Imaging the living brain, searching for telltale molecules in the cerebrospinal fluid, and measuring memory and thinking skills—these are among the tests scientists use to figure out who might eventually develop Alzheimer’s disease (AD). But what about asking a simple question: “How do you feel?” In an age of advanced technologies, this may seem a rudimentary way to predict disease, but a number of recent studies claim that a person’s own perception of health is as good an omen as any of future dementia. The latest evidence to bolster this claim appears in the October 5 Neurology online by researchers for the Three-City (3C) Study in France.

The 3C study observes community residents 65 and older from Bordeaux, Dijon, and Montpellier to determine the influence of various factors on the risk of dementia. By asking the 8,169 participants to rate their health and then following them for up to eight years, researchers led by Christophe Tzourio of the Hopital de la Salpêtrière, Paris, found that people who rated their health as poor were more likely to develop dementia than those who rated it fair, and even more so than those who felt they were in good health. Two earlier papers also pointed to a connection between people’s health ratings and dementia (Weisen et al., 1999; Yip et al., 2006), but this latest study is the largest.

“This study suggests that there is some value in asking people not just about specific medical conditions, but also more generally about their overall perception of wellness,” wrote Murali Doraiswamy at Duke University, Durham, North Carolina, in an e-mail to ARF. “It sends the message that we should treat the person, not the disease; i.e., we need to pay more attention to asking people about their feelings rather than just relying on what the biomarker tests show.” That is not to say that asking people how they feel can replace objective tests or will be enough to make a diagnosis or prescribe a medication. Rather, it should be something of which doctors take note, suggested Tzourio. “A doctor should ask this very natural question, ‘How would you rate your health?’ If a person rates it poorly and there is no obvious medical reason for saying that, and the patient is not depressed, then maybe [he or she] should be followed more closely for possible signs of dementia in later years,” he said.

None of the people recruited to the 3C study had a severe disease, such as cancer or diabetes. Some 5 percent rated their health as very poor or poor, 35 percent as fair, and 60.3 percent as good or excellent. After about eight years, 618 people in the study had dementia—either AD (68 percent), vascular dementia (7 percent), or other types (25 percent). Controlling for known dementia risk factors such as little education, a history of depression, or previous complaints with memory or thinking, the researchers determined that the risk of dementia was 70 percent higher in people who had rated their health as poor and 34 percent higher in people who rated it as fair, than in those who had considered their health good. “At first, we thought it was possible that people rated their health as bad because they were depressed, and the depression was what put them at higher risk for dementia, but instead we found that the relation between self-reported health and dementia remained, even in people without depression,” said Tzourio.

The association emerged in people without any earlier memory complaints or thinking problems; they were twice as likely to develop dementia if they had rated their health as poor than if they had said it was good. “Right now, if people tell their doctor that they are having problems remembering things, that is taken as a possible warning sign of dementia [that warrants further testing],” said Tzourio. “The same should be true of poor general health.”

Researchers are beginning to realize that age-related health factors not normally associated with AD may predict dementia independently of more established and specific ones, such as depression or memory complaint (see ARF related news story on Song et al., 2011 and Holmes et al., 2011). “Self-reported health is not a traditional risk factor for dementia. It is very nonspecific. It says that several years before patients have overt symptoms of dementia, they know something is wrong,” said Deborah Barnes at the University of California, San Francisco, who was not involved in the 3C study. “Nonspecific predictors can be useful, especially when other predictors are not present,” added Barnes, who has been incorporating health-related questions and biomarkers to develop a tool for predicting dementia risk (Barnes and Yaffe, 2009).

Because people’s own assessment of their health is such a “fuzzy” measurement, it is hard to say what it means in terms of dementia development and why there would be a connection between the two. One possibility, said Tzourio, is that if people have memory problems, an early sign of dementia, they might not recognize them as such, but rather say they are not feeling well. Another possibility is that people who say they don’t feel well end up going out less to socialize with others or to exercise; this might put them at higher risk for developing dementia (see ARF related news story).

Clive Holmes at the University of Southampton, U.K., favors yet another explanation. His work has shown that people with AD have higher levels of proinflammatory cytokines, and that these cytokines predict faster cognitive decline in AD patients (Holmes et al., 2009). “In this study they looked at a generalized feeling. My hypothesis is that what they are picking up is systemic inflammation, which makes people feel unwell,” said Holmes. Chronic inflammation is a known risk factor for AD (see ARF related news story), and a number of genes involved in inflammation are in the Top 10 AlzGene list.—Laura Bonetta


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News Citations

  1. Alzheimer’s Risk Factors Roundup: Does Poor Health Hurt the Brain?
  2. Exercise Helps Mouse Elders Learn, Generate New Neurons
  3. Australia Report: Inflammation

Paper Citations

  1. . Self-rated health assessment and development of both cardiovascular and dementing illnesses in an ambulatory elderly population: a report from the Bronx Longitudinal Aging Study. Heart Dis. 1999 Sep-Oct;1(4):201-5. PubMed.
  2. . Risk factors for incident dementia in England and Wales: The Medical Research Council Cognitive Function and Ageing Study. A population-based nested case-control study. Age Ageing. 2006 Mar;35(2):154-60. PubMed.
  3. . Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology. 2011 Jul 19;77(3):227-34. PubMed.
  4. . Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology. 2011 Jul 19;77(3):212-8. PubMed.
  5. . Predicting dementia: role of dementia risk indices. Future Neurol. 2009 Sep 1;4(5):555-560. PubMed.
  6. . Systemic inflammation and disease progression in Alzheimer disease. Neurology. 2009 Sep 8;73(10):768-74. PubMed.

External Citations

  1. Three-City (3C) Study
  2. Top 10 AlzGene list

Further Reading

Primary Papers

  1. . Self-rated health and risk of incident dementia: a community-based elderly cohort, the 3C study. Neurology. 2011 Oct 11;77(15):1457-64. PubMed.