Treating Heart Disease Risk Factors May Slow Alzheimer’s Disease Progression

Late-life weight loss and “motivational reserve” may also affect Alzheimer’s risk

Washington D.C., June 10, 2007

A new study suggests that treating risk factors for heart disease and stroke, such as high blood pressure and diabetes, may slow the progression of Alzheimer’s disease, according to research reported today at the 2nd Alzheimer’s Association International Conference on Prevention of Dementia in Washington, D.C.

Two new studies presented at the conference further confirm the close relationship between heart health and brain health. A third report, this one from the Nun Study, suggests that unexplained weight changes in late life have an impact on dementia risk and also may be useful, when combined with other factors such as biomarkers, as an indicator for early detection of dementia. Finally, a team of scientists has developed a new concept called “motivational reserve,” similar to “cognitive reserve,” that may be related to incidence and progression of Alzheimer’s.

“The best known and most solid risk factors for Alzheimer’s are age, family history and genetics, but those are things you can’t change,” said William Thies, Ph.D., vice president of Medical and Scientific Relations for the Alzheimer’s Association. “Research that identifies lifestyle risk factors gives people actions they can do, and positive choices they can make, to reduce their risk of Alzheimer’s – like lowering their blood pressure and treating their diabetes, or better still avoiding them in the first place. That’s a good research investment.”

Treating vascular risk factors may slow progression of Alzheimer’s

There is growing evidence that factors that increase the risk of vascular events like heart attack or stroke also increase the risk of cognitive decline; and that treatment of some vascular risk factors, such as use of blood pressure lowering medication, may reduce dementia occurrence.

Yan Deschaintre, M.D., F.R.C.P.(C), of the Centre Mémoire, Hôpital Roger Salengro, Lille, France and colleagues investigated whether vascular risk factors treatment slows cognitive decline once Alzheimer’s and/or vascular dementia is already evident.

The researchers analysed medical records of patients attending their memory clinic for the first time between 1997 and 2003 inclusively who had a final diagnosis of Alzhiemer’s, Alzhiemer’s with cerebro-vascular disease, or vascular dementia. Vascular risk factors sought were high blood pressure, diabetes,
dyslipidemia, and atherosclerotic vascular disease. The patients were considered treated if they received an antihypertensive, an oral antihyperglycemic or insulin, a statin or a fibrate, an antiplatelet, or an anticoagulant.

Among the 891 dementia patients studied, the researchers found that those who had their vascular risk factors treated declined less than those who had not. For people with Alzheimer’s without signs of vascular dementia, vascular risk factors treatment reduced yearly cognitive decline by almost one third, according to the mini-mental state evaluation (MMSE) score.

“That means the patients whose vascular risk factors were treated declined at a slower rate such that it took them three years to decline as much as untreated patients did after two years,” Deschaintre said.

“Most of the social and financial burden caused by Alzheimer’s and dementia is generated by the later, more severe stages of the disease,” Deschaintre said. “By slowing dementia progression, vascular risk factors treatment may delay the severe stages and have a significant impact on reducing the burden of dementia.”

Atherosclerosis surgery and stroke or TIA associated with increased risk of MCI

Carotid endarterectomy is performed when a major blood vessel that supplies blood to the brain is blocked as a result of atherosclerosis. Atherosclerosis in blood vessels in the brain reduces oxygen supply to the brain and could cause a stroke or a very mild stroke known as a transient ischemic attack (TIA).

Rosebud O. Roberts, M.B., Ch.B., and colleagues at the Mayo Clinic in Rochester, Minn., investigated whether people who have had a carotid endarterectomy or stroke are more likely to have an impairment in their memory and thinking skills known as mild cognitive impairment (MCI), which is in some cases a precursor to Alzheimer’s.

885 persons aged 70 to 89 in Olmsted County, Minn., received a comprehensive examination of memory and thinking skills, and were asked if they had ever had a carotid endarterectomy or a stroke or TIA. 295 persons in the study group were found to have MCI and were age and sex-matched to 590 controls (persons free of MCI).

Among those who had MCI, 13/295 (4.41%) reported having had a carotid endarterectomy, but only 12/590 (2.03%) of controls had this surgery. Similarly, 77 (26.1%) MCI cases reported having had a stroke or TIA compared to 83 (14.07%) controls.

“In this population, elderly subjects who have had a carotid endarterectomy or stroke or TIA are about two times more likely to have MCI,” Roberts said. “This may be due to the effects of the severe blockage of blood flow to the brain that made the surgery necessary, or to the effects of the stroke or TIA. Although carotid artery surgery could be associated with complications, an alternate explanation for our findings is that carotid artery surgery may be a marker for generalized atherosclerosis.”

Unexplained late-life weight loss may predict risk of dementia

Some studies have suggested that weight loss may be a predictor of incident Alzheimer’s disease. James Mortimer, Ph.D., Professor of Epidemiology and Biostatistics at the University of South Florida, Tampa, and Co-Principal Investigator of the Nun Study, and colleagues sought to determine whether there is an association of weight at baseline and rate of weight loss with the risk of developing dementia, and also whether there is an association of weight or weight loss with the severity of Alzheimer’s disease changes in the brain seen at autopsy.

537 non-demented Catholic sisters aged 75-102 who were participants in The Nun Study were followed for up to 10 years with annual clinical assessments and determinations of weight. In a subset of 363 Catholic sisters who died during the study, the associations of weight at baseline and the final weight before death with Alzheimer brain changes (as measured using Braak stages) were assessed. In the same group, age- and education-adjusted associations of baseline weight and final weight with the final MMSE score before death were evaluated.

Lower initial weight and higher rate of weight loss were significantly associated with an increased risk of developing dementia. Lower initial weight and lower final weight before death were significantly associated with more severe Alzheimer’s changes in the brain. Lower initial weight and final weight also were significantly associated with lower final MMSE score before death. However, when Braak stage was added to the latter model, the association of weight with the final MMSE score was lost.

“This is the first study to show that lower weight up to 10 years before death is specifically related to the severity of Alzheimer’s disease,” Mortimer said. “Given its very long duration prior to onset of dementia, it is likely that weight loss is specifically associated with the Alzheimer’s disease process and not to a restriction in food intake due to cognitive decline.”

“In addition, unexplained weight loss late in life coupled with other biomarkers may help to identify those at risk of Alzheimer’s more than a decade before symptoms start to show,” Mortimer said. “Identification of people who are at high risk of Alzheimer’s will be critical once agents become available that slow the disease course.”

“Motivational reserve” is a new concept complementing cognitive reserve

The idea of “cognitive reserve” is that the brains of people with high intelligence and superior education have greater resilience that enables them to cope better with the damage caused by Alzheimer’s disease, resulting in later onset of cognitive symptoms though more swift decline.

Simon Forstmeier, PhD, and Andreas Maercker, M.D., Ph.D., of the University of Zurich, Switzerland, and colleagues have developed and are investigating a complementary concept called “motivational reserve,” which suggests that qualities such as will power, self-discipline, motivation and optimism may protect against cognitive decline and delay the manifestation of Alzheimer’s. The team is evaluating newly developed instruments for measuring premorbid motivational competence. Established instruments are considered insufficient because they rely mainly on self-report and refer to the present state.

In new research presented at the Alzheimer’s Association Prevention Conference, cognitive functions were assessed in a sample of 120 non-demented individuals aged 60 to 95 years. Motivational and cognitive abilities were estimated using these new instruments and procedures based on the individual’s occupational history. The researchers found that present cognitive abilities (e.g., verbal fluency and working memory) could be independently predicted by former motivational and cognitive abilities.

An ongoing longitudinal study is investigating the predictive power of motivational reserve on the incidence of MCI and dementia.

“Previous research showed that motivational abilities such as self-motivation, goal setting, and emotion regulation can be trained in individuals with and without psychiatric disorders,” Forstmeier said. “The next step is to apply these interventions in people at risk for Alzheimer’s or in the early stages of the disease in order to test their ability to delay onset or progression.”

About the Alzheimer’s Association Prevention Conference

The Alzheimer’s Association International Conference on Prevention of Dementia is the world's only multidisciplinary forum to convene professionals from the fields of bench research, drug discovery, medicine, care and public policy. More than 1,000 dementia experts from around the world will gather to present and discuss the latest detection, treatment and prevention research, and address how together we can prevent Alzheimer's from becoming a global health crisis. The 2007 Alzheimer’s Association Prevention Conference will be held June 9-12 at the Marriott Wardman Park Hotel in Washington, D.C.

About the Alzheimer’s Association

The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, provide and enhance care and support for all affected, and reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. For more information, visit www.alz.org.

• Yan Deschaintre – Vascular Risk Factors Treatment May Slow Dementia Progression. (Funders: Fondation du Centre Hospitalier de l'Université de Montréal, Centre de prévention des maladies neurovasculaires du Centre Hospitalier de l'Université de Montréal, Centre Hospitalier Régional Universitaire de Lille)
• Rosebud O. Roberts – Carotid Endarterectomy and Stroke or TIA are Associated with an Increased Risk of Mild Cognitive Impairment. (Funders: National Institutes of Health, Robert H. Smith and Abigail VanBuren Alzheimer’s Disease Research Program)
• James A. Mortimer – Lower Baseline Weight and Faster Weight Loss Predict Time To Dement in the Nun Study. (Funders: National Institute on Aging)
• Simon Forstmeier – Motivational Reserve: A New Concept Complementing Cognitive Reserve. (Funder: University of Zurich)

Contact:
Alzheimer's Association media line: 312.335.4078 or media@alz.org
Prevention Conference press room, June 9-12: 202.745.2108