The Longevity Project

Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial

TLP — Sat, 13 Oct 2012 17:51:23 +0000

OBJECTIVE:

To investigate the long term effect of hormone replacement therapy on cardiovascular outcomes in recently postmenopausal women.

DESIGN:

Open label, randomised controlled trial.

SETTING:

Denmark, 1990-93.

PARTICIPANTS:

1006 healthy women aged 45-58 who were recently postmenopausal or had perimenopausal symptoms in combination with recorded postmenopausal serum follicle stimulating hormone values. 502 women were randomly allocated to receive hormone replacement therapy and 504 to receive no treatment (control). Women who had undergone hysterectomy were included if they were aged 45-52 and had recorded values for postmenopausal serum follicle stimulating hormone.

INTERVENTIONS:

In the treatment group, women with an intact uterus were treated with triphasic estradiol and norethisterone acetate and women who had undergone hysterectomy received 2 mg estradiol a day. Intervention was stopped after about 11 years owing to adverse reports from other trials, but participants were followed for death, cardiovascular disease, and cancer for up to 16 years. Sensitivity analyses were carried out on women who took more than 80% of the prescribed treatment for five years.

MAIN OUTCOME MEASURE:

The primary endpoint was a composite of death, admission to hospital for heart failure, and myocardial infarction.

RESULTS:

At inclusion the women on average were aged 50 and had been postmenopausal for seven months. After 10 years of intervention, 16 women in the treatment group experienced the primary composite endpoint compared with 33 in the control group (hazard ratio 0.48, 95% confidence interval 0.26 to 0.87; P=0.015) and 15 died compared with 26 (0.57, 0.30 to 1.08; P=0.084). The reduction in cardiovascular events was not associated with an increase in any cancer (36 in treated group v 39 in control group, 0.92, 0.58 to 1.45; P=0.71) or in breast cancer (10 in treated group v 17 in control group, 0.58, 0.27 to 1.27; P=0.17). The hazard ratio for deep vein thrombosis (2 in treated group v 1 in control group) was 2.01 (0.18 to 22.16) and for stroke (11 in treated group v 14 in control group) was 0.77 (0.35 to 1.70). After 16 years the reduction in the primary composite outcome was still present and not associated with an increase in any cancer.

CONCLUSIONS:

After 10 years of randomised treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke.

Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, Køber L, Jensen JE.
Department of Endocrinology, Hvidovre Hospital, Kettegård alle 30, 2650 Hvidovre, Denmark.

High-fiber foods reduce periodontal disease progression in men aged 65 and older: the Veterans Affairs normative aging study/Dental Longitudinal Study

TLP — Wed, 27 Jun 2012 15:39:25 +0000

OBJECTIVES:

To determine whether foods that are good to excellent sources of fiber reduce periodontal disease progression in men.

DESIGN:

Prospective, observational study.

SETTING:

Greater Boston, Massachusetts, metropolitan area.

PARTICIPANTS:

Six hundred twenty-five community-dwelling men participating in the Department of Veterans Affairs Dental Longitudinal Study.

MEASUREMENTS:

Dental and physical examinations were conducted every 3 to 5 years. Diet was assessed using food frequency questionnaires (FFQs). Mean follow-up was 15 years (range: 2-24 years). Periodontal disease progression on each tooth was defined as alveolar bone loss (ABL) advancement of 40% or more, probing pocket depth (PPD) of 2 mm or more, or tooth loss. Good and excellent fiber sources provided 2.5 g or more of fiber per serving. Multivariate proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of periodontal disease progression and tooth loss in relation to fiber sources, stratified according to age younger than 65 versus 65 and older, and controlled for smoking, body mass index, calculus, baseline periodontal disease level, caries, education, exercise, carotene, thiamin and caffeine intake, and tooth brushing.

RESULTS:

In men aged 65 and older, each serving of good to excellent sources of total fiber was associated with lower risk of ABL progression (HR = 0.76, 95% CI = 0.60-0.95) and tooth loss (HR = 0.72, 95% CI = 0.53-0.97). Of the different food groups, only fruits that were good to excellent sources of fiber were associated with lower risk of progression of ABL (HR = 0.86 per serving, 95% CI = 0.78-0.95), PPD (HR = 0.95, 95% CI = 0.91-0.99), and tooth loss (HR = 0.88, 95% CI = 0.78-0.99). No significant associations were seen in men younger than 65.

CONCLUSION:

Benefits of higher intake of high-fiber foods, especially fruits, on slowing periodontal disease progression are most evident in men aged 65 and older.

Schwartz N, Kaye EK, Nunn ME, Spiro A 3rd, Garcia RI.
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA.
J Am Geriatr Soc. 2012 Apr;60(4):676-83. doi: 10.1111/j.1532-5415.2011.03866.x. Epub 2012 Feb 8.

Healthy Lifestyles Related to Subsequent Prevalence of Age-Related Macular Degeneration

TLP — Fri, 22 Jun 2012 08:08:33 +0000

Data on diet, physical activity, and smoking history were collected from 1325 participants in the Carotenoids in Age-Related Eye Disease Study (a subset of the Women’s Health Initiative Observation Study). This study includes the first estimates of associations among age-related macular degeneration (AMD), current US dietary guidelines, and physical activity.

The clinical implications of this study are substantial for both physicians and patients, because it provides evidence that a healthy lifestyle influences long-term preservation of vision. The findings indicate that patients should be counseled on the importance of following the US Dietary Guidelines along with maintaining a regimen of daily physical activity.

Smoking history is also an important modifiable risk factor for AMD, and this study found that women aged 50-69 years with fewer pack-years of smoking, healthier diets (as assessed by the modified Healthy Eating Index), and frequent physical activity had 3-fold lower odds of early AMD over a 6-year period. Of interest, frequency and not intensity of physical activity was more inversely related to prevalence of early AMD. Body weight, other than extreme obesity, was not significantly associated with prevalence of AMD.

Generalization of these data is limited because only women were included, the proportion of white patients was high, and participants generally were of high socioeconomic status. Genetic predisposition to AMD and its interplay with lifestyle could not be assessed.

AMD is associated with significant patient morbidity and financial burden, and its prevention is paramount. By following the US Dietary Guidelines, exercising daily, and avoiding smoking, patients can significantly reduce their risk for AMD.

Mares JA, Voland RP, Sondel SA, et al

Arch Ophthalmol. 2011;129:470-480

Pomegranate juice: a heart-healthy fruit juice ?

TLP — Mon, 30 Apr 2012 11:55:17 +0000

Pomegranate juice is a polyphenol-rich fruit juice with high antioxidant capacity. In limited studies in human and murine models, pomegranate juice has been shown to exert significant antiatherogenic, antioxidant, antihypertensive, and anti-inflammatory effects. Pomegranate juice significantly reduced atherosclerotic lesion areas in immune-deficient mice and intima media thickness in cardiac patients on medications. It also decreased lipid peroxidation in patients with type 2 diabetes, and systolic blood pressure and serum angiotensin converting enzyme activity in hypertensive patients. Thus, the potential cardioprotective benefits of pomegranate juice deserve further clinical investigation, and evidence to date suggests it may be prudent to include this fruit juice in a heart-healthy diet.

Basu A, Penugonda K.
Department of Nutritional Sciences, 301 Human Environmental Sciences, Oklahoma State University

Consumption of fried foods and risk of coronary heart disease

TLP — Wed, 01 Feb 2012 10:18:20 +0000

Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study

Objective
To assess the association between consumption of fried foods and risk of coronary heart disease.

Design
Prospective cohort study.

Setting
Spanish cohort of the European Prospective Investigation into Cancer and Nutrition.

Participants
40?757 adults aged 29-69 and free of coronary heart disease at baseline (1992-6), followed up until 2004.

Main outcome measures
Coronary heart disease events and vital status identified by record linkage with hospital discharge registers, population based registers of myocardial infarction, and mortality registers.

Results
During a median follow-up of 11 years, 606 coronary heart disease events and 1135 deaths from all causes occurred. Compared with being in the first (lowest) quarter of fried food consumption, the multivariate hazard ratio of coronary heart disease in the second quarter was 1.15 (95% confidence interval 0.91 to 1.45), in the third quarter was 1.07 (0.83 to 1.38), and in the fourth quarter was 1.08 (0.82 to 1.43; P for trend 0.74). The results did not vary between those who used olive oil for frying and those who used sunflower oil. Likewise, no association was observed between fried food consumption and all cause mortality: multivariate hazard ratio for the highest versus the lowest quarter of fried food consumption was 0.93 (95% confidence interval 0.77 to 1.14; P for trend 0.98).

Conclusion
In Spain, a Mediterranean country where olive or sunflower oil is used for frying, the consumption of fried foods was not associated with coronary heart disease or with all cause mortality.

Full article here (British Medical Journal)

The beneficial effects of regular exercise on cognition in REM sleep deprivation: Behavioral, electrophysiological and molecular evidence

TLP — Tue, 24 Jan 2012 09:40:21 +0000

Inadequate sleep is prevalent in modern societies and is known to profoundly impair cognitive function. We examined the impact of 4weeks of regular treadmill exercise on sleep deprivation induced spatial learning and memory, synaptic plasticity and related signaling molecules in area CA1 of the rat hippocampus. Rats were exercised on a treadmill and subsequently sleep-deprived for 24h using the modified multiple platform technique. Testing of learning and short-term memory performance in the radial arm water maze showed that although sedentary sleep deprived rats were severely impaired, exercised sleep deprived rats’ performance was normal. Extracellular recording from area CA1 of anesthetized rats revealed that early phase LTP (E-LTP) was markedly impaired in the sedentary sleep deprived animals, but was normal in the exercised sleep deprived group. Additionally, immunoblot analysis of CA1 area before (basal) and after expression of E-LTP indicated that the significant down-regulation of the brain derived neurotrophic factor (BDNF) and phosphorylated calcium-calmodulin dependent protein kinase II (P-CaMKII) levels in sleep deprived animals was prevented by the regular exercise regimen. The results suggest that the regular exercise protocol prevents the sleep deprivation induced impairments in short-term memory and E-LTP by preventing deleterious changes in the basal and post-stimulation levels of P-CaMKII and BDNF associated with sleep deprivation.

Zagaar M, Alhaider I, Dao A, Levine A, Alkarawi A, Alzubaidy M, Alkadhi K.

Neurobiol Dis. 2011 Dec 30.

Predictors of the Longevity Difference: A 25-Year Follow-Up

TLP — Fri, 20 Jan 2012 12:01:48 +0000

Twenty-two variables were found to be significant predictors of longevity among 252 panelists in a 25-year longitudinal study of aging. The strongest independent predictors for men were health self-rating, work satisfaction, and performance intelligence; for women they were health satisfaction, past enjoyment of intercourse, and physical function rating. These predictors could constitute a combined difference in longevity of 16 years for men and 23 years for women.

Erdman B. Palmore, PhD, Professor of Medical Sociology and Senior Fellow

Duke Center for the Study of Aging and Human Development, Box 3003, Duke Medical Center Durham, NC 27710

Alcohol Has a Dose-Related Effect on Parasympathetic Nerve Activity During Sleep

TLP — Fri, 30 Sep 2011 08:24:17 +0000

Background:? The aim of this study was to identify the acute effects of ethanol on the relationship between sleep and heart rate variability (HRV) during sleep. Methods:? Ten healthy male university students were enrolled in this study. An alcoholic beverage was given to each subject at a dosage of 0 (control), 0.5 (low dose: LD), or 1.0?g (high dose: HD) of pure ethanol/kg of body weight. All experiments were performed at 3-week intervals. On the day of the experiment, a Holter electrocardiogram was attached to the subject for a 24-hour period, and the subject was instructed to drink the above-described dosage of alcoholic beverage 100?minutes before going to bed; polysomnography was then performed for 8?hours. Power spectral analysis of the HRV was performed using the maximum entropy method, and the low- (LF: 0.04 to 0.15?Hz) and high-frequency (HF: 0.15 to 0.4 Hz) components along with LF/HF ratio were calculated. Results:? As alcohol consumption increased, the heart rate increased and the spectral power of HRV measured at each frequency range decreased. Higher doses of ethanol also increased the LF/HF ratio compared with the measured ratio of the control group. Conclusions:? Acute ethanol intake inhibits parasympathetic nerve activity and results in predominance of sympathetic nerve activity during sleep, in a dosage-dependent manner. The results of this study suggest that ethanol interferes with the restorative functions of sleep.

Sagawa Y, Kondo H, Matsubuchi N, Takemura T, Kanayama H, Kaneko Y, Kanbayashi T, Hishikawa Y, Shimizu T.

From the Department of Neuropsychiatry (YS, NM, TT, HK, YK, TK, TS), Akita University, School of Medicine, Akita, Japan; Saiseikai Nagasaki Hospital (HK), Nagasaki, Japan; and Akita Kaiseikai Hospital (YH), Akita, Japan.

Neuronal Shc: A gene of longevity in the brain ?

TLP — Fri, 16 Sep 2011 08:33:45 +0000

Aging is inevitable to all multi-cellular organisms, and each organism has its own lifespan. The species-specific lifespan seems determined genetically; however little is known about how the lifespan determined. During the last decades accumulative evidence indicates that there is certainly a set of genes that are involved in the lifespan determination. Among those dozens of genes, the Shc gene encoding a phosphotyrosine signal adaptor is of potential interests in mammalian aging and/or longevity determination. Shc is merely one form of a gene family, and accumulative evidence demonstrates the presence of additional Shc homologues that are strongly expressed in the nervous system. We hypothesize that lifespan is regulated primarily by the nervous system and/or brain, and neurally expressed Shc homologues play pivotal roles in relation to the evolution of longevity with quality of life. We discuss herein the recent progress of our understanding of the neuronally expressed Shc genes in comparision with p66-Shc as a candidate for the evolution of long life with higher quality of life in mammals.

Mori N, Mori M.

Department of Anatomy and Neurobiology, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

Cognitive reserve and its implications for rehabilitation and Alzheimer’s disease

TLP — Fri, 16 Sep 2011 07:46:57 +0000

According to the Cognitive reserve hypothesis, several factors related to mental engagement, such as level of education, type of occupation, leisure activities and social network, appear to affect the risk of developing clinical dementia. The present article provides an overview of the studies that have investigated the effects of mental engagement and cognitive stimulation specifically on dementia of the Alzheimer’s type (AD). Mental training and cognitive stimulation interventions in AD have been shown to be useful in increasing patients’ ability in performing activities of daily living (ADL), allowing them to maintain relative independence. Since cognitive engagement and stimulation are known to modify the brain processes to perform tasks, by recruiting alternative and more efficient networks, this review is especially focused on cognitive rehabilitation in AD patients, which has been shown to improve their global functioning and cognition. This perspective stresses the idea that cognitive reserve is not a fixed factor, but can be continuously modified by life experiences, even when the brain is already affected by neuropathology.

Liberati G, Raffone A, Olivetti Belardinelli M.
Interuniversity Centre for Research on Cognitive Processing in Natural and Artificial Systems (ECONA), IT, Rome, Italy.