corresponding to periods of 2.8 h to 1.6 min). β was less negative in space (−0.949±0.061) than on Earth (−1.163±0.075; P<0.025). The difference was more pronounced during the awake than during the rest/sleep span. The circadian amplitude and acrophase (phase of maximum) of β did not differ in space as compared with Earth. An effect of microgravity was detected within 1 month (F01) in space and continued throughout the spaceflight. The intrinsic autonomic regulatory system that protects life under serious environmental conditions on Earth is altered in the microgravity environment, with no change over the 6-month spaceflight. It is thus important to find a way to improve conditions in space and/or in terms of human physiology, not to compromise the intrinsic autonomic regulatory system now that plans are being made to inhabit another planet in the near future.

Disaster-related psychiatric disorders among survivors of flooding in Ladakh, India

Background: Heavy rainfall in northern India in August 2010 caused flash floods, seriously damaging homes and infrastructure. There have been no major disasters in the history of Ladakh, and no surveys on post-disaster psychiatric disorders have been conducted in this area. Aims and methods: To examine the impact of this disaster in Ladakh one month post-disaster, we visited Choglamsar, located near the town of Leh, where the flood had the most severe impact. In total, 318 survivors (mean age: 58.6 years; female–male ratio: 59.7%; Tibetan refugees: 86.2%) participated in the survey. We used the two-item Patient Health Questionnaire (PHQ-2) along with questions covering background characteristics and disaster exposure. A psychiatrist interviewed the survivors with a single or double positive score in the PHQ-2 or with post-traumatic stress disorder (PTSD) symptoms. Results and conclusion: There were only two PTSD cases and five of major depressive disorders. PTSD and depression were less common in the Tibetan cultural areas than in other areas. The social background and temperamental characteristics of the Tibetan culture may play a suppressive role in psychiatric disorders.