Alzheimer’s Disease

What is Alzheimer’s Disease?

Alzheimer’s is a progressive neurodegenerative brain disorder and the most common type of dementia among older people. With Alzheimer’s, the destruction and death of nerve cells leads to memory failure, personality changes, and eventually leads to loss of even the simplest tasks of daily life.

Causes and Symptoms

Scientists don’t know exactly what causes Alzheimer’s, but research indicates that the causes include some mix of genetic, environmental, and lifestyle factors. What they do know is that during the early stages of the disease there are few obvious symptoms – even though physical changes are occurring in the brain. Those changes include a buildup of abnormal amyloid plaques and bundles of neurofibrillary tangles that may start as early as 20 years old.[1]

Once-healthy neurons in the brain begin to work less efficiently. Over time, those neurons lose their ability to function and communicate with each other, and eventually they die and the brain shrinks. The damage also spreads to the brain’s hippocampus, which is the primary area where new memories are formed.

Scientists are studying age-related changes in the brain that may harm neurons and contribute to Alzheimer’s damage. These age-related changes include shrinking of certain parts of the brain, inflammation, the production of unstable free radicals, along with the breakdown of mitochondrial energy production within a cell.
Genetics also play a role. Many studies have linked the apolipoprotein E (APOE) gene to late-onset Alzheimer’s. This gene has several forms including APOE ε4, which seems to increase a person’s risk of getting the disease.

Studies also indicate there may be associations between cognitive decline, vascular, and metabolic conditions such as heart disease, stroke, high blood pressure, diabetes, and obesity.

Symptoms and warning signs of Alzheimer’s may include:

  • Memory loss that disrupts daily life
  • Challenges in planning or solving problems
  • Difficulty completing familiar tasks at home, at work or at leisure
  • Confusion with time or place, wandering, anxiety, sleeplessness
  • Trouble understanding visual images and spatial relationships
  • New problems with words in speaking or writing
  • Misplacing things and losing the ability to retrace steps
  • Decreased or poor judgment
  • Withdrawal from work or social activities
  • Changes in mood and personality

Note: Having trouble with memory does not necessarily indicate onset of Alzheimer’s. Some cognitive decline and memory loss is a natural part of aging. There are a number of health issues that can affect memory and thinking, including depression, drug interactions, thyroid problems, excess use of alcohol, or certain vitamin deficiencies.

Diagnosis

There is no one test that clearly confirms Alzheimer’s. Diagnosing Alzheimer’s requires careful medical evaluation, including:

  • A thorough medical history
  • Mental status testing
  • A physical and neurological exam
  • Blood tests
  • Brain imaging to rule out other causes like stroke or tumor
  • Tests of memory, problem solving, attention, counting, and language

Risk Factors

About 70 percent of the risk is believed to be genetic with many genes  involved. Other risk factors include: a history of head injuries or head trauma, depression, hypertension, and mild cognitive impairment.

There is some evidence suggesting that the risk factors of heart disease may also increase the risk of developing Alzheimer’s, including:

  • Lack of exercise
  • Poorly controlled diabetes
  • Smoking
  • Elevated homocysteine levels
  • High blood pressure
  • High blood cholesterol
  • A diet lacking in fruits and vegetables

Management

While there is no cure for Alzheimer’s, early diagnosis is important because there are treatments that may help preserve function for a while. An early diagnosis can also help families and patients create a support network and make plans for the future to deal with housing arrangements, financial, legal matters, and long-term care.

Pharmacological Treatment

There are currently five medications approved by the U.S. Food and Drug Administration to treat Alzheimer’s disease:

  • Cholinesterase inhibitors these drugs work by inhibiting the breakdown of acetylcholine (a brain neurotransmitter). Examples include: donepezil, galantamine, rivastigmine and tacrine.
  • NMDA receptor antagonists work by blocking NMDA (N-methyl-D-aspartate) Over-expression of glutamate in Alzheimer’s disease leads to calcium-mediated cellular damage, inhibition of NMDA receptors blocks the release of calcium.

Unfortunately, these drugs only work for a limited time and don’t alter the disease process or progress. They’re also not always effective for all people.

Natural Approaches

Studies indicate certain lifestyle choices may help reduce the risk of cognitive decline and Alzheimer’s disease including:

  • Lifelong learning and social engagement
  • A stimulating job
  • Mentally challenging leisure pursuits like reading, learning a language, playing games or playing a musical instrument
  • Frequent social interactions

It is also important to eat a nutritious diet where most calories consist of vegetables, along with a consuming very little saturated/trans fats.[2] Regular physical activity has also been shown to both prevent cognitive decline and help people who already have Alzheimer’s.[3] Maintaining healthy blood sugar levels is also considered important to preventing Alzheimer’s.[4]

Acetyl-L-carnitine (ALC)

Acetyl-L-carnitine (ALC) is a non-essential amino acid derivative that can act as a partial direct cholinergic agonist and can also be converted into acetylcholine (neurotransmitter). These actions, along with some neuroprotective actions reported in several pilot studies on chemotherapy-induced nerve toxicity[5] have led to the suggestion that ACL may be neuroprotective and effective in Alzheimer’s patients. A 2003 meta-analysis, covering 21 randomized placebo-controlled trials (covering 1204 subjects), using 1.5 to 3.0 g ALC per day for 3-12 months for both Alzheimer’s and mild cognitive impairment reported significant benefit for all conditions, although the effect size was modest.[6] Another 2003 review suggested that there is no evidence for the benefit of ALC, except for improvement in clinical global impression, but this may a chance finding.[7]

Antioxidants

It is fairly clear that lifelong dietary antioxidant intake reduces risk of Alzheimer’s disease. A 2002 study published in JAMA correlated high dietary intakes of vitamin C and vitamin E in foods with a relative risk reduction of around 18 percent.[8] A sub-study also suggested that vitamin E from food was associated with risk reduction, but only in persons with APOE epsilon 4 allele.[9] Confounders are many in these studies, with foods high in vitamin C and E often high in other antioxidants, polyphenols, and other bioactive components.

Supplemental studies have showed varying results. A 1998 study of 633 elderly (over 65) who were followed for an average of 4.3 years demonstrated dramatic reductions in Alzheimer’s for persons supplementing with vitamin E and C.[10] A 2003 study of 980 persons[11] and a 2008 study of 2969 participants[12] both found no relationship between supplement users and non-users. A 2004 study of 4740 respondents correlated supplementing with vitamin E and C with a 22 percent reduced odds ratio.[13] All of these intervention trails are generally short (3-5 years) and have studied elderly populations, it would be interesting to study life-long use to antioxidants and their relationship to Alzheimer’s.

B vitamins

B vitamins are essential co-factors in numerous reactions and play a strong role in nerve health and condition. Deficiencies in B vitamins are well known to result in any number of neurological conditions.

  • B12 and Folic Acid: these two vitamins are often tested together because of their ability to lower homocysteine levels. A 2003 Cochrane review of eight randomly controlled trials had difficulty pooling data due to differing dosages, trial duration, and population selection. They were able, however, to point to some benefits seen in people with high homocysteine levels treated with 800 mcg/day of folic acid, reporting improvements in global functioning, memory storage, and information processing speed. Another trial using 1 mg/day folic acid along with cholinesterase inhibitors demonstrated significant improvements in Instrumental Activities of Daily Living and Social behavior. Other trials showed no effects.[14]
  • Thiamine: High dose oral thiamine 3-8 grams/day has shown some mild benefits in one small study.[15] A 2001 review found very little evidence for the effectiveness of thiamine in symptoms of Alzheimer’s disease.[16]

CoQ10

Coenzyme Q10 (CoQ10) is both an antioxidant and a component of the mitochondrial electron transport chain (energy production). Oxidative stress and its resulting depletion of glutathione has been implicated in multiple neurodegenerative disorders (Alzheimer’s, Parkinson’s…) and a deficit in CoQ10 has also been determined in many of these disorders.[17] CoQ10 has been used in pre-clinical models and shown to reduce amyloid pathology.[18] To date, no significant human trials of CoQ10 has been undertaken, but its use may be warranted by the available pre-clinical evidence, known mechanism of action, and the low side effect profile of CoQ10. [19]

Fish Oil

The brain is an organ rich in lipid. Both DHA and EPA can make up a large part of the composition of the normal brain and play a role in reducing inflammation. [20] Many longitudinal studies observe inverse relationships between cognitive impairment later in life and fish intake and/or serum concentration of EPA/DHA.[21] Intervention studies, however, have had conflicting results. EPA/DHA seems to be helpful in those with mild cognitive impairment, but supplementing those with already established Alzheimer’s has largely been unsuccessful.[22] An interesting 2014 study showed that fish oil supplementation was associated with both preservation of cognition and brain volume in people without signs of disease, but only in APOE ε4-negative participants.[23] Clearly, it is best to start early with either supplementation or ensuring a diet strong in fish.

Ginkgo

Ginkgo is probably the best studied of the natural approaches to Alzheimer’s disease. While certainly not a cure-all, standardized Ginkgo extracts do appear to provide modest improvements in cognitive measures with effect size better than placebo and comparable to standard treatment (cholinesterase inhibitors).[24] A 2013 meta-analysis of six studies meeting inclusion criteria totaling 1917 patients concluded that Ginkgo was superior to placebo in prevention of cognitive decline and maintenance of activities of daily living, but only for subject younger than 75 years old.[25]

Ginseng

Ginseng has a long history in Chinese medicine of use in for mental defense against aging. A 2010 Cochrane reviewed nine placebo controlled, randomized, double blind, studies that met inclusion criteria. Results of analysis reported some improvements in aspects of cognitive function, quality of life, and behavior – even though pooling of data was impossible due to differing products, dosing regimens, and endpoints.[26]

Other Professional Resources

Alzheimer’s Disease Fact Sheet

Alzheimer’s Association

 

References

[1] Baker-Nigh A, Vahedi S, Davis EG, Weintraub S, Bigio EH, Klein WL, Geula C. Neuronal amyloid-β accumulation within cholinergic basal forebrain in ageing and Alzheimer’s disease. Brain. 2015 Mar 1. PMID: 25732182.

[2] Barnard ND, Bush AI, Ceccarelli A, et al. Dietary and lifestyle guidelines for the prevention of Alzheimer’s disease. Neurobiol Aging. 2014 Sep;35 Suppl 2:S74-8. PMID: 24913896.

[3] Kirk-Sanchez NJ, McGough EL. Physical exercise and cognitive performance in the elderly: current perspectives. Clin Interv Aging. 2014;9:51-62. PMID: 24379659.

[4] Sebastião I, Candeias E, Santos MS, et al. Insulin as a Bridge between Type 2 Diabetes and Alzheimer Disease – How Anti-Diabetics Could be a Solution for Dementia. Front Endocrinol (Lausanne). 2014 Jul 8;5:110. PMID: 25071725.

[5] De Grandis D. Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review. CNS Drugs. 2007;21 Suppl 1:39-43. PMID: 17696592.

[6] Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer’s disease. Int Clin Psychopharmacol. 2003 Mar;18(2):61-71. PMID: 12598816.

[7] Hudson S, Tabet N. Acetyl-L-carnitine for dementia. Cochrane Database Syst Rev. 2003;(2):CD003158. PMID: 12804452.

[8] Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, Breteler MM. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA. 2002 Jun 26;287(24):3223-9. PMID: 12076218.

[9] Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Wilson RS, Scherr PA. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA. 2002 Jun 26;287(24):3230-7. PMID: 12076219.

[10] Morris MC, Beckett LA, Scherr PA, Hebert LE, Bennett DA, Field TS, Evans DA. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord. 1998 Sep;12(3):121-6. PMID: 9772012.

[11] Luchsinger JA, Tang MX, Shea S, Mayeux R. Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol. 2003 Feb;60(2):203-8. PMID: 12580704.

[12] Morris MC, Beckett LA, Scherr PA, Hebert LE, Bennett DA, Field TS, Evans DA. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord. 1998 Sep;12(3):121-6. PMID: 9772012.

[13] Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004 Jan;61(1):82-8. PMID: 14732624.

[14] Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD004514.PMID: 18843658.

[15] Meador K, Loring D, Nichols M, Zamrini E, Rivner M, Posas H, Thompson E, Moore E. Preliminary findings of high-dose thiamine in dementia of Alzheimer’s type. J Geriatr Psychiatry Neurol. 1993 Oct-Dec;6(4):222-9. PMID: 8251051.

[16] Rodríguez-Martín JL, Qizilbash N, López-Arrieta JM. Thiamine for Alzheimer’s disease. Cochrane Database Syst Rev. 2001;(2):CD001498. PMID: 11405995.

[17] Mancuso M, Orsucci D, Volpi L, Calsolaro V, Siciliano G. Coenzyme Q10 in neuromuscular and neurodegenerative disorders. Curr Drug Targets. 2010 Jan;11(1):111-21. PMID: 20017723.

[18] Dumont M, Kipiani K, Yu F, Wille E, Katz M, Calingasan NY, Gouras GK, Lin MT,

Beal MF. Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis. 2011;27(1):211-23. PMID: 21799249.

[19] Young AJ, Johnson S, Steffens DC, Doraiswamy PM. Coenzyme Q10: a review of its promise as a neuroprotectant. CNS Spectr. 2007 Jan;12(1):62-8. PMID: 17192765.

[20] Freund-Levi Y, Vedin I, Hjorth E, et al. Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer’s disease: the OmegAD study. J Alzheimers Dis. 2014;42(3):823-31 PMID: 24934544.

[21] Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Fish consumption and cognitive decline with age in a large community study. Arch Neurol. 2005 Dec;62(12):1849-53. Epub 2005 Oct 10. PMID: 16216930.

[22] Cederholm T, Salem N Jr, Palmblad J. ω-3 fatty acids in the prevention of cognitive decline in humans. Adv Nutr. 2013 Nov 6;4(6):672-6. PMID: 24228198.

[23] Daiello LA, Gongvatana A, Dunsiger S, Cohen RA, Ott BR; Alzheimer’s Disease Neuroimaging Initiative. Association of fish oil supplement use with preservation of brain volume and cognitive function. Alzheimers Dement. 2014 Jun 18. PMID: 24954371.

[24] Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD003120. PMID: 19160216.

[25] Jiang L, Su L, Cui H, Ren J, Li C. Ginkgo biloba extract for dementia: a systematic review. Shanghai Arch Psychiatry. 2013 Feb;25(1):10-21. PMID: 24991128.

[26] Geng J, Dong J, Ni H, Lee MS, Wu T, Jiang K, Wang G, Zhou AL, Malouf R. Ginseng for cognition. Cochrane Database Syst Rev. 2010 Dec 8;(12):CD007769. PMID: 21154383.