Risk factors for Alzheimer's Disease: Brief summaries of research reports

Risk factors

Cholesterol / Fat / Calories

Larger belly in mid-life increases risk of dementia

High blood pressure or irregular heartbeat linked to Alzheimer's disease progression

Alzheimer’s most often found in combination with other disease

More on why high cholesterol might increase your risk of Alzheimer’s

Predicting dementia risk

How mental and physical stimulation slows Alzheimer's

Loss of body mass linked to development of Alzheimer's disease

Alzheimer's, cardiovascular disease share risk factors

Why diet, hormones, exercise might delay Alzheimer’s

Low blood pressure risk factor for Alzheimer's

High cholesterol risk factor for the development of Alzheimer-related amyloid deposits

Cholesterol not a risk factor for Alzheimer's

New study counters previous research linking intake of dietary fat with increased risk of dementia

High calorie consumption associated with higher risk of Alzheimer’s in those genetically disposed to Alzheimer’s

Cholesterol bad for brain too

High blood pressure and cholesterol are risk factors for Alzheimer's disease

March 2008

Larger belly in mid-life increases risk of dementia

A study involving 6,583 people measured abdominal fat at age 40 to 45, and dementia occurrence some 36 years later. Those with the highest amount of abdominal fat were found to be nearly three times more likely to develop dementia than those with the lowest amount of abdominal fat. Having a large abdomen increased the risk of dementia regardless of overall weight and existing health conditions, although being obese as well did increase the risk. Those more likely to have abdominal obesity, were women, non-whites, smokers, people with high blood pressure, high cholesterol or diabetes, and those with less than a high school level of education.  
The study was published online March 26 in Neurology. Full reference
http://www.eurekalert.org/pub_releases/2008-03/aaon-lbi031808.php

November 2007

High blood pressure or irregular heartbeat linked to Alzheimer's disease progression

A study of 135 men and women newly diagnosed with Alzheimer’s found that those with high blood pressure at the time of diagnosis showed a rate of memory loss roughly 100% faster than those with normal blood pressure, and those with atrial fibrillation (an irregular heartbeat) showed a rate of memory decline that was 75% faster than those with normal heartbeats. The findings suggest that treating these conditions may also slow memory loss in Alzheimer’s sufferers.
The results were published in the November 6 issue of Neurology.  Full reference
http://www.eurekalert.org/pub_releases/2007-11/jhmi-hbp103007.php
http://www.eurekalert.org/pub_releases/2007-11/aaon-hbp103007.php

June 2007

Alzheimer’s most often found in combination with other disease

Post-mortem data from a large, long-running study has found that only 30% of people with signs of dementia had Alzheimer’s disease alone. 42% had Alzheimer’s disease with cerebral infarcts (strokes) and 16% had Alzheimer’s disease with Parkinson’s disease (including two people with all three conditions). Infarcts alone caused another 12% of the cases. Vascular dementia caused another 12%. In those without dementia, brain autopsy revealed the presence of Alzheimer’s in 24% of cases, and infarctions in 18%. The finding that Alzheimer’s pathology with cerebral infarcts is a very common combination in people with dementia adds to emerging evidence that dementia risk might be reduced with the same tools we use for cardiovascular disease such as control of blood cholesterol levels and hypertension.
The findings appeared online ahead of print June 13 in Neurology. Full reference
http://www.eurekalert.org/pub_releases/2007-06/nioa-sfm061207.htm

February 2007

More on why high cholesterol might increase your risk of Alzheimer’s

A cell study provides more understanding of why there might be a link between cholesterol and Alzheimer's disease. The study found that proteins which help control cholesterol levels in arterial walls were also present in neurons, and when the genes for these proteins were over-expressed, production of amyloid beta protein fell. The finding suggests a new approach to slowing Alzheimer’s. The study also showed that the apoE protein is extremely good at regulating cholesterol removal from neurons — the gene for this protein is a well-known genetic risk factor for Alzheimer's.
The study appeared in the February issue of the Journal of Biological Chemistry.
http://www.newscientist.com/article/mg19325905.200?DCMP=NLC-nletter&nsref=mg19325905.200

July 2006

Predicting dementia risk

A large Scandinavian study has succeeded in calculating middle-aged people's chances of developing dementia later in life with 70% accuracy. The study confirms the importance of lifestyle factors. The study assessed factors such as blood pressure, body fat and cholesterol levels in 1,400 middle-aged Finns in the 1970s and 1980s, and found that those who at 40 were obese, or had high blood pressure, or high cholesterol levels, were twice as more likely to develop dementia by the age of 60. Having all three of these risk factors increased their chances six-fold. Other risk factors were age and low education.
The study was published online ahead of print on 3 August in Lancet Neurology. Full reference
http://society.guardian.co.uk/health/story/0,,1836464,00.html

September 2005

Loss of body mass linked to development of Alzheimer's disease

People with Alzheimer's disease are known to lose weight and body mass after they have the disease, but now the Religious Orders Study has revealed that loss in body mass index is associated with a greater risk of developing the disease. People who lost approximately one unit of BMI per year had a 35% greater risk than people with no change in BMI; those with no change in BMI had a 20% greater risk of developing the disease than that of people who gained six-tenths of a unit of BMI per year. A similar relationship was also found between changes in BMI and rate of cognitive decline. The findings are supported by recently published findings of the Honolulu-Asia Aging Study, showing that dementia-associated weight loss in Japanese-American men begins before the onset of dementia and accelerates by the time of diagnosis.
The research was reported in the September 27 issue of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2005-09/nioa-lob092105.htm

July 2004

Alzheimer's, cardiovascular disease share risk factors

A study of 4,081 women aged 65 years and older has investigated the relationship between cardiovascular risk factors and cognitive function. The researchers found a consistent increase in cognitive health paralleling higher levels of HDL (“good” cholesterol). A less robust correlation was seen for lower levels of LDL (or "bad") cholesterol and better cognitive performance. Triglyceride levels did not appear to influence cognition.

A study of over 700 elderly men and women has investigated the relationship between diabetes and cardiovascular disease risk factors and cognitive health. Researchers found that the presence of coronary heart disease, high cholesterol, or hypertension increased the risk of later cognitive decline, with a particularly strong effect in African Americans. They also found that although the diagnosis of diabetes increased the risk of cognitive decline by as much as two fold, the presence of high levels of fasting glucose (therefore, low insulin levels) substantially decreased the risk of cognitive decline in diabetic patients.

Data from a 24-week pilot trial of the diabetes drug rosiglitazone in patients with mild cognitive impairment (MCI) or very mild Alzheimer's disease found those who received rosiglitazone – a drug that boosts insulin activity – did not decline in their performance on memory and attention tests.

Data from an ongoing study of memory and aging among more than 3,300 residents age 65 and over from Cache County, Utah, has found that those who had used anti-hypertension medications had a lower risk of getting Alzheimer's. This benefit seemed most closely related to the use of diuretics. Among this group of drugs, "potassium-sparing" diuretics were associated with the greatest reduction in Alzheimer risk. The use of other hypertension drugs, such as ACE (angiotensin converting enzyme) inhibitors, calcium channel blockers, and beta-blockers, did not affect Alzheimer risk.
References
http://www.eurekalert.org/pub_releases/2004-07/aa-acd070804.htm

February 2004

Why diet, hormones, exercise might delay Alzheimer’s

A theory that changes in fat metabolism in the membranes of nerve cells play a role in Alzheimer's has been supported in a recent study. The study found significantly higher levels of ceramide and cholesterol in the middle frontal gyrus of Alzheimer's patients. The researchers suggest that alterations in fats (especially cholesterol and ceramide) may contribute to a "neurodegenerative cascade" that destroys neurons in Alzheimer's, and that the accumulation of ceramide and cholesterol is triggered by the oxidative stress brought on by the presence of the toxic beta amyloid peptide. The study also suggests a reason for why antioxidants such as vitamin E might delay the onset of Alzheimer's: treatment with Vitamin E reduced the levels of ceramide and cholesterol, resulting in "a significant decrease in the number of neurons killed by the beta amyloid and oxidative stress.
The study was published in the February 17 issue of Proceedings of the National Academy of Sciences. Full reference
http://www.eurekalert.org/pub_releases/2004-02/aaft-nsm021004.htm

December 2003

Low blood pressure risk factor for Alzheimer's

A long-term study of 488 adults over 75 (the Bronx Aging Study) found that 122 participants developed dementia (65 Alzheimer’s, 28 vascular dementia, 29 other), and that the relative risk of dementia increased as a function of decreases in blood pressure (diastolic and mean arterial). Low diastolic BP significantly increased the risk of developing Alzheimer’s, but not vascular dementia. Those with mildly to moderately raised systolic BP had a reduced risk of developing Alzheimer’s. The risk of developing dementia was higher in those who had persistently low BP over 2 years.
The report appeared in the December 23 issue of Neurology. Full reference

July 2003

High cholesterol risk factor for the development of Alzheimer-related amyloid deposits

A review of autopsy cases of patients over 40 years old found that high blood cholesterol levels were correlated with the presence of amyloid deposits in the brain in the youngest subjects (aged 40-55).
The report appeared in the July 22 issue of Neurology. Full reference

May 2003

Cholesterol not a risk factor for Alzheimer's

Previously, the long-running, large-scale Framingham study found people with elevated levels of homocysteine in the blood had nearly double the risk of developing Alzheimer’s disease (AD). The study now clarifies the inconclusive results from previous studies regarding whether plasma cholesterol levels are associated with increased risk of Alzheimer disease (AD). They found that, after adjustment for age, sex, APOE genotype, smoking, body mass index, coronary heart disease, and diabetes, there was no significant association between AD risk and cholesterol level.
The study was reported in the May 12 issue of the Archives of Internal Medicine. Full reference
http://archinte.ama-assn.org/cgi/content/abstract/163/9/1053

December 2002

New study counters previous research linking intake of dietary fat with increased risk of dementia

Previous studies suggesting that fat may be involved in the development of dementia and Alzheimer’s disease have been contradicted by a new study involving over 5,000 elderly people over a period of six years. The study found no correlation between fat and cholesterol intake and risk of dementia, and no evidence for a reduction in risk for those taking cholesterol lowering medication.
The study was reported in the December 24 issue of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2002-12/aaon-nsc121602.htm

August 2002

High calorie consumption associated with higher risk of Alzheimer’s in those genetically disposed to Alzheimer’s

980 elderly individuals without Alzheimer’s participated in a four-year study to investigate whether there was any link between caloric intake and Alzheimer’s. During the course of the study, 242 patients developed Alzheimer’s, and 28% tested positive for the APOE epsilon 4 gene. Participants were divided into four groups depending on how many calories they consumed daily. 263 of the participants tested positive for the APOE epsilon 4 gene, and among them, those who consumed the most calories had a 2.3 times greater chance of developing Alzheimer’s compared to those who ate the fewest calories. For those without the ApoE e gene, calorie and fat intake were not associated with a greater risk of Alzheimer’s.
The study was reported in the August issue of the Archives of Neurology.
http://www.eurekalert.org/pub_releases/2002-08/jota-cmc081202.htm

March 2002

Cholesterol bad for brain too

An analysis of data on 1037 older women who had participated in a clinical trial of hormone replacement therapy found that high cholesterol levels increase the risk of cognitive impairment. It is speculated that, in addition to clogging arteries, and possibly leading to vascular changes in the brain, cholesterol may promote the clumping of a protein called beta-amyloid, which is believed to damage the brain in Alzheimer’s disease patients.
The study was published in the March issue of Archives of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2002-03/uoc--cbf031302.htm

July 2001

High blood pressure and cholesterol are risk factors for Alzheimer's disease

A large-scale Finnish study following 1449 men and women over 21 years found that raised systolic blood pressure and high serum cholesterol concentration, particularly in combination, in midlife, increase the risk of Alzheimer's disease in later life. Raised diastolic blood pressure had no significant effect.
The study was reported in the British Medical Journal.
http://www.bmj.com/cgi/content/full/322/7300/1447

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Homocysteine / B12 / Folate

Folates more effective in limiting Alzheimer's disease risk than antioxidants, other nutrients

Moderately high homocysteine linked to Alzheimer’s risk

Folic acid possibly a key factor in preventing Alzheimer's disease

High homocysteine levels may double Alzheimer's ris

Research ties vitamin B12 and folate deficiencies with Alzheimer's disease

High homocysteine levels are associated with decreased memory capability after age 60

August 2005

Folates more effective in limiting Alzheimer's disease risk than antioxidants, other nutrients

Analysis of data from the Baltimore Longitudinal Study of Aging has revealed that those with higher intake of folates, vitamin E and vitamin B6 had a lower risk of developing Alzheimer’s. When the three vitamins were analyzed together, only folates were associated with a significantly decreased risk. Those who had at least 400mcg of folates a day (the recommended daily allowance) had a 55% reduction in risk of developing Alzheimer’s. Unfortunately, most people who reached that level did so by taking supplements, suggesting the difficulty of doing so through diet alone. Folates are abundant in foods such as liver, kidneys, yeast, fruits (like bananas and oranges), leafy vegetables, whole-wheat bread, lima beans, eggs and milk; however, they are often destroyed by cooking or processing. No association was found between vitamin C, carotenoids (such as beta-carotene) or vitamin B-12 intake and decreased Alzheimer's risk.
Results appear in the inaugural issue of Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Full reference
http://www.eurekalert.org/pub_releases/2005-08/uoc--fme081105.htm

October 2002

Moderately high homocysteine linked to Alzheimer’s risk

A study of 83 Alzheimer’s patients, 78 patients with vascular dementia, 64 stroke patients, and 71 healthy controls, found that elevated levels of homocysteine were associated with a more than five-fold increase in the risk for stroke, a nearly five-fold risk for vascualr dementia, and almost triple the risk for Alzheimer's disease. High blood levels of homocysteine have been found to be associated with an increased heart attack risk in several studies. High levels of homocysteine have been found to be associated with deficiencies in vitamin B12 and folate, and also with smoking.
The report appeared in the October issue of Stroke.Full reference
http://www.eurekalert.org/pub_releases/2002-10/aha-mhh092602.htm

March 2002

Folic acid possibly a key factor in preventing Alzheimer's disease

Experiments with mice bred with mutant genes that cause Alzheimer's disease found that those mice fed on a diet deficient in folate had fewer neurons in the hippocampus ( a brain region critical for learning and memory that is destroyed as plaques accumulate during Alzheimer’s disease), and elevated levels of homocysteine. Researchers suspect that increased levels of homocysteine in the brain caused damage to the DNA of nerve cells in the hippocampus. In the mice fed an adequate amount of folate, nerve cells in this brain region were able to repair the damage. But in those mice fed a folate-deficient diet, nerve cells were unable to repair this damage. A human study is being planned.
Green leafy vegetables, citrus fruits and juices, whole wheat bread and dry beans are good sources of folate. In the U.S., since 1998, the Food and Drug Administration has required the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products.
The study was published in the March 1 issue of the Journal of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2002-03/nioa-fap030102.htm

February 2002

High homocysteine levels may double Alzheimer's risk

Findings from the long-running Framingham study found people with elevated levels of homocysteine in the blood had nearly double the risk of developing Alzheimer’s disease (AD). This study is the first to tie homocysteine levels measured several years before with later diagnosis of AD and other dementias, and provides the most powerful evidence yet of the link between high homocysteine levels and AD.
The report appeared in the February 14, 2002, issue of The New England Journal of Medicine. Full reference
http://www.eurekalert.org/pub_releases/2002-02/nioa-hhl021202.htm

May 2001

Research ties vitamin B12 and folate deficiencies with Alzheimer's disease

People with low levels of B12 or folate may have a higher risk of developing Alzheimer's disease. A 3-year Swedish study of 370 people 75-years-old and older found that more than half (46 out of 78) of those diagnosed with dementia during the timeframe of the study had both low levels of vitamin B12 or folate and Alzheimer's type dementia. Low vitamin B12 and folate levels have long been observed in elderly people, and it has been theorized that this vitamin deficiency might be tied to neurological or psychiatric disorders. This study breaks new ground by connecting these deficiencies with Alzheimer's disease.
Vitamins B12 and folate (a form of water-soluble vitamin B) are found in common foods. Vitamin B12 is naturally found in animal foods including fish, milk and milk products, eggs, meat, and poultry. Leafy greens such as spinach and turnip greens, dry beans and peas, fortified cereals and grain products, and some fruits and vegetables are rich food sources of folate.
The study was reported in the May 8 issue of Neurology.
http://www.eurekalert.org/pub_releases/2001-05/AAoN-RtvB-0705101.htm

High homocysteine levels are associated with decreased memory capability after age 60

Recent studies have linked Alzheimer disease and dementia after multiple strokes to extremely high serum homocysteine concentrations. A survey of 1299 men and women aged 60 and over, none of who had previously had a stroke, found an independent relationship between very high homocysteine levels and poor performance on cognitive tests. The folate status of the participants was checked as folate has been shown to significantly modify homocysteine levels. Story recall was worse among subjects with a combination of low folate and high homocysteine than in those whose homocysteine levels were normal or low. Homocysteine levels increased with age and were accompanied by a comparable decline in folate status. The researchers found independent associations between the highest levels of homocysteine and poorer recall. Among subjects with the highest level of homocysteine, the odds of passing a word delayed-recall test were identical whether their folate status was high or low.
This study appeared in the American Journal of Clinical Nutrition.
http://www.eurekalert.org/pub_releases/2001-04/AJoC-Hhla-2504101.htm

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Insulin

Support for view of Alzheimer's as form of diabetes

Diabetes associated with increased risk of mild cognitive impairment

High blood sugar linked to MCI and dementia

Reduced insulin in the brain triggers Alzheimer's degeneration

Link between insulin and Alzheimer's

Diabetics at significantly higher risk for Alzheimer's disease

Insulin-degrading enzyme may affect risk of Alzheimer’s disease

September 2007

Support for view of Alzheimer's as form of diabetes

Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a third form of diabetes. A new study clarifies the connection between insulin and Alzheimer’s. It seems that the toxic protein ADDL, found in the brains of individuals with Alzheimer’s, removes insulin receptors from nerve cells, rendering those neurons insulin resistant. The findings suggest that some existing drugs now used to treat diabetic patients may be useful for Alzheimer’s treatment.
The findings were published online August 24 in FASEB Journal.   Full reference
http://www.eurekalert.org/pub_releases/2007-09/nu-dst092607.php

April 2007

Diabetes associated with increased risk of mild cognitive impairment

A study involving 918 individuals older than 65 years (average age 75.9) who did not have mild cognitive disorder or dementia when they enrolled has found that, over some 6 years, diabetes was related to a significantly higher risk of developing amnestic mild cognitive impairment, after controlling for other risk factors. The results support other findings that type 2 diabetes mellitus increases the risk of Alzheimer's.
The report appeared in the April issue of Archives of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2007-04/jaaj-dmb040507.htm

August 2006

High blood sugar linked to MCI and dementia

The first study to investigate the association over time between blood sugar and the risk of cognitive difficulties involved 1,983 post-menopausal women (mean age 67 years) and found that each 1% increase in their glycosylated hemoglobin level at the start of the four-year study period was associated with a 40% increased risk of developing MCI or dementia four years later. The glycosylated hemoglobin test gives a more stable measure of blood sugar level than the standard test, which measures blood sugar it the time of testing. A result of 7% or less indicates good long-term blood sugar control. Those with a level of 7% or more were four times more likely to develop MCI or dementia than women who tested at less than 7%.
The report appeared in the Journal of Nutrition, Health, and Aging. Full reference
http://www.eurekalert.org/pub_releases/2006-08/uoc--chb080906.htm

March 2006

Reduced insulin in the brain triggers Alzheimer's degeneration

By depleting insulin and its related proteins in the brain, researchers have replicated the progression of Alzheimer's disease – including plaque deposits, neurofibrillary tangles, impaired cognitive functioning, cell loss and overall brain deterioration – in an experimental animal model. Brain deterioration was not related to the pancreas, raising the possibility that Alzheimer's is a neuroendocrine disorder, or a Type 3 diabetes.
The study was published in the Journal of Alzheimer's Disease. Full reference
http://www.eurekalert.org/pub_releases/2006-03/l-rii031606.htm

March 2005

Link between insulin and Alzheimer's

A new study has found that insulin and its related proteins are produced in the brain as well as the pancreas, and that reduced levels of these contribute to the degeneration of brain cells, an early symptom of Alzheimer's disease. The finding raises the possibility of a Type 3 diabetes.
The findings are reported in the March issue of the Journal of Alzheimer's Disease. Full reference
http://www.eurekalert.org/pub_releases/2005-03/l-rdl030205.htm

May 2004

Diabetics at significantly higher risk for Alzheimer's disease

New findings from the Religious Orders Study add to research suggesting a link between diabetes mellitus and an increased risk of developing Alzheimer's disease. Some aspects of cognitive function appear to be affected differently than others, in particular perceptual speed declined significantly faster in those with diabetes.
The study appeared in the May issue of the Archives of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2004-05/rpsl-das051204.htm

May 2003

Insulin-degrading enzyme may affect risk of Alzheimer’s disease

A new mouse study suggests that low levels of insulysin, an enzyme that degrades insulin, could increase the risk for Alzheimer's, and points to a new mechanism linking diseases like diabetes and Alzheimer's — the competition of multiple substrates, such as insulin and amyloid-beta, for a limiting amount of the insulysin enzyme. The insulysin enzyme, it seems, also degrades amyloid-beta peptides, and even a partial decrease in insulysin activity was found to raise amyloid-beta peptide levels in the brain.
The study was published online before print in Proceedings of the National Academy of Sciences. Full reference
http://www.eurekalert.org/pub_releases/2003-05/uots-iem050603.htm

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