Background and Purpose—This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment ...

Vascular Contributions to Cognitive Impairment and Dementia A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Polyphenols are the most abundant antioxidants in the diet and are widespread constituents of fruits, vegetables, cereals, dry legumes, chocolate, and beverages, such as tea, coffee, or wine. Experimental studies on animals or cultured human cell lines support a role of polyphenols in the prevention of cardiovascular diseases, cancers, neurodegenerative diseases, diabetes, or osteoporosis. However, it is very difficult to predict from these results the effects of polyphenol intake on disease prevention in humans. One of the reasons is that these studies have often been conducted at doses or concentrations far beyond those documented in humans. The few clinical studies on biomarkers of oxidative stress, cardiovascular disease risk factors, and tumor or bone resorption biomarkers have often led to contradictory results. Epidemiological studies have repeatedly shown an inverse association between the risk of myocardial infarction and the consumption of tea and wine or the intake level of some particular flavonoids, but no clear associations have been found between cancer risk and polyphenol consumption. More human studies are needed to provide clear evidence of their health protective effects and to better evaluate the risks possibly resulting from too high a polyphenol consumption.

Dietary polyphenols and the prevention of diseases

The relation between diabetes and major types of dementia is controversial. This systematic review examines the incidence of dementia in people with diabetes mellitus. We identified 14 eligible longitudinal population-based studies of variable methodological quality. The incidence of "any dementia" was higher in individuals with diabetes than in those without diabetes in seven of ten studies reporting this aggregate outcome. This high risk included both Alzheimer's disease and vascular dementia (eight of 13 studies and six of nine studies respectively). Detailed data on modulating and mediating effects of glycaemic control, microvascular complications, and comorbidity (eg, hypertension and stroke) were generally absent. The findings of mechanistic studies suggest that vascular disease and alterations in glucose, insulin, and amyloid metabolism underlie the pathophysiology, but which of these mechanisms are clinically relevant is unclear. Further high quality studies need to be initiated, with objective diabetes assessment, together with reliable methods to establish the contribution of vascular disease and other comorbidity to dementia.

Risk of dementia in diabetes mellitus: a systematic review

The recent availability of longitudinal data on the possible association of different lifestyles with dementia and Alzheimer's disease (AD) allow some preliminary conclusions on this topic. This review systematically analyses the published longitudinal studies exploring the effect of social network, physical leisure, and non-physical activity on cognition and dementia and then summarises the current evidence taking into account the limitations of the studies and the biological plausibility. For all three lifestyle components (social, mental, and physical), a beneficial effect on cognition and a protective effect against dementia are suggested. The three components seem to have common pathways, rather than specific mechanisms, which might converge within three major aetiological hypotheses for dementia and AD: the cognitive reserve hypothesis, the vascular hypothesis, and the stress hypothesis. Taking into account the accumulated evidence and the biological plausibility of these hypotheses, we conclude that an active and socially integrated lifestyle in late life protects against dementia and AD. Further research is necessary to better define the mechanisms of these associations and better delineate preventive and therapeutic strategies.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474442204007677.pdf

An active and socially integrated lifestyle in late life might protect against dementia.

The global prevalence of dementia is estimated to be as high as 24 million, and is predicted to double every 20 years through to 2040, leading to a costly burden of disease. Alzheimer disease (AD) is the leading cause of dementia and is characterized by a progressive decline in cognitive function, which typically begins with deterioration in memory. Before death, individuals with this disorder have usually become dependent on caregivers. The neuropathological hallmarks of the AD brain are diffuse and neuritic extracellular amyloid plaques-which are frequently surrounded by dystrophic neurites-and intracellular neurofibrillary tangles. These hallmark pathologies are often accompanied by the presence of reactive microgliosis and the loss of neurons, white matter and synapses. The etiological mechanisms underlying the neuropathological changes in AD remain unclear, but are probably affected by both environmental and genetic factors. Here, we provide an overview of the criteria used in the diagnosis of AD, highlighting how this disease is related to, but distinct from, normal aging. We also summarize current information relating to AD prevalence, incidence and risk factors, and review the biomarkers that may be used for risk assessment and in diagnosis.

/pdf/epidemiology-of-alzheimer-disease-4jbouco1i1.pdf

Epidemiology of Alzheimer disease

A prospective analysis of risk factors for Alzheimer's disease was a major objective of the Canadian Study of Health and Aging, a nationwide, population-based study. Of 6,434 eligible subjects aged 65 years or older in 1991, 4,615 were alive in 1996 and participated in the follow-up study. All participants were cognitively normal in 1991 when they completed a risk factor questionnaire. Their cognitive status was reassessed 5 years later by using a similar two-phase procedure, including a screening interview, followed by a clinical examination when indicated. The analysis included 194 Alzheimer's disease cases and 3,894 cognitively normal controls. Increasing age, fewer years of education, and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer's disease. Use of nonsteroidal anti-inflammatory drugs, wine consumption, coffee consumption, and regular physical activity were associated with a reduced risk of Alzheimer's disease. No statistically significant association was found for family history of dementia, sex, history of depression, estrogen replacement therapy, head trauma, antiperspirant or antacid use, smoking, high blood pressure, heart disease, or stroke. The protective associations warrant further study. In particular, regular physical activity could be an important component of a preventive strategy against Alzheimer's disease and many other conditions.

http://sites.oxy.edu/clint/physio/article/RiskFactorsforAlzheimersDiseaseAProspectiveAnalysisfromtheCanadianStudyofHealthandAging.pdf

Risk Factors for Alzheimer’s Disease: A Prospective Analysis from the Canadian Study of Health and Aging

To study the role of commercial fishing and related factors in the development of lip cancer, a project that included a case–control study and a cohort analysis was undertaken in Newfoundland. Household survey data were linked with cancer-registry and census data. In comparison with other males, fishermen had a probability of development of lip cancer that was 1.5 times higher (by the case–control method, P < 0.05) or 4.4 times higher (by cohort analysis, P < 0.001 ). Despite the effect of pipe smoking, "outdoorness" and age on the development of lip cancer in general, the occupation of fishing was an additional, independent contribution to the risk. Unexpectedly, using the mouth as a third hand to handle tar-coated nets seemed to protect fishermen from the disease. It was not possible to attribute the higher risk to a particular work activity, nor was a specific responsible carcinogen identified. (N Engl J Med 293:419–424, 1975)

The Occupation of Fishing as a Risk Factor in Cancer of the Lip

Systematic errors occur in the reports of disease frequency derived from health surveys based on questionnaire interviews. Five hundred and thirty-three persons with clinically and histologically confirmed disease in a case-control study of cancer were interviewed in their homes by carefully trained interviewers using a standardized questionnaire interview schedule. Comparisons of the information obtained by interview about past history of cancer with cancer registry and hospital medical record information about the same people revealed serious underestimates of correct frequency and wide variation in the rates of correct reporting. The findings reported here and elsewhere add support to an essential requirement in medical survey research: the completeness and accuracy of responses in health interview surveys must be verified and the methods of verification must be reported before the results can be interpreted with confidence.

Barbara E. Helliwell

Papers

Risk Factors for Alzheimer’s Disease: A Prospective Analysis from the Canadian Study of Health and Aging

The Occupation of Fishing as a Risk Factor in Cancer of the Lip

Underreporting of cancer in medical surveys: a source of systematic error in cancer research