The incidence of dementia and mild cognitive impairment can be decreased by removing risk factors such as diabetes and depression, according to a new prospective cohort study.
In addition, increasing crystallized intelligence (influenced by education and continual learning as an adult) and the consumption of fruits and vegetables seem to have a greater impact than modifying genetic risk. However, these factors are more difficult to implement as the levels of exposure to which they provide protective effects are unknown, note the researchers.
"These risk factors have been highlighted by previous epidemiological research, but this is the first study of comparative benefit, estimating the relative advantages of elimination of various risk factors," write lead study author Karen Ritchie, MD, senior research director at the French National Institute of Medical Research in Montpelier, France, and professor of neuroepidemiology at Imperial College London in the United Kingdom, and colleagues.
"Although causal relations cannot be concluded with certainty, [our] study suggests priorities that may inform public health programs," add the study authors. "Diabetes and perhaps also depression (on the assumption that causality can be established such that it is clearly shown to be a risk factor and not just a disease prodrome) should be the principal targets of future population-based health prevention programs.
"The clinical message is that from young adulthood, [we should] try to prevent patients from being exposed to insulin dependence before it becomes diabetes and treat depression when it appears — and not take it lightly," Dr. Ritchie told Medscape Medical News. In addition, "it may not be a cause of Alzheimer's disease, but associated inflammation and cortisol-related damage may [also] exacerbate underlying pathologies."
The study was published online August 5 in BMJ.
A Pandemic of Dementia
According to the researchers, dementia is predicted to increase by 100% between 2001 and 2020 in developed countries and by 300% during the same period in China, India, and other South Asian and Western Pacific countries.
"In the face of a pandemic of dementia, even small reductions in incidence, or delaying the age of onset, are likely to have significant effects on prevalence and the enormous associated public health burden," they write.
Although "multiple potentially modifiable clinical and environmental risk factors for dementia have been identified from [past] population studies ... interventional epidemiology has been relatively neglected," explain the study authors.
"Historically, even when we do not know the cause of a disease, we can reduce the numbers of new cases by identifying risk factors — that is, conditions which seem to increase the probability of becoming ill and then advising the public to avoid these risks," noted Dr. Ritchie. "But which risk factors should we target?"
For this study, the investigative team identified a list of common, potentially modifiable dementia risk factors and divided them into 3 groups: sociodemographic (including education and ethnic differences), clinical (including polymorphisms of the apolipoprotein E [ApoE] gene/ε4 allele, vascular factors, drug use, and a history of depression, asthma, and repeated exposure to herpes), and environmental and lifestyle (including cognitive activities, diet, consumption of alcohol and caffeine, and nicotine intake).
They then examined data from a cohort of 1433 participants in the Esprit study, a neuropsychiatric trial that enrolled patients between 1999 and 2001. These patients were all from Montpellier, France, and older than 65 years (mean ± SD baseline age, 72.5 ± 5.1 years).
The participants were examined by a neurologist to determine possible dementia and/or mild cognitive impairment at baseline and at 2, 4, and 7-year follow-up.
In addition, a standardized interview on sociodemographic and clinical factors, the Neale adult reading test (considered to be a measure of crystallized intelligence), and nutritional questionnaires were administered at all study periods. Blood pressure and blood samples were also taken.
Finally, depressive symptoms were assessed by the Center for Epidemiological Studies depression scale, and current major depressive episodes were diagnosed with the MINI neuropsychiatric examination.
Risk Factors Determined
At the end of the study, the researchers found 405 incident cases of dementia and/or mild cognitive impairment.
When the candidate risk factors were examined, significant associations of incidence were found for low education, crystallized intelligence (through the Neale adult reading test score, depression, stroke, diabetes, ApoE ε4 allele, ischemic heart disease, head injury, caffeine consumption, exposure to anesthesia, and fruit and vegetable consumption.
The final multivariate model retained crystallized intelligence, depression, ApoE ε4 allele, fruit and vegetable consumption, and diabetes.
Table. Significant Risk Factors for Dementia, Multivariate Model
| Factor | Population-Attributable Fraction (95% CI), % |
| Crystallized intelligence | 18.11 (10.91 – 25.42) |
| Depression | 10.31 (3.66 – 17.17) |
| ApoE ε4 allele | 7.11 (2.44 – 11.98) |
| Fruit and vegetable consumption | 6.46 (0.15 – 13.06) |
| Diabetes | 4.88 (1.87 – 7.98) |
CI = confidence interval
The study authors note that their analyses included treatment for depression and diabetes, noting that "although treatment may have eliminated symptoms and reduced risk through decreasing length of exposure, the person [was] exposed to all the underlying negative biological effects associated with the disease state that may be linked to the etiology of dementia, such as inflammation, increased permeability of the blood-brain barrier, damage to white matter, and raised cortisol concentrations.
"In this context, the corollary of our population attributable fraction analyses in terms of public health interventions is that these disorders should not so much be treated as prevented from occurring at all," summarize the study authors. "This would imply targeting and monitoring of people at high risk and introducing preventive treatment where feasible."
Highlights a Need
"This was a very interesting study that confirmed some of what is already known in the literature, which is that depression is associated with subsequent development of dementia — probably both Alzheimer's and vascular dementia," Wayne Katon, MD, professor and vice chair in the Department of Psychiatry and Behavioral Sciences at the University of Washington School of Medicine in Seattle, told Medscape Medical News.
"Also, multiple studies have shown that diabetes itself is a risk, particularly for vascular dementia but perhaps for Alzheimer's as well," added Dr. Katon, who recently performed a study of almost 4000 diabetics patients, showing that those with depression had a 2.7-fold higher risk of developing dementia than did those with diabetes alone. He was not involved with this study.
Dr. Katon noted that the unique part of this trial was "the wide range of variables" examined. "The strength of this study is that it's longitudinal and really has a more comprehensive list of both socioeconomic and clinical variables than do prior studies. Another strength was that [the investigators] tried, based on their findings, to determine where we should target our screenings and treatment for preventative programs.
"Overall, I'm impressed with this study," he said, but warned that he is concerned that "we're in the middle of a worldwide obesity epidemic.
"This means we're going to have a dramatic increase in the rate of type 2 diabetes over the next 5 to 20 years, which then means we're going to have significantly more rather than less dementia, if the findings in this article hold true. It's going to take a tremendous public health approach to decrease the rates of obesity and therefore type 2 diabetes. And I think studies like this can really help highlight this need," concluded Dr. Katon.
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