Introduction:
The topics which will be covered here include cognitive decline, mild cognitive impairment, vascular dementia and Alzheimer’s disease (AD) which is also known as Senile Dementia of the Alzheimer’s Type (SDAT). The focus here will be on evidence based-options for enhancement of cognitive function and potential prevention of cognitive impairment and AD. Established impairment of cognitive function may not be reversible especially if progression is occurring or a diagnosis of AD is already established. If established cognitive impairment is present, the only realistic goal may be to attempt to stabilize progression and prevent further decline. Adults with the concern of family history of dementia or any current cognitive impairment may use this data to provide the best chances of accomplishing a lower risk of AD.
Alzheimer’s disease (AD) dementia:
AD is a type of dementia without a clear cause that usually begins with mild cognitive impairment such as memory loss, language difficulty, reduced emotions, poor judgement, and loss of other cognitive skills. It is no longer believed to be linked with aluminum, mercury or lead, but may be connected to genetic and environmental factors.
Vascular dementia:
Vascular dementia may occur with similar symptoms as AD but in a manner of a stepwise decline of cognitive function from a process of ischemic demyelination. Ischemic demyelination occurs as small blood vessels “close off” due to atherosclerosis over time resulting in atrophy and lower cognitive function.
Early onset AD:
Early onset AD is less common than late onset but may occur in patients under 60 years old. This type often runs in families and may be due to a genetic link such as the apolipoprotein E epsilon4 allele. Early onset AD may worsen more rapidly than late onset.
Late onset AD:
Late onset AD in those over 60 years old is more common than early onset and can also run in families. According to Kivipelto M et al, an elevated mid-life total cholesterol level, a high midlife systolic blood pressure, and the apolipoprotein E epsilon 4 allele gene are independent risk factors for late-life Alzheimer disease. (1)
Symptoms of AD, vascular dementia and other dementias:
Early symptoms:
These may include forgetting keys or important items, misplacement of items, word finding difficulty, less expression of emotion, losing social skills, and becoming lost in a previously familiar place.
Later symptoms:
These might be loss of sleep pattern or sundowning (awake at night), losing self identity, loss of language, loss of ability to read or write, depression, agitation, psychosis, and inability to perform activities of daily living.
Risk factors for Alzheimer’s disease (AD):
A literature review by Barranco-Quintana JL et al on the major risk factors for Alzheimer’s disease (AD) listed the 10 major risk factors which included: 1) Age. Considered the principal marker for risk of AD; 2) Sex. Women are at higher risk; 3) Genetics; 4) Tobacco; 5) Lower risk with wine consumption; 6) Family history of dementia. About 40% of persons with AD have family history of dementia; 7) Non-steroidal anti-inflammatories (NSAIDs) (examples are aspirin, ibuprofen, naproxen); 8) Cranio-encephalic trauma. This is controversial; 9) Education. AD has been found to increase in low education persons; 10) Diet. Eating a diet rich in antioxidants or in supplementary forms is beneficial. (14)
Integrative Medicine Interventions:
Nutritional and dietary interventions which may improve cognitive decline:
Low serum vitamin B12 levels (<150 ρmol/L) are associated with neurodegenerative disease and cognitive impairment. This analysis of 17 studies (looking at the relationship between vitamin B12 and cognitive impairment) demonstrated that vitamin B12 supplements administered orally or injected at 1mg daily corrected the deficiency, and moreover, improved cognitive ability, though only among patients with pre-existing vitamin B12 deficiency. Vitamin B12 therapy does was not shown to improve cognitive ability in patients without pre–existing vitamin B12 deficiency. (2)
Elevated homocysteine levels (hyperhomocysteinemia) appears to increase risk for Alzheimer’s disease, vascular dementia, cognitive impairment or stroke. Folic acid, vitamin B6, and vitamin B12 may reduce homocysteine levels. According to Herrmann W et al, human studies suggest that homocysteine (Hcy) plays a role in brain damage, cognitive and memory decline and is a risk factor for neurodegenerative diseases such as Alzheimer’s disease, vascular dementia, cognitive impairment or stroke. Trials evaluating supplementation of B vitamins showed a benefit in slowing atrophy of the brain. A meta-analysis of secondary prevention trials showed that supplementation with folic acid, vitamin B6, and vitamin B12 caused a decrease in plasma Hcy resulting in a trend toward a lower risk of stroke. The analysis of the trials suggested that elevated plasma Hcy is common in elderly people and therefore these patients should be treated with nutritional therapy. It is prudent to identify B vitamin deficient subjects and to ensure sufficient vitamin intake. The author believes that Hcy is a potential biomarker in age-related neurodegenerative diseases and that lowering Hcy may improve clinical outcomes in patients. (21)
Elderly subjects who consumed the most fruits and vegetables exhibited the strongest cognitive performance in a dose dependent relationship up to 500 grams per day. Researchers studied the diets of 2,031 elderly Norwegian men and women (aged 70–74 years; 55% women) to examine the relationship between intake of different plant foods and cognitive performance in elderly individuals in a cross-sectional study. Subjects completed a battery of cognitive tests and completed a validated and comprehensive food frequency questionaire (FFQ) to assess regular food intake. Study participants who consumed the most fruits and vegetables exhibited the strongest cognitive performance, with a marked dose-dependent relationship up to about 500 grams per day. Specific foods associated with this effect included carrots, cruciferous vegetables, citrus fruits, and whole grain breads. The dose-related increase of intakes of grain products and potatoes hit a plateau around 100 g/d to 150 g/d. The only negative association for cognitive health was found in white bread. In conclusion, among the elderly, a diet rich in plant foods is associated with better performance in several cognitive abilities in a dose-dependent manner. (3)
Japanese Americans who drank 3 or more tea, wine, fruit, and vegetable juice servings per week were less likely to develop Alzheimer’s disease. Dementia-free Japanese-Americans (n= 1,836) completed a food frequency questionnaire and underwent clinical evaluation at baseline from 1992 to 1994. They then underwent clinical evaluation for Alzheimer’s every two years through 2001. Compared with those who averaged less than one glass of tea, wine, and fruit and vegetable juice per week, those who drank three or more were 76% less likely to develop Alzheimer’s disease (hazard ratio [HR]=0.24, p<0.01). Even those who drank only one or two serving weekly had had a 6% reduction in risk of Alzheimer’s compared with those who consumed less juice (HR=0.84). In conclusion, this prospective study of older Japanese-Americans suggests that fruit or vegetable juice may help fend off Alzheimer’s disease. (4)
Green leafy and cruciferous vegetable intake was associated with slower rates of cognitive decline. This was found in a study by Kang et al which prospectively looked at the relationship between fruit and vegetable consumption on cognitive function among 13,388 women. This cohort study detected possible memory benefits from diets high in vegetables. Consumption of vegetables—particularly the green leafy variety—was associated with slower rates of cognitive decline. Women in the study who ate the most cruciferous vegetables had a slower cognitive decline compared with those who ate the least cruciferous vegetables. Cruciferous vegetables are the plant family which includes broccoli, cabbage, kale and brussel sprouts. Fruit consumption did not have the same cognitive benefit as vegetable intake. (5)
A higher intake of vegetables appears to be associated with a lower risk of dementia and a slower rate of cognitive decline. Loef M et al completed a systematic review of cohort studies which looked to at the relationship between fruit and vegetable consumption has upon cognitive decline and dementia. Nine studies with a total of 44,004 participants were incorporated in the review, providing they had follow-up of 6 months or more; the use of tests to measure cognitive changes; and reported risk estimates or number of events for Alzheimer’s disease, dementia, mild cognitive impairment or cognitive decline based on measures of fruit and vegetable consumption. The review concluded that a higher intake of vegetables is associated with a lower risk of dementia and a slower rate of cognitive decline. The strongest associations were found for cruciferous vegetables (broccoli, cabbage), lettuce, zucchini and squash, legumes and green leafy vegetables. In order to prevent Alzheimer’s disease and cognitive decline with age, there was moderate support for the recommendation to eat three servings or greater than 200 grams of vegetables per day. The evidence for such an association is not apparent for fruit consumption. (6)
Apple juice may improve behavioral and psychotic symptoms in dementia patients. After 21 institutionalized patients with moderate-to-severe Alzheimer’s disease consumed two 4-oz glasses of apple juice a day for a month, their caregivers reported no change in the patients’ Dementia Rating Scale or their day-to-day abilities. Behavioral and psychotic symptoms (anxiety, agitation, and delusion) associated with their dementia (as quantified by the Neuropsychiatric Inventory), improved by approximately 27%. (7)
Blueberry intake may protect brain neurons. A study by Brewer GJ et al performed with laboratory rats looked at blueberry supplementation and whether it reverses age-related cognitive decline. Researchers found that high antioxidant blueberry extract protected brain neurons from accumulation of amyloid-beta, a type of protein that forms deposits in the brain that are associated with risk of dementia. Amyloid-beta is also associated with increased immune reactivity that can lead to inflammation and nerve cell damage. In this study blueberry treatment showed strong inhibition of these effects in all ages. (8)
As the population ages, dementia is on the rise. Adding antioxidants and anti-inflammatories to the diet, such as blueberries, has been found to improved brain signals, memory function, and the metabolism of glucose. This is predicated upon a study of nine older adults with early memory changes. Individuals in this study were given blueberry juice that was pressed, filtered, and pasteurized. Daily consumption was maintained between 6 mL/kg and 9 mL/kg, using a dosing schedule aligned by body weight. Individuals weighing 54 to 64 kg were prescribed 444 mL/day, those weighing between 65 and 76 kg consumed 532 mL/day, and those weighing between 77 and 91 kg digested 621 mL/day. At 12 weeks, there was improved paired associate learning, word list recall, potential trends in the reduction of symptoms of depression, and lower blood sugar levels. (13)
Fisetin, a flavonol found in plant-based foods such as strawberries, apples, grapes and onions, was found to inhibit amyloid protein formation along with the flavonoids luteolin, quercetin and myricetin. Amyloid beta protein is thought to cause the progressive neuronal loss in Alzheimer’s disease. (9)
Alzhemier’s and fish consumption:
Fish consumption of once per week or more in the form of fresh fish, tuna, fish cakes, fish sticks and fish sandwiches was associated with reduced risk of Alzheimer’s disease. Researchers looked at 815 older adult participants (aged 65-95 years) not affected by Alzheimer’s disease to find out whether eating fish protects against Alzheimer’s disease. After a 2.3 year follow-up period a total of 131 had developed Alzheimer’s. Compared with those who rarely or never eat fish, a 60% reduced risk of Alzheimer’s disease was reported among participants who consumed fish once per week or more. (29)
Aerobic exercise may improves cognitive function and impairment:
Aerobic exercise improved multitasking, cognitive flexibility, information processing efficiency, and selective attention especially in women. Baker and colleagues report the results of a randomized, controlled clinical trial involving 33 adults with mild cognitive impairment (MCI) in 17 women with an average age of 70. A group of 23 were randomly assigned to an aerobic exercise group and exercised at high intensity levels under the supervision of a trainer for 45 to 60 minutes per day, 4 days per week. The control group of 10 individuals performed supervised stretching exercises according to the same schedule but kept their heart rate low. Fitness testing, body fat analysis, blood tests of metabolic markers and cognitive functions were assessed before, during and after six-months. A total of 29 participants completed the study. Overall, the patients in the high-intensity aerobic exercise group experienced improved cognitive function compared with those in the control group. Specifically, positive effects were seen in multitasking, cognitive flexibility, information processing efficiency and selective attention compared with the stretching control group. These effects were more pronounced in women than in men, despite similar increases in fitness. On average, effect on women was more than twice that for men. The sex differences may be related to the metabolic effects of exercise, as changes to the body’s use and production of insulin, glucose and the stress hormone cortisol differed in men and women. Results also indicate deterioration in the cognitive function of women in the control group, suggesting aerobic exercise mitigates the progression of cognitive impairment. This study suggests that rigorous aerobic exercise was an effective, non-pharmaceutical approach to combat the effects of cognitive impairment, particularly for women. (10)
Aerobic exercise may improve Alzheimer’s dementia. Seven cohort studies were compared in an analysis in Germany which discussed the benefits of distance walking, aerobic exercise and various other physical activities in Alzheimer’s disease and cerebrovascular dysfunction. The study stated that vascular regeneration, organ blood flow, induction of antioxidant pathways, and enhanced angiogenesis has been experienced in individuals with exercise training. A large clinical trial was included in the analysis which suggested a significant reduction of Alzheimer’s dementia accompanied by extensive cardiovascular changes experienced with exercise. According to the study, exercise may benefit Alzheimer’s disease by up-regulation of antioxidant enzymes and angiogenesis. Furthermore the study concluded that regular exercise is thought to counteract Alzheimer’s disease by improving endothelial dysfunction (the ability of blood vessels to respond appropriately to the body’s blood flow needs), upholding neuronal plasticity, and build a vascular reserve. (11)
Aerobic exercise resulted in less brain tissue loss: Previous research has demonstrated that the human brain gradually loses tissue density after the age of thirty in the frontal, parietal, and temporal cortices as a function of the aging process. A study looked at MRIs of people 55 years and older showed that there were marked differences in brain tissue densities based upon age and amount of aerobic fitness. The study showed that people involved in cardiovascular fitness greatly maintained more brain volumes and cognitive function in these areas of the brain. (12)
Caffeine intake has been found to have an inverse association and decrease in risk of AD:
A case-control study done by Maia et al., tested to see if caffeine intake protects against Alzheimer’s disease (AD). In a questionnaire about caffeine intake, researchers calculated the estimated intake depending on the amount of caffeine in different caffeinated products. There were also questions involving tobacco and alcohol consumption. This study reported a significant inverse association between caffeine intake and AD. In other words, an increase in caffeine intake decreased the risk of AD. Hypertension, diabetes, stroke, head trauma, smoking habits, alcohol consumption, non-steroid anti-inflammatory drugs, vitamin E, gastric disorders, heart disease, education and family history of dementia were not statistically significantly associated with AD. Patients with AD had an average daily intake of about 73.9 mg of caffeine during the 20 years prior to diagnosis. Meanwhile, the controls had about 198.7 mg of daily caffeine intake during the same 20 years as their matched pair in the study. These findings suggest that consuming caffeine may have a lower risk Alzheimer’s disease. (15)
Studies consistently support coffee’s favorable effects against cognitive decline, dementia, and Alzheimer’s disease (AD). In a review done by Eskelinen et al., it was determined that moderate caffeine intake, coffee in particular, is associated with a decreased risk in the diagnosis of dementia/AD. This review included nine longitudinal studies and the CAIDE study (Cardiovascular risk factors, Aging and Dementia). The results from the longitudinal studies were inconsistent, but most studies (3 out of 5) support coffee’s favorable effects against cognitive decline. The CAIDE study showed that drinking 3 to 5 cups per day at midlife appears to decrease the risk of dementia/AD by about 65 percent later on. These findings suggest that coffee drinking may be associated with a decreased risk of dementia/AD. (16)
Researchers suggest that the beneficial effects of caffeine intake on improving working memory (WM) may be linked to personality. Fifty-nine participants received caffeine (200 mg) or placebo prior to completing a N-Back WM task, similar to a memory which is used to measure working memory. Compared to placebo, caffeine improved working memory performance in extroverts but not in introverts. (30)
Alcohol intake and Alzheimer’s Disease (AD):
Wine consumption was associated with a lower risk of AD. The relationship between alcohol consumption and risk of AD and dementia associated with stroke (DAS) was analyzed in this cohort study of 980 participants aged 65 and older. Dementia was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria and classified as AD or DAS. After 4 years of follow-up, 260 individuals developed dementia (199 AD, 61 DAS). Consumption of up to 3 servings of wine daily was associated with a lower AD risk (Hazard ratio = 0.55). Liquor, beer, and total alcohol were not associated with a lower risk of AD. Analyses of the APOE-epsilon 4 allele, a gene responsible for production of a protein which breaks down componenets of trigycerides, showed that the relationship between wine consumption and lower risk of AD was seen only in individuals without the APOE-epsilon 4 allele. (17)
An overall risk reduction in Alzheimers and other dementia was seen in moderate alcohol drinkers compared to nondrinkers and alcohol abusers. (18)
Natural Supplements with evidence for benefit in Alzheimer’s Disease:
Saffron and Alzheimer’s disease:
Crocus sativus (saffron), commonly used as a spice, was studied in relation to cognitive function in 46 patients with mild to moderate Alzheimer’s disease (AD). This 16-week, randomized and placebo-controlled trial, showed that 15 mg of saffron twice per day was both safe and effective in mild to moderate Alzheimer’s disease. Results show that among patients who took saffron, cognitive function (as measured by AD assessment scale-cognitive subscale [ADAS-cog] and clinical dementia rating scale-sums [CDR] of boxes) was significantly better when compared to those taking similar looking placebo pills. (19)
Saffron extract in the treatment of 54 Persian-speaking patients with mild-to-moderate Alzheimer’s disease (aged 55 years or older) was analyzed in this 22-week, double-blind study. Each participant was randomly assigned to receive saffron at 30 mg/day (15 mg twice per day) or donepezil at 10 mg/day (5 mg twice per day). Cognitive function in both groups was measured using the Alzheimer’s Disease Assessment Scale-cognitive subscale and Clinical Dementia Rating Scale-Sums of Boxes scores compared with baseline. Researchers found saffron had a similar effect to the drug donepezil in the treatment of mild to moderate Alzheimer’s—but with significantly less vomiting experienced among the saffron group. (20)
Omega 3 fatty acids, DHA, and EPA in cognitive impairment and Alzheimer’s disease:
Omega 3 fatty acids contains DHA (docosahexaenoic acid), and EPA (eicosapentaenoic acid). Omega 3 fatty acids may help counteract cognitive decline. A randomized, controlled, cross-over study involving 40 healthy adults, ages 51-72 years old, found that omega-3 fatty acids improved cognitive function and cardiometabolic risk factors after 5 weeks of supplementation. Subjects received either 3g daily fish oil or placebo for 5 weeks, separated by a 5-week washout period. Results showed subjects performed better on working memory tests and had lowered blood pressure and plasma triacylglyceride levels with omega-3 compared to placebo. Systolic blood pressure, f-glucose, and s-TNF-alpha, were inversely related to the performance in cognitive tests. The results from this study suggest that omega-3 fatty acids may improve cognitive performance in healthy subjects after only five weeks and may help prevent or delay onset of metabolic disorders and the associated cognitive decline. (22)
Karin Yurko-Mauro, PhD led the Memory Improvement with DHA (docosahexaenoic acid) Study (MIDAS Study) which randomized 485 subjects 55 years old or older with mild cognitive impairment to receive 900 mg of algae derived DHA or placebo for 24 weeks. Before and after taking the DHA, the CANTAB Paired Associate Learning test (PAL), was used to evaluate visual-spatial learning and memory recall ability of the subjects. Positive effects of the treatment group included an average reduction in 4.5 errors from a baseline of 13.4 compared to a reduction of 2.5 errors from a baseline of 12.1 in the placebo group. There was also a lower heart rate seen in the treatment group. This study was led by the company producing the DHA supplement and was not a double blind study but had a randomized design. There were few adverse effects reported(P=.032). (26)
Lee, LK et al performed a relatively small randomised, double-blind, placebo-controlled study on 36 subjects which tested the cognitive function of elderly subjects with mild cognitive impairment. The trial used 3, 1 gram gelatin capsules of fish oil given per day, each containing 430 mg of DHA and 150 mg of EPA or equivalent calorie placebo for 12 months. The fish oil group showed a significant benefit in working memory, short term memory, better recall memory, and improved immediate verbal memory. The fish oil was well tolerated with minimal adverse effects which were self limited. (27)
A study by Quinn JF et al evaluated 295 subjects as part of a randomized, double-blind, placebo-controlled trial for cognitive decline in mild to moderate Alzhiemer’s disease. Subjects took 2 grams of algal DHA or placebo for 18 months. The groups were tested by using the Alzheimer’s Disease Assessment Scale for Cognition (ADAS-Cog). There was no improvement seen on the testing and the DHA did not show any evidence of slowing the functional or cognitive decline in Alzheimer’s disease. (28)
Studies show mixed conclusions in the use of Ginkgo biloba for Alzheimer’s Disease:
Ginkgo biloba extract (GBE) was not significantly effective in reducing dementia in a study that included 118 older participants (aged 85 and older) who were followed for 3.5 years. GBE did not reduce risk of progression of dementia nor did it reduce decline in memory. (31)
Ginkgo biloba (GB) was not effective in preventing the onset of mild cognitive impairment (MCI) or Alzheimer’s disease (AD) or MCI developing into AD. Study participants (normal cognition, n = 2587 or MCI, n = 482) aged 75 or older (mean 79 years) taking 120 mg twice daily of GB over 6.1 years, showed no benefit for all-cause dementia nor for AD specifically. A total of 523 patients were diagnosed with dementia during the course of the study including 246 (16.1%) in the placebo group and 277 (17.9%) in the GB group; 92% of those with dementia were classified as Alzheimer’s disease (AD). The rate of development of all cause dementia did not significantly differ between the two groups nor did the rates of development of. GB did not significantly affect the rate of progression to dementia in those with MCI at the start of the study. (32)
Results from 3 modern trials showed inconsistent evidence that Ginkgo has a significant benefit for people with dementia or cognitive impairment. However, review of other studies showed a cognitive benefit and improvement in activities of daily living with Ginkgo, compared to placebo, at 12 weeks (dose < 200 mg/d), 24 weeks (dose > 200 mg/d), and 52 weeks (dose < 200 mg/d). Mood and emotion well being increased with Ginkgo, compared to placebo, at less than 12 weeks (dose < 200 mg/d ) and at 12 weeks at (dose > 200 mg/d). No serious side-effects were reported with use of Ginkgo. (33)
Ginkgo biloba (EGb 761) at a dose of 120 mg/day was believed to be safe according to a study by Le Bars, PL et al. It was stated that the herbal agent appears to improve the cognitive performance and the social functioning of dementia in participants with Alzheimer’s disease (AD) (n=309). Changes associated with EGb were measured by the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Geriatric Evaluation by Relative’s Rating Instrument (GERRI), and Clinical Global Impression of Change (CGIC). Findings show that the EGb group had significantly better ADAS-Cog and GERRI scores than placebo of 1.4 points and 0.14 points, respectively. Additionally, 27% of patients in the EGb group reached a 4-point improvement on the ADAS-Cog (vs 14% with placebo). On the GERRI, 37% were considered improved with EGb (vs 23% with placebo). No difference was seen in the CGIC. EGb was as well tolerated as placebo. (34)
Ginkgo biloba appears to be more effective than placebo in Alzheimer’s disease. A meta-analysis reviewed nine trials lasting 12 to 52 weeks included a total of 2,372 patients with Alzheimer’s disease or another form of dementia were evaluated to determine the efficacy of ginkgo biloba on cognitive function. Those in the ginkgo group did have improvements in their cognition scores. Changes in cognition were in favor of Ginkgo when compared with placebo, although the difference was not as significant for activities of daily living. Most of the studies reviewed showed a greater benefit with a dosage of 240 mg of ginkgo compared with a 120 mg dose. Only one of the studies reviewed showed benefit over placebo in cognition and activities of daily living. Discontinuation of ginkgo was 1-6% due to side effects. The reviewers concluded that Ginkgo biloba appears more effective than placebo. (25)
Creatine and cognitive function:
A study of 32 older people revealed that creatine supplementation aids cognition in the elderly. Participants were divided into two groups, Group 1 (n = 15) were given 5 g four times a day of placebo for 1 week, followed by the same dosage of creatine for the second week and group 2 (n = 17) were given placebo both weeks. All participants were tested on random number generation, forward and backward number and spatial recall, and long-term memory tasks to establish a baseline level. Participants were retested at the end of each week. Findings showed a significant positive effect of creatine supplementation on all tasks except backward number recall. (23)
Alpha lipoic acid (ALA) and Alzheimer’s disease:
Alpha lipoic acid (ALA) may help to slow down Alzheimer’s progression in people already diagnosed with the disease. One study found that alpha lipoic acid may help protect against Alzheimer’s by preventing free radical production. In one study, a daily dose of 600 mg of ALA was given to 9 patients with Alzheimer’s disease and after a year, the ALA helped to stabilize their cognitive function as measured by two neuropsychological tests (the mini mental state exam, MMSE and the Alzheimer’s disease assessment score cognitive subscale, ADAScog). During a larger and longer follow-up study that included 43 patients observed for up to 48 months, the progression of the disease was dramatically lower among those taking ALA compared to those getting no treatment or those taking conventional Alzheimer drugs. In patients with mild dementia ADAScog increased by 1.2 points/year and MMSE decreased by 0.6 points/year. The results were about twice these rates in patients with moderate dementia. (24)
Idebenone and Alzheimer’s disease:
In a randomized, double-blind, multicenter human study, 450 patients with mild to moderate dementia were given either placebo for 12 months, followed by 90 mg idebenone (an organic quinone compound and a different form of Coenzyme Q10) three times per day for another 12 months; 90 mg three times per day for 24 months; or 120 mg three times per day for 24 months. Significant dose-dependent improvements were seen in measurements of clinical cognitive status and tests (including the Alzheimer’s Disease Assessment Scale [ADAS-Total], ADAS cognitive and noncognitive score, the clinical global response) compared to placebo. As the dose of idebenone increased so did the benefits. These improvements continued over the 2-year study. (35)
Zinc and Alzheimer’s disease:
Over a placebo, zinc given to zinc deficient elderly patients age 70 and older at a dose of 150 mg oral daily (unknown zinc formula) for 6 months resulted in protection from cognitive decline after assessed by three different scoring methods including the Alzheimer’s Disease Assessment Scale, cognitive subsection (ADAS-Cog), Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB), and the mini–mental state examination (MMSE) scores. The results were statistically significant for the ADAS-Cog and CDR-SOB scores, but not for the MMSE scores. Zinc levels in the Alzheimer’s patients were found to be about 8% lower than age-matched controls and about 24% lower than young adults on average. Copper is believed by the authors of the study to oxidize molecules which become toxic to neurons. The protection in cognitive decline by the zinc supplement was believed to be either restoration of neuronal zinc levels or reduction in serum copper levels by the zinc supplement or both. (36)
Ashwagandha and Cognitive Function
Kuboyama T et al found that withanolide A isolated from Ashwagandha root was able to regenerate axons, dendrites, and synapses in mice with brain damage. Further testing on whether Ashwagandha root improves cognitive function is needed.
Summary: Memory Enhancement, Cognitive Impairment, Dementia, and Alzheimer’s Disease
- All adults and children should maintain an adequate B12 level by having it checked by a primary physician if at risk of deficiency. The normal range of 200 – 900 pg/ml (at least over 200 pg/ml) but levels of 200 – 500 pg/ml have been associated with deficiency symptoms especially in older adults. Patients with higher risk of B12 deficiency include vegetarians, elderly, those with anemia or any chronic diseases, and those with alcohol abuse. Vitamin B12 dose should be 250 mcg oral per day or 2500 mcg oral per week to ensure adequate allowances. B12 is water soluble, not dangerous in excess which is eliminated by the kidneys via urine. Please see the section of vitamin B12. More information on B12 is also available at MedlinePlus here: http://www.nlm.nih.gov/medlineplus/ency/article/003705.htm
- Have your homocysteine level checked. Elevated homocysteine (hyperhomocysteinemia) is a risk factor for neurodegenerative diseases and supplementation with folic acid, vitamin B6, and vitamin B12 or consuming more foods with these nutrients can decrease homocysteine levels.
- Research has found that those who have consumed the following foods have had a lower risk of dementia and a slower rate of cognitive decline: carrots, cruciferous vegetables (broccoli, cabbage, kale and brussel sprouts), citrus fruits, whole grain breads, tea, red wine, vegetable juice, green leafy vegetables, strawberries, apples, grapes, and onions. Three servings or more which total at least 200 grams by weight (7 oz.) of vegetables per day but the strongest cognitive performance was seen at a range of 500 grams of vegetables or more per day (18 oz.).
- Blueberry juice may be beneficial as seen in the study mentioned above using 444 ml to 621 ml per day based on weight or could consider eating blueberries at an unknown equivalent to juice.
- In one study, fish consumption of once per week or more in the form of fresh fish, tuna, fish cakes, fish sticks and fish sandwiches was associated with reduced risk of Alzheimer’s disease.
- Aerobic exercise improves cognitive function, cognitive impairment, and has resulted in less brain tissue loss.
- Individuals with many years of previous daily caffeine intake of 198.7 mg per day were found to have less Alzheimer’s dementia than those who had 73.9 mg of caffeine per day with multiple studies quoting coffee as beneficial and one study quoting 3 -5 cups per day as beneficial. Caffeine intake is generally recognized as safe by the FDA and AMA but can be dangerous with adverse effects such as high bp, stroke, and arrythmias reported. If more than 1-2 cups of caffeinated beverages are consumed per day, it is prudent to seek physician and/or pharmacist approval of caffeine consumption with any medications or supplements.
- Up to 3 servings of wine daily and moderate alcohol use was associated with a lower AD risk compared to nondrinkers and alcohol abusers. Physicians are reluctant to recommend alcohol intake even for health reasons. Prior to considering alcohol use daily or several times per week, discuss the risks and health benefits with the primary physician.
- Saffron at a dose of 15 mg twice per day was both safe and effective in mild to moderate Alzheimer’s disease with minimal adverse effects and was similar in benefit to Aricept (donepezil) but there is only 2 studies so far. Saffron has not been studied in those with mild cognitive impairment.
- Fish oil at a dose of 3g daily or algal DHA (docosahexaenoic acid) at a dose of 900 mg per day were shown in some studies to improve cognitive impairment in older patients, but not all studies showed benefit. This supplement is relatively safe but may be associated with an increased anticoagulation (reduce blood clotting) effect. Consumption should be avoided when taking anticoagulants like aspirin, warfarin, non-steroidal anti-inflammatory drugs (NSAIDs), or ticlopidine because of the potential increased risk of bleeding. There has also been recent controversy regarding presence of polychlorinated biphenyls (PCBs) in fish oil which is regarded as a possible carcinogen. Algal DHA does not contain PCBs and is the safest form of DHA until the controversy has been thoroughly addressed. However, most fish oil supplements are distilled to remove at least mercury and recently, companies have begun purifying it to remove PCBs and dioxins also. A 2008 report released by Consumer Reports did not find PCBs, dioxins, or mercury in several tested fish oil brands.
- Alpha lipoic acid (ALA) has not been studied in any randomized controlled trials to date.
- Creatine has some benefit in cognitive function but is not yet well studied. Patients have often described subjective improvement.
- Ginkgo biloba study results have been mixed and unfortunately the studies which showed cognitive benefit used higher doses which are more likely to cause harm. Risk of bleeding outweighs the benefit of using this supplement. Ginkgo has been reported to cause spontaneous bleeding in the brain and may interact with non-steroidal anti-inflammatory drugs (NSAIDs), warfarin (Coumadin), heparin, aspirin, and other anti-platelet drugs to increase risk of bleeding.
- Zinc and Alzheimer’s disease: Over a placebo, zinc given to zinc deficient elderly patients age 70 and older at a dose of 150 mg oral daily (unknown zinc formula) for 6 months resulted in protection from cognitive decline believed due to either restoration of neuronal zinc levels or reduction in serum copper levels by the zinc supplement or both (36).
- Kuboyama T et al found that withanolide A isolated from Ashwagandha root was able to regenerate axons, dendrites, and synapses in mice with brain damage. Further testing on whether Ashwagandha root improves cognitive function is needed.
References :
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