Vegetables and fruit provide a significant part of human nutrition, as they are important sources of nutrients, dietary fibre, and phytochemicals. However, it is uncertain whether the risk of certain chronic diseases can be reduced by increased consumption of vegetables or fruit by the general public, and what strength of evidence has to be allocated to such an association. Therefore, a comprehensive analysis of the studies available in the literature and the respective study results has been performed and evaluated regarding obesity, type 2 diabetes mellitus, hypertension, coronary heart disease (CHD), stroke, cancer, chronic inflammatory bowel disease (IBD), rheumatoid arthritis (RA), chronic obstructive pulmonary disease (COPD), asthma, osteoporosis, eye diseases, and dementia. For judgement, the strength of evidence for a risk association, the level of evidence, and the number of studies were considered, the quality of the studies and their estimated relevance based on study design and size. For hypertension, CHD, and stroke, there is convincing evidence that increasing the consumption of vegetables and fruit reduces the risk of disease. There is probable evidence that the risk of cancer in general is inversely associated with the consumption of vegetables and fruit. In addition, there is possible evidence that an increased consumption of vegetables and fruit may prevent body weight gain. As overweight is the most important risk factor for type 2 diabetes mellitus, an increased consumption of vegetables and fruit therefore might indirectly reduces the incidence of type 2 diabetes mellitus. Independent of overweight, there is probable evidence that there is no influence of increased consumption on the risk of type 2 diabetes mellitus. There is possible evidence that increasing the consumption of vegetables and fruit lowers the risk of certain eye diseases, dementia and the risk of osteoporosis. Likewise, current data on asthma, COPD, and RA indicate that an increase in vegetable and fruit consumption may contribute to the prevention of these diseases. For IBD, glaucoma, and diabetic retinopathy, there was insufficient evidence regarding an association with the consumption of vegetables and fruit. This critical review on the associations between the intake of vegetables and fruit and the risk of several chronic diseases shows that a high daily intake of these foods promotes health. Therefore, from a scientific point of view, national campaigns to increase vegetable and fruit consumption are justified. The promotion of vegetable and fruit consumption by nutrition and health policies is a preferable strategy to decrease the burden of several chronic diseases in Western societies.

/pdf/critical-review-vegetables-and-fruit-in-the-prevention-of-1xwi79ttv4.pdf

Critical review: vegetables and fruit in the prevention of chronic diseases

ContextObservational studies have suggested that postmenopausal hormone treatment
may improve cognitive function, but data from randomized clinical trials have
been sparse and inconclusive The Women's Health Initiative Memory Study (WHIMS)
is an ancillary study of the Women's Health Initiative (WHI) hormone therapy
trials On July 8, 2002, the estrogen plus progestin therapy in the WHI trial
was discontinued because of certain increased health risks for womenObjectiveTo determine whether estrogen plus progestin therapy protects global
cognitive function in older postmenopausal womenDesign, Setting, and ParticipantsA randomized, double-blind, placebo-controlled clinical trial, WHIMS
is an ancillary study of geographically diverse, community-dwelling women
aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen
plus progestin trial that started in June 1995 Of 4894 eligible postmenopausal
women aged 65 years or older and free of probable dementia at baseline, 4532
(926%) were enrolled in the estrogen plus progestin component of WHIMS A
total of 4381 participants (967%) provided at least 1 valid cognitive function
score between June 1995 and July 8, 2002InterventionsParticipants received either 1 daily tablet containing 0625 mg of conjugated
equine estrogen with 25 mg of medroxyprogesterone acetate (n = 2145) or matching
placebo (n = 2236)Main Outcome MeasureGlobal cognitive function measured annually with the Modified Mini-Mental
State ExaminationResultsThe Modified Mini-Mental State Examination mean total scores in both
groups increased slightly over time (mean follow-up of 42 years) Women in
the estrogen plus progestin group had smaller average increases in total scores
compared with women receiving placebo (P = 03),
but these differences were not clinically important Removing women by censoring
them after adjudicated dementia, mild cognitive impairment, or stroke, and
nonadherence to study protocol, did not alter the findings Prior hormone
therapy use and duration of prior use did not affect the interpretation of
the results, nor did timing of prior hormone therapy initiation with respect
to the final menstrual period More women in the estrogen plus progestin group
had a substantial and clinically important decline (≥2 SDs) in Modified
Mini-Mental State Examination total score (67%) compared with the placebo
group (48%) (P = 008)ConclusionsAmong postmenopausal women aged 65 years or older, estrogen plus progestin
did not improve cognitive function when compared with placebo While most
women receiving estrogen plus progestin did not experience clinically relevant
adverse effects on cognition compared with placebo, a small increased risk
of clinically meaningful cognitive decline occurred in the estrogen plus progestin
group

https://jamanetwork.com/journals/jama/articlepdf/196627/JOC30764.pdf

Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.

ContextThe Women's Health Initiative Memory Study (WHIMS) previously reported
that estrogen plus progestin therapy does not protect cognition among women
aged 65 years or older. The effect of estrogen-alone therapy, also evaluated
in WHIMS, on cognition has not been established for this population.ObjectivesTo determine whether conjugated equine estrogen (CEE) alters global
cognitive function in older women and to compare its effect with CEE plus
medroxyprogesterone acetate (CEE plus MPA).Design, Setting, and ParticipantsA randomized, double-blind, placebo-controlled ancillary study of the
Women's Health Initiative (WHI), WHIMS evaluated the effect of CEE on incidence
of probable dementia among community-dwelling women aged 65 to 79 years with
prior hysterectomy from 39 US academic centers that started in June 1995.
Of 3200 eligible women free of probable dementia enrolled in the WHI, 2947
(92.1%) were enrolled in WHIMS. Analyses were conducted on the 2808 women
(95.3%) with a baseline and at least 1 follow-up measure of global cognitive
function before the trial's termination on February 29, 2004.InterventionsParticipants received 1 daily tablet containing either 0.625 mg of CEE
(n = 1387) or matching placebo (n = 1421).Main Outcome MeasureGlobal cognitive function measured annually with the Modified Mini-Mental
State Examination (3MSE).ResultsDuring a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26
(0.13) units lower than among women assigned to CEE compared with placebo
(P = .04). For pooled hormone therapy (CEE combined
with CEE plus MPA), the mean (SE) decrease was 0.21 (0.08; P = .006). Removing women with dementia, mild cognitive impairment,
or stroke from the analyses lessened these differences. The adverse effect
of hormone therapy was more pronounced among women with lower cognitive function
at baseline (all P<.01). For women assigned to
CEE compared with placebo, the relative risk of having a 10-unit decrease
in 3MSE scores (>2 SDs) was estimated to be 1.47 (95% confidence interval,
1.04-2.07).ConclusionFor women aged 65 years or older, hormone therapy had an adverse effect
on cognition, which was greater among women with lower cognitive function
at initiation of treatment.

https://jamanetwork.com/journals/jama/articlepdf/198995/JOC41174.pdf

Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study.

Based on an evidence review conducted to support the National Institutes of Health's State-of-the-Science Conference, this systematic review summarizes evidence about putative risk and protective f...

https://sites.oxy.edu/clint/physio/article/SystematicReviewFactorsAssociatedWithRiskforandPossiblePreventionofCognitiveDeclineinLaterLife.pdf

Systematic review: factors associated with risk for and possible prevention of cognitive decline in later life.

Background
Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005.

Objectives
To assess effects of long-term HT (at least 1 year's duration) on mortality, cardiovascular outcomes, cancer, gallbladder disease, fracture and cognition in perimenopausal and postmenopausal women during and after cessation of treatment.

Search methods
We searched the following databases to September 2016: Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO. We searched the registers of ongoing trials and reference lists provided in previous studies and systematic reviews.

Selection criteria
We included randomised double-blinded studies of HT versus placebo, taken for at least 1 year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via the oral, transdermal, subcutaneous or intranasal route.

Data collection and analysis
Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the quality of the evidence by using GRADE methods.

Main results
We included 22 studies involving 43,637 women. We derived nearly 70% of the data from two well-conducted studies (HERS 1998; WHI 1998). Most participants were postmenopausal American women with at least some degree of comorbidity, and mean participant age in most studies was over 60 years. None of the studies focused on perimenopausal women.

In relatively healthy postmenopausal women (i.e. generally fit, without overt disease), combined continuous HT increased the risk of a coronary event (after 1 year's use: from 2 per 1000 to between 3 and 7 per 1000), venous thromboembolism (after 1 year's use: from 2 per 1000 to between 4 and 11 per 1000), stroke (after 3 years' use: from 6 per 1000 to between 6 and 12 per 1000), breast cancer (after 5.6 years' use: from 19 per 1000 to between 20 and 30 per 1000), gallbladder disease (after 5.6 years' use: from 27 per 1000 to between 38 and 60 per 1000) and death from lung cancer (after 5.6 years' use plus 2.4 years' additional follow-up: from 5 per 1000 to between 6 and 13 per 1000).

Oestrogen-only HT increased the risk of venous thromboembolism (after 1 to 2 years' use: from 2 per 1000 to 2 to 10 per 1000; after 7 years' use: from 16 per 1000 to 16 to 28 per 1000), stroke (after 7 years' use: from 24 per 1000 to between 25 and 40 per 1000) and gallbladder disease (after 7 years' use: from 27 per 1000 to between 38 and 60 per 1000) but reduced the risk of breast cancer (after 7 years' use: from 25 per 1000 to between 15 and 25 per 1000) and clinical fracture (after 7 years' use: from 141 per 1000 to between 92 and 113 per 1000) and did not increase the risk of coronary events at any follow-up time.

Women over 65 years of age who were relatively healthy and taking continuous combined HT showed an increase in the incidence of dementia (after 4 years' use: from 9 per 1000 to 11 to 30 per 1000). Among women with cardiovascular disease, use of combined continuous HT significantly increased the risk of venous thromboembolism (at 1 year's use: from 3 per 1000 to between 3 and 29 per 1000). Women taking HT had a significantly decreased incidence of fracture with long-term use.

Risk of fracture was the only outcome for which strong evidence showed clinical benefit derived from HT (after 5.6 years' use of combined HT: from 111 per 1000 to between 79 and 96 per 1000; after 7.1 years' use of oestrogen-only HT: from 141 per 1000 to between 92 and 113 per 1000). Researchers found no strong evidence that HT has a clinically meaningful impact on the incidence of colorectal cancer.

One trial analysed subgroups of 2839 relatively healthy women 50 to 59 years of age who were taking combined continuous HT and 1637 who were taking oestrogen-only HT versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT: Their absolute risk remained low, at less than 1/500. However, other differences in risk cannot be excluded, as this study was not designed to have the power to detect differences between groups of women within 10 years of menopause.

For most studies, risk of bias was low in most domains. The overall quality of evidence for the main comparisons was moderate. The main limitation in the quality of evidence was that only about 30% of women were 50 to 59 years old at baseline, which is the age at which women are most likely to consider HT for vasomotor symptoms.

Authors' conclusions
Women with intolerable menopausal symptoms may wish to weigh the benefits of symptom relief against the small absolute risk of harm arising from short-term use of low-dose HT, provided they do not have specific contraindications. HT may be unsuitable for some women, including those at increased risk of cardiovascular disease, increased risk of thromboembolic disease (such as those with obesity or a history of venous thrombosis) or increased risk of some types of cancer (such as breast cancer, in women with a uterus). The risk of endometrial cancer among women with a uterus taking oestrogen-only HT is well documented.

HT is not indicated for primary or secondary prevention of cardiovascular disease or dementia, nor for prevention of deterioration of cognitive function in postmenopausal women. Although HT is considered effective for the prevention of postmenopausal osteoporosis, it is generally recommended as an option only for women at significant risk for whom non-oestrogen therapies are unsuitable. Data are insufficient for assessment of the risk of long-term HT use in perimenopausal women and in postmenopausal women younger than 50 years of age.

Long term hormone therapy for perimenopausal and postmenopausal women

Background
As estrogens have been found in animal models to be associated with the maintenance and protection of brain structures, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by medication could be protective against cognitive decline.

Objectives
To investigate the effect of ERT (estrogens only) or HRT (estrogens combined with a progestagen) in comparison with placebo in randomized controlled trials (RCTs) on cognitive function in postmenopausal women.

Search strategy
The CDCIG Specialized Register was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* on 16 May 2002. In addition MEDLINE (1966-2002/01); EMBASE (1985-2000/11); PsycINFO (1967-2002/01) and CINAHL (1982-2001/12) were searched as the CDCIG Register does not contain all trials with healthy volunteers.

Selection criteria
All double-blind randomized controlled trials of the effect of ERT or HRT on cognitive function over a treatment period of at least two weeks in postmenopausal women.

Data collection and analysis
Abstracts of the references retrieved by the searches were read by two reviewers in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the resulting lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. Two reviewers (EH and KY) assessed the quality of other aspects including design and assessment of outcomes. One reviewer (EH) extracted the data from the studies.

Main results
In total, 15 trials involving 566 postmenopausal women were included, but 6 studies did not have adequate data for analysis. Meta-analyses showed a positive effect of 10 mg of estradiol (E2) bolus injections intramuscularly monthly in relatively young surgically menopausal women on the Paired Associate learning test immediate recall (z=2.40, p<0.05, chi-square test=1.12, p=0.29, SMD=1.02, 95% C.I.=0.19-1.85), on a test of abstract reasoning (z=10.45, p<0.0001, WMD=6.80, 95% C.I.=5.52-8.08) and a test of speed and accuracy (z=9.16, p<0.0001 WMD=6.00, 95% C.I.=4.72-7.28). However, most studies showed no evidence of an effect on verbal or visuospatial memory, mental rotations, speed or accuracy measures. There was little evidence that Premarin, the most widely prescribed estrogen for postmenopausal use, had positive effects on cognitive function. The one effect of 9 months of treatment with Premarin (and a progestagen) on a measure of complex speed of information processing (the TMT-B) was probably explained by baseline differences, as it was not reported by the authors.

Authors' conclusions
There was little evidence regarding the effect HRT or ERT on overall cognitive function in healthy postmenopausal women. There was an effect on some verbal memory functions (immediate recall), on a test of abstract reasoning and a test of speed and accuracy in relatively young (47 years of age) surgically menopausal women who had been given a bolus intramuscular injection of 10 mg E2 every month for 3 months. These effects were from small studies from a single research group. It remains to be determined whether factors such as an older age (> 69 years of age), type of menopause (surgical or natural) and type of treatment (E2 with or without a progestagen), mode of delivery (transdermal, oral or intramuscular), dosage and duration (> 3 months) could alter the effect on memory functions to a clinically relevant level. In addition, whether the absence or presence of menopausal symptoms can modify treatment effects should be investigated in more detail. Longitudinal RCTs currently underway in the U.S.A., U.K. and Canada will be able to test these hypotheses by the year 2010.

/pdf/hormone-replacement-therapy-for-cognitive-function-in-4kcecsx99y.pdf

Hormone replacement therapy for cognitive function in postmenopausal women.

BACKGROUND: As estrogens have been found in animal models to be associated with the maintenance and protection of brain structures, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by medication could be protective against cognitive decline. OBJECTIVES: To investigate the effect of ERT (estrogens only) or HRT (estrogens combined with a progestagen) in comparison with placebo in RCTs on cognitive function in postmenopausal women. SEARCH STRATEGY: The CDCIG Specialized Register was searched 7 March 2006. Additional searches were made of MEDLINE (1966-2006/02); EMBASE (1985-2006/02); PsycINFO (1967-2006/02) and CINAHL (1982-2006/01). SELECTION CRITERIA: All double-blind RCTs trials of the effect of ERT or HRT on cognitive function over a treatment period of at least two weeks in postmenopausal women. DATA COLLECTION AND ANALYSIS: Selection of studies, assessment of quality and extraction of data were undertaken independently by three reviewers with disagreements resolved by discussion. MAIN RESULTS: In total, 24 trials were included, but only 16 (10,114 women) had analysable data. Meta-analyses showed no effects of either ERT or HRT on prevention of cognitive impairment after five and four years of treatment, respectively (odds ratio 1.34, 95% CI 0.95 to 1.9; odds ratio 1.05, 95% CI 0.72 to 1.54 respectively) (trend favouring control in both instances). Analyses assessing the effects of treatment over time found that both ERT and HRT did not maintain or improve cognitive function and may even adversely affect this outcome (WMD = -0.45, 95% CI -0.99 to 0.09; WMD = -0.16, 95% CI -0.58 to 0.26, respectively at maximum follow up). Negative effects were found for ERT after one year and HRT after three and four years of therapy. Results from smaller trials assessing effects on individual cognitive domains mostly reported no evidence of benefit. AUTHORS' CONCLUSIONS: There is good evidence that both ERT and HRT do not prevent cognitive decline in older postmenopausal women when given as short term or longer term (up to five years) therapy. It is not known whether either specific types of ERT or HRT have specific effects in subgroups of women, although there was evidence that combined hormone therapy in similarly aged women was associated with a decrement in a number of verbal memory tests and a small improvement in a test of figural memory. There is insufficient evidence to determine whether subgroups of women using specific types of hormone therapy could benefit from treatment. It remains to be determined whether factors such as younger age (< 60 years of age), type of menopause (surgical or natural) and type of treatment (type of estrogen with or without a progestagen), mode of delivery (transdermal, oral or intramuscular) and dosage have positive effects at a clinically relevant level. In addition, whether the absence or presence of menopausal symptoms can modify treatment effects should be investigated in more detail. Large RCTs currently underway in the USA may be able to provide answers to these uncertainties by the year 2010. In the meantime, based on the available evidence, ERT or HRT cannot be recommended for overall cognitive improvement or maintenance in older postmenopausal women without cognitive impairment.

Background/Aims: Cell culture studies suggest that phytoestrogens, abundant in soy products such as tempe and tofu, could protect against cognitive decline. Paradoxically, the Honol

High Tofu Intake Is Associated with Worse Memory in Elderly Indonesian Men and Women

As we age, most of us experience a certain degree of cognitive decline. In most cases, this decline is gradual. However, in some cases, cognitive impairment is so severe that it can be classified as dementia and this impacts greatly on activities of daily living. Alzheimer's disease, the most common form of dementia, has been linked to the reduction in estrogen levels that comes with aging. More specifically, many researchers have hypothesized that estrogen, and hence estrogen replacement via hormone therapy, could protect against cognitive decline in women. However, recent randomized, controlled trials did not reflect this. In fact, some reports showed that hormone therapy could have detrimental effects on cognitive function in older postmenopausal women. The most publicized of these has been the Women's Health Initiative Memory Study. Studies have thus yielded conflicting results and conclusions. The reasons for this may be due to a number of factors, such as the age of participants, the time of hormone therapy onset ('window of opportunity' theory), type of treatment, type of menopause (surgical or natural) and, possibly, genetic risk factors. We performed quantitative and qualitative meta-analyses and reviewed each of these factors in detail. The future may lie in combining these factors in order to fully understand the potential mechanisms behind estrogen and its effect on cognition.

https://journals.sagepub.com/doi/pdf/10.2217/17455057.3.2.173

Amina Yesufu

Papers

Hormone replacement therapy for cognitive function in postmenopausal women.

Hormone replacement therapy for cognitive function in postmenopausal women.

High Tofu Intake Is Associated with Worse Memory in Elderly Indonesian Men and Women

Meta-analyses of the effect of hormone treatment on cognitive function in postmenopausal women.

Different forms of soy processing may determine the positive or negative impact on cognitive function of Indonesian elderly