7 June 2012. The 12th International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy took place May 9-12 in the Swedish Capital. Organized by Agneta Nordberg, Karolinska Institute, Stockholm, and Ezio Giacobini and Gabriel Gold from the University of Geneva, Switzerland, this meeting had something for nearly everyone’s palate, from basic biology to preclinical drug discovery and on through to diagnostic and treatment strategies. In the plenary session, on the health challenges of AD for the 21st century, Laura Fratiglioni, from the Karolinska, addressed the question of whether the disease is preventable.

The answer is not clear, but, Fratiglioni reminded the audience that 40 percent of nonagenarians do not have dementia. Why? Looking through data from the Kungsholmen Project, a longitudinal, population-based study of aging that started in 1987, Fratiglioni found that about half of the people who develop dementia have one or more co-morbidities. They were less active, encumbered with higher cardiovascular disease burden, and were less well educated or involved in simpler work than those who remained dementia free. Acknowledging these well-studied risk factors, Fratiglioni said that tackling those could go a long way toward prevention (see ARF related news story). In fact, Fratiglioni hinted that the incidence of AD may be falling because people are now aging with less vascular disease than some years ago. Researchers at the meeting thought this could be a major shift. “The arguments are compelling and if true indicate a much bigger effect than you can imagine any drug to have,” Lon Schneider, University of Southern California, told Alzforum. While Schneider thinks it is plausible that age-specific incidence could be falling, he noted that data supporting the idea is still lacking. Fratiglioni told Alzforum that she plans to submit data from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K) project for publication soon.

Nevertheless, the world faces a growing dementia problem as life expectancy increases globally. Intervention studies have begun to test the idea that reducing risk factors can prevent dementia, noted Miia Kivipelto, also from the Karolinska. For example, the PreDiva—or Prevention of Dementia by Intensive Vascular Care trial —being run by Willem van Gool and colleagues at the University of Amsterdam, in the Netherlands, uses nurse intervention to limit vascular disease burden (see Richard et al., 2009). In France the Multidomain Alzheimer Preventive Trial or MAPT (see Gillette-Guyonnet et al., 2009) led by Bruno Vellas and colleagues at the University of Toulouse tests whether a dietary (omega 3 fatty acids) and/or a multidomain intervention that tackles metabolic and vascular risk factors can reduce dementia incidence.

For her part, Kivipelto summarized the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). This two-year study will test if a multidomain lifestyle intervention can reduce cognitive decline.

FINGER recruited 60-77 year-olds from a national population-based non-intervention study (FINRISK). The 1,200 people recruited receive placebo or an intervention covering four domains: nutrition; exercise; cognitive training; and monitoring and management of metabolic and cardiovascular risk factors. Control subjects receive advice but no intervention, said Kivipelto. The primary outcome for the trial is cognitive impairment assessed with the Neuropsychological Test Battery, and Stroop and Trail Making tests. Preliminary results from the first year of the trial that suggest the intervention reduces body weight and body-mass index, and lowers total and LDL-cholesterol. Oral glucose tolerance tests hint at a positive trend toward better metabolism. No cognitive data is available yet, Kivipelto said.

Kivipelto said that data from FINGER, PreDIVA and MAPT could serve as a basis for larger multinational trials. The Finnish, Dutch and French trials are already networking through the European Dementia Prevention Initiative, which was launched in April 2011 in Stockholm.

Can such intervention studies really reduce the risk of dementia? Kivipelto and others have devised risk scores for dementia based on modifiable factors such as high blood pressure, serum cholesterol, and obesity (see ARF related news). As Kivipelto suggested in her presentation, those scores suggest that a 50-year old male with a poor cardiovascular profile and a 16 percent risk of becoming demented by age 70 could quench his risk to seven percent by lowering serum cholesterol and blood pressure, and even to two percent by taking up exercise and losing weight. Only intervention studies can determine whether such predictions turn out to be true.—Tom Fagan.