In the last few years, numerous studies have reported that dementia incidence is falling in the developed world. The drop in new cases has been attributed to better public health, in particular improved blood pressure control, but this conclusion may not tell the whole story. At the first Advances in Alzheimer’s and Parkinson’s Therapies Focus Meeting (AAT-AD/PD), held March 15–18 in Turin, Italy, Walter Rocca of the Mayo Clinic in Rochester, Minnesota, summarized recent research from his group and others that suggests the incidence of neurodegenerative diseases such as Parkinson’s, amyotrophic lateral sclerosis, and early onset Alzheimer’s is going up, not down. The reasons are unclear but could be environmental factors. Rocca argued this trend may extend to late-onset AD as well. He attributed the drop in all-cause dementia in recent decades to fewer cases of vascular dementia and stroke, which he thinks could be masking an increase in pure AD pathology.
- The incidence of PD, ALS, and early onset AD appears to be rising.
- The incidence of late-onset AD may be rising too.
- The drop in all-cause dementia is due to vascular health improvements.
Other data at AAT-AD/PD supported the related idea that vascular factors drive much of the risk of dementia in the very old. Claudia Kawas of the University of California, Irvine, reported findings from her 90+ study that found vascular disease conferred twice as much dementia risk in the oldest old as did having Alzheimer’s pathology. Together, the data highlight the role of vascular pathology in brain health, but also the need to distinguish between underlying biologic mechanisms of neurodegeneration, and to reduce risk factors behind each mechanism in order to improve public health.
Much has been made of studies in the U.S. and Europe that have found lower rates of dementia from about the year 1990 onward. The average drops about 25 percent over a decade in most studies (May 2013 news; Feb 2016 news; Nov 2016 news). Much of the improvement appears to stem from better cardiovascular health, although more education, less smoking, and other lifestyle changes have also been credited (Jul 2014 news; Apr 2016 news; Sep 2017 news). Importantly, these epidemiological studies did not distinguish between AD and other causes of dementia.
In Turin, Rocca warned that at the same time researchers are seeing these encouraging dementia trends, they are watching the incidence of parkinsonism rise. His group found that from 1976–2005 in Minnesota, the incidence in men increased by 30 percent (Jul 2016 news). Studies in Finland and Taiwan report similar numbers, with increases of 10 percent per decade (Isotalo et al., 2017; Liu et al., 2016). At the same time, new cases of ALS have climbed in Denmark (Seals et al., 2013).
Why is this happening? Scientists do not know. Epidemiological studies have found an inverse correlation between PD and cigarette smoking, smokeless tobacco use, and exposure to secondhand smoke, hinting that something in tobacco could be protective (Li et al., 2015; O’Reilly et al., 2005; Searles et al., 2012). If this is the case, falling smoking rates could be fueling a rise in PD, some researchers propose. For his part, Rocca mentioned head trauma, infectious agents, or alcohol consumption as possible culprits for the PD surge (Jul 2016 news; Dec 2016 news).
In particular, exposure to pollutants and pesticides has been implicated in Parkinson’s and ALS risk, and Rocca believes this may be the major reason for the increase he sees (Apr 2011 news; Lee et al., 2016; May 2016 news). Agricultural pesticide use surged after World War II, meaning more people now consume these substances in their diet, Rocca told Alzforum. Urban crowding and exposure to pollutants have also increased.
Could pollutants and pesticides bump up AD incidence as well? AD has been linked to pesticide exposure (Jan 2014 news), but evidence is scarce. One bit comes from a Canadian study, which reported a 24 percent rise in dementia in people between the ages of 50 and 64 from 2002–2013 (Cerasuolo et al., 2017). Since younger people with dementia typically develop a pure neurodegenerative pathology such as AD or frontotemporal dementia, without other age-related disorders or vascular pathology, this hints that AD could be climbing, Rocca said.
The drop in all-cause dementia seen epidemiologically could be explained simply by better cardiovascular health, Rocca suggested. Stroke and heart disease have been on the wane for up to 50 years, and Canadian researchers report drops of up to 40 percent in new cases since 2002 (Jones and Greene, 2013; Sposato et al., 2015). Stroke and vascular disease may account for a significant portion of dementia, Rocca said. One large neuropathological study of 5,715 brains in the National Alzheimer’s Coordinating Center database found signs of vascular disease in 60 percent to 80 percent of all dementia cases (Toledo et al., 2013).
In Turin, Kawas’ presentation bolstered Rocca’s view. Her 90+ study has 1,603 participants, 76 percent of whom are women. Their mean age is 96; one-third each are cognitively healthy, mildly impaired, or have dementia. So far, 309 have come to autopsy. Kawas reported that only 60 percent of participants with dementia had plaques and tangles, not much higher than the 42 percent of non-demented people who did. These non-demented people with high amyloid burden tended to have protective factors, such as an ApoE2 allele or high education, Kawas noted.
Overall, having AD pathology about doubled a very old person’s risk of having dementia, but other conditions conferred far more dementia risk. Vascular disease quadrupled it, Lewy body disease jacked up the odds sixfold, and hippocampal sclerosis 10-fold. In fact, hippocampal sclerosis accounted for one-third of dementia cases in this cohort. This condition correlated with having thyroid disease and thyroid antibodies in the blood, Kawas said. In the oldest old, pathologies other than AD account for much of the dementia risk, she concluded, estimating that eliminating AD pathology entirely would only halve the number of dementia cases in the oldest old.
“The dementia developing de novo in this group is very different in causes and manifestations from dementias with earlier onset,” Rocca noted. “This important work supports the hypothesis that improvements in cardiovascular health may be a major hope for the prevention of dementia.”
Will population dementia rates continue to fall? It’s hard to predict, Rocca said. Worsening obesity and diabetes may offset gains from better cardiovascular health, while factors such as pesticide use may drive an increase in pure neurodegeneration, he argues (Rocca, 2017). Even if incidence falls, prevalence will continue to rise worldwide due to the aging population and less access to healthcare and to higher education in the developing world (Aug 2015 news; Oct 2016 news; May 2017 news).
Rocca compared epidemiologic trends to a mobile blowing in the wind—a relatively small perturbation can cause it to flip around. “Disease risks change over historical epochs, and the trends reflect complex interactions. It’s a delicate balance,” he said.—Madolyn Bowman Rogers
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