ORLANDO – Up to half of all cases of Alzheimer’s disease are attributable to seven modifiable risk factors – including depression, Dr. Kristine Yaffe asserted in her 2014 AAGP Distinguished Scientist Award Lecture.
In addition to depression, the modifiable risk factors for Alzheimer's disease backed by the best supporting evidence from observational studies are diabetes, smoking, midlife obesity, midlife hypertension, low educational attainment, and physical inactivity.
A public health campaign successful in achieving a rather modest 10% reduction across the board in these seven risk factors could prevent an estimated 184,000 cases of Alzheimer's disease in the United States alone. A more ambitious 25% reduction in the levels of these seven risk factors could prevent close to half a million cases in the United States and 3 million worldwide, she predicted at the annual meeting of the American Association for Geriatric Psychiatry.
Dr. Kristine Yaffe
"We’re all told by the Alzheimer’s Association and others that there’s an epidemic in dementia. And it’s true: There is an epidemic in dementia, because we’re living longer and the baby boomers are aging. We’re seeing things we didn’t see before. There wasn’t so much neurodegenerative disease when people died in their 60s and 70s. Now that we’re living into our 80s and 90s, we’re going to see a lot more neurodegenerative disease. But there are also a lot of interesting secular trends that hold promise. I think we have reason to be cautiously optimistic," declared Dr. Yaffe, professor of psychiatry, neurology, and epidemiology at the University of California, San Francisco. She is also Roy and Marie Scola Endowed Chair in Psychiatry at UCSF, and is chief of geriatric psychiatry and director of the memory disorders clinic at the San Francisco Veterans Affairs Medical Center
Dr. Yaffe is credited with having played a pivotal role in establishing many of these risk factors, including, for example, depression (Arch. Gen. Psychiatry 2012;69:493-8), limited educational attainment, or literacy (J. Gerontol. A. Biol. Sci. Med. Sci. 2013 [doi:10.1093/gerona/glt176]), and cardiorespiratory fitness as a protective factor (Neurology 2014;82:1339-46) and J. Gerontol. A. Biol. Sci. Med. Sci. 2014 [doi:10.1093/gerona/glt287]).
She has also been a leader in identifying posttraumatic stress disorder and traumatic brain injury as risk factors, although those didn’t crack her list of key risks. Her interest in developing a preventive approach targeting modifiable risk factors amenable to a public health campaign has been fueled by recognition that Alzheimer’s disease is irreversible, slow to develop, and that existing drugs are of only limited symptomatic benefit and don’t halt disease progression.
She and coinvestigator Deborah E. Barnes, Ph.D., estimated the impact of reducing levels of the risk factors both in the United States and globally by first calculating the population-attributable risk; that is, the percentage of Alzheimer’s disease cases attributable to a given risk factor. They found that, globally, lack of education and smoking are the biggest contributors to risk. In the United States, physical inactivity contributed to the biggest proportion of cases (Lancet Neurol. 2011;10:819-28).
The current favored hypothesis as to how higher educational attainment, mental stimulation, physical exercise, and other factors protect against development of Alzheimer’s disease and other forms of dementia involves what’s called "cognitive reserve." Cognitive reserve is conceptualized as a sort of buffer in the brain that protects against neuropathologic accumulation. It’s what enables many seniors to have died with the normal cognitive function despite meeting neuropathologic criteria for Alzheimer’s disease at autopsy.
Dr. Yaffe draws hope from the well-documented marked decline in deaths from heart disease and stroke in recent decades, about half of which is attributable to treatment advances and the other half to public health measures aimed at risk factor reduction.
Evidence from recent studies suggests that a parallel decline in the incidence of dementia has been underway during the past couple of decades. For example, a population-based U.S. survey found the prevalence of cognitive impairment among people aged 70 years and older fell from 12.2% in 1993 to 8.7% in 2002 (Alzheimer's Dement. 2008;4:134-44). Dutch investigators reported that in the Rotterdam Study, the incidence rate ratio of dementia fell from 6.56 cases/1,000 person-years in 1990 to 4.92 cases/1,000 person-years in 2000 (Neurology 2012;78:1456-63). In three regions of England under study, the prevalence of dementia declined from 8.3% in 1989-1994 to 6.5% in 2008-2011 (Lancet 2013;382:1405-12). And, in Stockholm, there is evidence to suggest a decreasing incidence of dementia during a recent 20-year period (Neurology 2013;80:1888-94).
The authors of these studies attributed their findings to higher educational level, a decline in stroke incidence, and adoption of healthier lifestyles.