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ALZHEIMER'S DISEASE and DEMENTIA

Abstract:  Alzheimer's disease and other dementia strikes up to a quarter of today's older  adults as an unexpected  shock and tragedy.   Yet sadly, this disease can be largely due to the same lifestyle habits that produce premature heart disease and cancer.  Risk nearly doubles for a man or women overweight at a 34 BMI (221 lbs at 5'8" man; 195 lbs 5'4" woman).  Further, the risk of dementia risk for a diabetic is increased 1.7 times, and overweight is a major cause of diabetes.  Risk of a cigarette smoker is nearly doubled, and maintaining a reasonably healthy cardiofitness will reduce risk by 40% vs that usual.  Taking adequate antioxidant vitamins over a span of many years can reduce risk of dementia in half, and taking adequate folic acid can reduce risk another 25%.  This benefit alone should be sufficient to motivate everyone to take these vitamins in amounts suggested in Life Ahead.  A single drink of alcohol each day may reduce risk by up to 40%, and aspirin or other NSAID's can reduce risk another 15%.  In total, good lifestyle habits can reduce dementia risk by at least 10 times vs. those with average habits and 50 times lower than those with very poor life style habits or other risks.  As for most diseases, family history can increase risk 2.5 times, and anyone with a family history of this disease has  a particular need to adopt habits that reduce its risks starting before middle age.  Some lifestyle options are suggested that may slow the progress of dementia for those suffering it.

Background:  Dementia, most of which usually is Alzheimer's disease is the eighth largest cause of death in the US.  But although only about 5% of those of age 65 are afflicted, the risk nearly doubles for each following five years.  A shocking 25% of all of those still alive at age 85 are afflicted today by this seriously life-limiting disease. Today's middle aged health-interested person should easily reach ages 80 to 85 via use of good health habits. But such a longer life will not produce substantially more Well-Days if it is accompanied by this distressing and usually irreversible disease.  Further, nearly everyone that suffers dementia diminishes the life of one or more family care-givers who become obligated to care for the victim.

The hopeful message Life Ahead brings about Dementia is:  Most people probably CAN Prevent it.  The distressing thing is:  Few people today seem to have the slightest idea about when and what they need to do about it.

The two principle forms of dementia are Alzheimer's Disease and Vascular Dementia. Alzheimer's involves a slow deterioration of the brain via the accumulation of plaques, a process that is still poorly understood. Its duration to death is usually about 10 years but can vary from as low as 3 years to a high as 20 years. Vascular dementia that involves about a fourth of all cases usually occurs due to deprivation of oxygen from brain cells due to small strokes or infarcts.  This form is strongly related to risk and occurrence of strokes, and can be produced by high blood pressure and other factors that produce strokes. The exact diagnosis of a form of dementia can be difficult and sometimes can only be done at autopsy.  

It thus becomes obvious that any health-interested person that expects to survive into older age will have a major incentive to avoid suffering dementia.  Fortunately, the risk of this unwelcome disease can be greatly reduced by appropriate life-style habits.  Most of these good habits are the same ones that reduce risk of the other major diseases.  But the additional health gain from these habits in preventing dementia provides a strong further incentive to maintain these healthful habits steadily as age progresses. Dementia strikes without warning today to most that suffer.  Yet its risk probably can be reduced 5 to 10 times by proper lifestyle habits.  Some results from the extensive study of all key research published and that is included in Life Ahead Version #3 follow:

At average US habits risk of dementia advances from 7% at about age 75 to nearly 20% by age 80 and advances much higher than this at still higher ages. With two added high risk factors from such as overweight, smoking, family history or diabetes this risk moves up to 24% and 42%.  Risks of men and women at same habits and age are similar, but because women usually live longer they can have much higher ultimate risks of suffering dementia than men.  The dementia of an older person nearly always also diminishes the quality of life of a much younger family caregiver that becomes involved in caring for the one having this disease. Maintenance of good habits from middle age onward that are described following may reduce risks remarkably to the order of only 1-2% at these same ages. 

Once dementia strikes today it is near impossible to cure. Usually a best that can be done now is to slow its progress somewhat.  Thus a major incentive must be to prevent the disease from occurring in the first place.  The key research results located about reducing risk of dementia is included at the end of this paper. A discussion of the habits can reduce risk of this disease follows. No other single source that both displays the actual available research information and identifies the risks of suffering dementia as accurately is believed to exist.

Dementia and Cigarette Smoking:  Nine studies were located relating the risk of dementia or alzheimers disease to smoking. Only one of the nine failed to find a quite significant effect, with risks for smoking about one pack (20 cigarettes) per day for 35 years for all others varying from 1.73 to 2.72 times. The average risk from these studies was 2.01 times for this amount of smoking.  For some conservatism, Life Ahead uses a factor of 1.8 times for this that is somewhat lower than the risk of smoking on coronary disease.  Because the effect of cigarette smoking on most diseases is so well established the actual research results on this are not included in the appended table of research results.

Dementia, Body Weight, and the BMI:  Studies A1, A2 and A3 are the principal research located relating risk of body weight to the occurrence of dementia. Most results confirm a minimum risk around 21 BMI, with increasing risk as BMI increases to past 30. The low risk corresponds to the quite low weights of 125 and 140 for women and men of 64 and 68 inches height respectively.   The highest level measured in this research was a range cited as 30+ BMI, that probably represented an average value of about 34.  From the low levels of 21-22 BMI to this 34 BMI risk of dementia approximately doubles.  Most results suggest increased risk at levels below 21.  But this may be either in part or all due to a loss in weight by those seriously afflicted, and that could be suffering health problems other than dementia per se.  Study A2 did not confirm this higher risk at the low BMI value. An equation derived from this available data used in Life Ahead is appended to the table of research results.  Risk probably will move higher at still higher values of the BMI, but Life Ahead now identifies only risks confirmed by actual research

Dementia, Exercise, and Cardiofitness:  Eight useful studies relating risk of various forms of dementia to exercise of the type that produces cardiofitness produce quite consistent, similar and convincing results for 15 different comparisons of groups exercising differently.  Risk benefit for exercise was similar for alzheimer's disease and for all forms of dementia. No study provided a clearly quantified level of exercise, and only one (that identified cognitive decline, not risk)  identified cardiofitness specifically. But the extent and level of usual exercise was probably quite modest.   But study B3 showed that the men capable of walking at higher speeds had lower risks, and this confirms again as in all other studies that cardiofitness was the probable factor that produced benefit.

All of the studies of exercise were for older men and women, with most including only those of age 65 or older. The kinds of modest exercise involved in each these studies for this age group probably would produce maxiumum differences in cardiofitness of 10 CFR or less, and group differences of perhaps 5 CFR  The average reduction in risk for the nine different groups compared was a risk of 0.60 for those exercising the most. vs. 1.0 for those exercising least.  Taking a probable maximum difference of 10 in CFR for the risk of 0.60 suggests risk of dementia proceeds at about 0.95 or a 5% reduction for each improvement of 1 in CFR. Life Ahead thus assigns a risk of unity for CFR vs. age values of the average US population, and a benefit of 5% in risk for each increase in CFR above this level to a maximum of 10 CFR only.  It is likely that higher values of the CFR would produce still lower risks of dementia. And seriously exercising older adults can reach values more than twice as high as this via good fitness programs. But Life Ahead now assigns only risk levels verified via multiple research results and for dementia this risk for exercise is a minimum of about 0.60.  Very poor cardiofitness from limited physical activity probably can result in a high risk of suffering dementia that now is not fully reflected in Life Ahead due to lack of data. 

Dementia and Alcohol Intake:  Three studies E1-E3 in the appended table show that 1 to 3 alcoholic drinks per day reduce risk of dementia by 42 to 45%.  No difference was found for the type of alcohol consumed in study E1.  This risk is near identical to that measured for the risk of coronary heart disease and alcohol, and for the risk of diabetes and alcohol. Because the research on coronary heart disease and alcohol was far more extensive, the risk for dementia and this factor is set as same as that for coronary disease.  No mechanisms for the quite significant effect of alcohol on such different disease factors is known.  Although research on dementia endorses "up to 3 drinks per day" the research on alcohol, this research has error margins far too high to identify a best level of alcohol consumption.   The research on heart disease combined with that for alcohol and cancer suggests one drink per day to be best, with consumption above 2 drinks per day to be avoided for best overall health risk.  Health-interested individuals will be seeking a best alcohol amount to develop maximum benefits from alcohol use on all diseases, and not just on risks of some single disease.  Life Ahead computations develop these multiple risks on all major disease, and today this may be the only method developed for solving this complex problem. Using the results of all research on all included diseases, Life Ahead now points to 5-7 alcohol drinks per week as the probable optimum.

Dementia and Diabetes: Eight different studies noted as F1-F8 in the following table each show that risk of dementia is significantly increased for those that have diabetes.  The average risk ratio from these studies of 1.7 is statistically consistent with values from each study.  This average excludes the additional high risk value in F4 those with a gene APOE epsilon4 allele that identifies a particularly high risk for dementia.  This measurement will not be available to most health-interested persons and thus is not included as a factor in Life Ahead.

This risk for dementia from those with diabetes identifies an exceptional risk for body overweight that has been largely overlooked by most health professionals.  First, risk of dementia as per A1-A3 and above doubles for a BMI of about 34 vs. that of a more healthful 22.  Second, risk of diabetes is enormously dependent on overweight, with risk for a 34 BMI 15 times that for a BMI of only 22. Thus those seriously overweight will have a 15 times higher risk of diabetes that in turn exposes them to another 1.7 times risk for dementia.  This means that the pool of older people suffering dementia will be populated by two separate groups of those overweight:  A first group of those without diabetes and a second group of those with diabetes that have suffered this mostly because of their being overweight. Each of these groups then acquires another added risk of dementia of 1.7 times.  For reference men of 5'-8"and women of 5'4" and 148 and 130 pounds respectively have a BMI of 22; those of 224 and 198 will have a BMI of 34.

Most health analysis and advice about weight has considered either risk of heart disease or risk of premature death. These new analyses suggest that these may not be the most important negatives of being overweight.  Rather, a much higher risk for those overweight can be that of suffering diabetes for up to two or more decades, dementia such as alzheimer's for another decade, or both. These are diseases that can seriously diminish the potential enjoyment of life, and are risks hat those overweight incur in addition to that of a somewhat shortened life. 

Dementia and Family History:  Research studies J1-J3 show the risk of dementia vs family history. Most risks are close to the average of 2.5.  The single higher risk value of 8.0 noted for a family member suffering dementia before age 65 is consistent with what would be expected from the general family risk model.  (See diabetes). But further results are needed for any useful verification that the risk of dementia vs. family history follows this general model format. Thus Life Ahead assigns the family risk value of 2.5 times to dementia for a suffering of the disease by any direct parent or sibling. 

Dementia and Foods:  The only food for which risk of dementia was found usefully measured was that of fish.  Each of four studies H1-H4 following provided risk ratios of dementia for different user portions of fish eaten regularly. Information here is only semi-quantitative, but suggests an average risk of 0.50 for amounts of fish identified as "1 or more times per week". This is an impressive reduction in risk from very consistent multiple research results.  Assuming conservatively that the actual amounts of higher fish consumption may have been about 2 portions of average fish per week, and that this included mostly whitefish with some salmon, an average high level of about 720 mg of DHA+EPA, per week would have been involved, with amounts close to zero for most infrequent fish consumers. Assuming 210 avg US consumption per week of DHA+EPA, the formula derived for use in Life Ahead is appended to the table of research results.

Dementia and Antioxidant Vitamins:  Many studies have been published on the relations between risk of dementia and vitamins C, E, and B complex.  Results of the most useful nine studies that include a total of 30 different risk ratios are provided as D1-9 in the appended table. These research results include vitamins in both dietary foods and in supplements, but most results are for use of  supplements. The benefits for reducing risk of dementia and alzheimer's for the various antioxidant vitamins are confirmed by nearly all research comparisons and in aggregate the reduction in dementia risk from use of vitamins is highly significant.  The average risk benefit for vitamins E, C, and B-complex studied in this research are 0.65, 0.69, and 0.85 respectively.  These values are similar to their benefits found for cardiovascular disease and cancer, and in the same order of individual factor benefit.  The amounts of vitamin use associated with these benefits are not defined accurately;  "Any usage" is defined for some study comparisons. 

Three research comparisons of combination usage of Vitamin E and C found a large average benefit factor of 0.34.  The study authors speculated that perhaps their was a synergistic effect of this combination.  But a more likely reason is simply that the combination of the two agents simply provided their expected additive or multipliable benefit 

This pattern of benefits mirrors closely those of the antioxidant model developed for cardiovascular diseases and cancer.  This model assigns benefits for the amounts of four antioxidants, Vitamins Beta-carotene or A, C, E, and selenium present times certain factors. A maximum amount accepted prevents combinations of high amounts of any single or combination of these agents from producing benefits beyond those demonstrated from actual research. Thus the model for cardiovascular diseases is also used to estimate risks of dementia.  The benefits for these vitamins  found in Studies D1-9 developed from smaller amounts of vitamins than those now used in the research and cardiovascular diseases and cancer and are now included in the antioxidant model.  Thus use of this model should provide conservative estimates of antioxidant benefits for dementia.  Life Ahead now acknowledges a risk benefit of up to 0.5 for use of multiple recommended amounts of antioxidants in reducing risk of dementia.

Dementia and Homocysteine, Folic Acid, Vitamin B12:  Many studies relating dementia and alzheimer's disease to homocysteine, folic acid, and B vitamins have been published.   The fact that dementia is increased when homocysteine in the blood is high is extensively confirmed.. The link directly relating levels of folic acid and vitamin B12 to risks of dementia is less certain.  Studies D10 through D13 in the table following are the larger and more quantitative studies located on this. These studies and most others on this relate risks of dementia to blood levels - and not dietary intake per se.  The risk values in these tables are mostly inverted vs. those in the published papers to be consistent with the usual Life Ahead method of showing reduced risks for beneficial factors, and not higher risks for potentially harmful factors. 

All of these studies confirm that low levels of homocysteine and higher levels of folates were beneficial.  Note that these studies involved use for time periods of at least several years.  Some clinical studies that found no effect used very large amounts of folate for only a few weeks. There is no assurance that a short term use of this nutrients would provide much benefit. Despite the mixed results of much research on this, health-interested persons probably will achieve reduced risks of dementia by adhering to the recommended intake of folic acid established elsewhere herein for heart disease. Life Ahead includes an estimated reduction in risk for use of about 800 mg/day vs. low amounts of folic acid of up to 25%.

About the Use of Vitamins:  Arguments about the value of vitamins have been raging for decades. Yet even if all of the massive research on vitamin benefits for the other major diseases including cardiovascular disease and cancer is disregarded, the benefits for

using these agents to reduce risk of dementia alone is more than sufficient to encourage for any health-interested person to take them for a lifetime. It has been estimated that a quarter of all people that reach age 85 today will experience dementia, mostly with alzheimer's disease. Today's health-interested people should have a very high likelihood of moving beyond this age. Thus they have a particular interest in not spending those later years with a sick mind.

Aspirin and NSAID's:  A number of mostly small studies have researched the effect of aspirin and other NSAIDS's as ibuprofen on the risk of dementia.  Two quite useful Meta Analysis studies, G1 and G2 in the following table that identified an average risk incidence of 0.72 (0.56-0.94) and 0.79 (0.68-0.92) and one noted an average prevalence for NSAID users of 0.51.  G1 shows that results were importantly time related, with best results for those taking NSAID's for more than a two years. Results from the few individual studies viewed were mixed, and no effect of dose or amount of aspirin use could be identified.  One study stated that low dose aspirin did not appear effective, another found same results for low dose as for regular dose with each of of limited significance.  Life Ahead acknowledges a conservative benefit of aspirin or other NSAID's on the risk of suffering dementia at risk factor of 0.85, with no effect of dose but for a minimum use of 4 times per week. Most health-interested people will be taking aspirin for its benefit on other major diseases.

Dementia and Mind Developing Activities:  There are a number of studies showing that people that use their brains more obtain lower risks of Dementia.  Like exercise, "If you don't use it, you can lose it."   Some striking results from Study L1 showed that more of each of 4 of 5 'mind using' activities produce much reduced risks of the disease.

Some Research on Those Suffering Dementia:  Life Ahead usually does not attempt to prescribe treatments for those suffering disease, as this is the role of the doctor.  But results from two interesting studies of the effect of lifestyle habits on those with dementia are cited as L1 and L2 following.  L1 provides overall results from an analysis of 30 different studies of physical fitness programs on patients having dementia. Patients improved in three measures of cognitive ability by 41-46%. The extent of real fitness improvement probably was not large for individuals of this age and condition, but even this proved quite beneficial.   Study L2 found that with use of a high daily amount of 2000 IU of Vitamin E, patients gained about 50% more time to a given decline in cognitive ability.  These two studies suggest that with a combination of good regular exercise and Vitamin E could lead to a decline rate of only 1/2 of that usual. Although this disease cannot now be cured, other medical options also are now available that can slow the progress of dementia after it is diagnosed.