More than five million Americans suffer from Alzheimer's, according to the National Institutes of Health.
And more than 16 million will have the disease by 2050, according to Alzheimer's Association estimates, resulting in medical costs of over $1 trillion per year.
Alzheimer's typically appears after age 60, although a small percentage of families carry a genetic risk for earlier onset.
Among the top ten causes of death, Alzheimer's is the only one without a way to prevent, cure, or slow down disease progression.
Over the past decade, studies in rodents have found that omega-3 fish oil and blueberries exert beneficial effects in these animals' brains … benefits that may be relevant to prevention or amelioration of Alzheimer's disease.
These rat and mouse studies also showed that one omega-3 in particular – DHA, which is essential to animal and human brain structure and functions alike – helped rodents' brains withstand physical or psychological brain trauma more resiliently.
Specifically, these experiments revealed that even short-term feeding of omega-3 fish oil “up-regulated” growth of new brain cells (Beltz BS et al. 2007) in rodents.
Another team found that adding omega-3 DHA to brain cells taken from the hippocampus – the brain's memory-forming center – enhanced connectivity among these neurons via increased “extension and branching” (Calderon F et al. 2004).
And a third group reported that fish oil raised rodents' brain levels of brain-derived neurotrophic factor (BDNF) … a key compound that promotes survival and growth of brain cells (Wu A et al. 2004).
On a cellular level, a DHA-enriched diet increased levels of six beneficial chemicals, which enhance the brain “plasticity” needed for memory and learning:
- BDNF (brain-derived neurotrophic factor)
- Mature BDNF
- CREB (cAMP responsive element-binding protein)
- Synapsin I
- Hippocampal Akt
- Hippocampal CaMKII
Berries and company yield similar brain benefits
And the authors of this research believe that these effects extend to most berries, because they flow from certain polyphenols (antioxidants) called anthocyanins and flavanols, which abound in almost all berries … as well as in dark chocolate, natural (non-Dutched) cocoa, and grapes.
We also know that these particular polyphenols exert beneficial “nutrigenomic” effects on genetic switches called nuclear transcription factors, such as Nf-kappaB (Goyarzu P et al. 2004).
Specifically, they tend to “turn off” pro-inflammatory genetic switches, and may thereby inhibit the chronic low-level inflammation associated with Alzheimer's and other degenerative diseases.
In both trials, people who drank blueberry juice or smoothies showed significant improvements in learning and memory, compared with the control groups, and showed a statistical trend towards fewer signs of depression, and lower blood sugar (glucose) levels.
New Alzheimer's drug may prevent disease progression
Now, scientists at the Salk Institute for Biological Studies say they've developed a new drug that improves memory and prevents brain damage in mice.
Remarkably, it works by exerting effects similar to those that omega-3 fish oil and blueberries displayed in rodent studies.
When given to mice with Alzheimer's, an experimental drug called J147 improved memory and prevented brain damage caused by the disease (Chen Q et al. 2011).
According to David Schubert, director of Salk's Cellular Neurobiology Laboratory, “J147 enhances memory in both normal and Alzheimer's mice and also protects the brain from the loss of synaptic connections. No drugs on the market for Alzheimer's have both of these properties.”
That is certainly true of current Alzheimer's drugs … but as we've just described, berries and omega-3 DHA seem to bring these same benefits to rodents' brains.
So far, the drugs developed to treat the disease – such as Aricept, Razadyne, and Exelon – only produce slight, fleeting memory improvements and do nothing to slow the overall course of the disease.
All of these drugs belong to a family called “cholinesterase inhibitors”, which reduce breakdown of a brain compound called acetylcholine that mediates communication between neurons (brain cells), and whose production is reduced by the presence of amyloid plaque (Pedersen WA et al. 1996).
To date, academic and pharmaceutical industry researchers have focused almost exclusively on drugs that block the actions of cholinesterase … an enzyme that the brain uses to break down excess acetylcholine.
Since the brain cells of Alzheimer's patients don't produce enough acetylcholine, the goal of using cholinesterase inhibitor drugs is to curb the enzymatic process by which the brain normally breaks down acetylcholine.
Sadly, none of the existing amyloid-based drugs have produced substantial benefits in clinical trials … probably because reduced production of acetylcholine isn't the primary problem in Alzheimer's disease.
As the authors of one evidence review wrote, “The debate on whether donepezil [Aricept] is effective continues despite the evidence of efficacy from the clinical studies because the treatment effects are small and are not always apparent in practice.” (Birks J, Harvey RJ 2006)
Experimental drug echoes omega-3s' brain effects
Instead of targeting cholinesterase, the Salk team used living neurons to test whether or not new synthetic compounds were effective at protecting the brain cells against changes associated with Alzheimer's.
Based on the results of testing chemical variations on a compound originally developed for treatment of stroke and traumatic brain injury, they were able to make it into a much more potent anti-Alzheimer's drug … at least in animals.
The Salk researchers conducted a range of behavioral tests, which showed that J147 improved memory in normal rodents.
The scientists went on to show that it prevented cognitive decline in animals with Alzheimer's and that mice and rats treated with the drug produced more brain-derived neurotrophic factor (BDNF).
As we said, omega-3 DHA is also shown to raise brain levels of BDNF, which protects neurons from damage, helps new neurons grow and connect with other brain cells, and is involved in memory formation.
Because of the broad ability of J147 to protect nerve cells, the researchers believe that it may also be effective for treating other neurological disorders, such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS), as well as stroke.
The Salk team hopes to test the new compound in humans in the near future. (Their research was supported by the National Institutes of Health and the Alzheimer's Association, among funders.)
In the meantime, it seems logical to fill your diet with fatty fish and/or fish oil, as well as berries and other sources of the flavanol-type antioxidants that appear to produce their brain benefits … including tea, dark chocolate, natural, non-Dutched cocoa, and grapes.
While it may well be that none of these foods can produce brain-protective effects as potent as a synthetic drug like J147 – assuming it actually works in people – they bring multiple health benefits and have no adverse effects.
We should also note that animal experiments support the possible efficacy of Krill oil (Lee B et al. 2010) … and of a traditional Chinese herb called Rehmannia (Rehmannia glutinosa or “Chinese Foxglove”).
Like omega-3 DHA, flavanols, and J147, Rhemannia root boosts brain levels of BDNF. It's shown to significantly improve memory deficits in rodents with Alzheimer's (Liu J et al. 2006; Wang Z et al. 2009; Lee B et al. 2011)
Andres-Lacueva C, Shukitt-Hale B, Galli RL, Jauregui O, Lamuela-Raventos RM, Joseph JA. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci. 2005 Apr;8(2):111-20.
Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD001190. Review.
Bousquet M, Gibrat C, Saint-Pierre M, Julien C, Calon F, Cicchetti F. Modulation of brain-derived neurotrophic factor as a potential neuroprotective mechanism of action of omega-3 fatty acids in a parkinsonian animal model. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1401-8. Epub 2009 Jul 24.
Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem. 2004;90(4):979-988.
Cantu RC. Chronic traumatic encephalopathy in the National Football League. Neurosurgery. 2007 Aug;61(2):223-5. Review.
Chance R. Food for Thought. British Science Association, September 14, 2009. Accessed at http://www.britishscienceassociation.org
Chen Q, Prior M, Dargusch R, Roberts A, Riek R, Eichmann C, Chiruta C, Akaishi T, Abe K, Maher P, Schubert D. A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease. PLoS One. 2011;6(12):e27865. Epub 2011 Dec 14.
Cotman CW, Engesser-Cesar C. Exercise enhances and protects brain function. Exerc Sport Sci Rev. 2002 Apr;30(2):75-9. Review.
Cysneiros RM, Ferrari D, Arida RM, Terra VC, de Almeida AC, Cavalheiro EA, Scorza FA. Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids. Epilepsy Behav. 2010 Jan;17(1):33-8. Epub 2009 Dec 6.
Derbyshire D. A bowl of blueberries keeps the brain active in the afternoon. The Daily Mail UK, September 14, 2009. Accessed at http://www.dailymail.co.uk/
Dishman RK, Berthoud HR, Booth FW, Cotman CW, Edgerton VR, Fleshner MR, Gandevia SC, Gomez-Pinilla F, Greenwood BN, Hillman CH, Kramer AF, Levin BE, Moran TH, Russo- Feng R, Rampon C, Tang YP, et al. Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron. 2001;32(5):911-926.
Garcia P, Youssef I, Utvik JK, Florent-Béchard S, Barthélémy V, Malaplate-Armand C, Kriem B, Stenger C, Koziel V, Olivier JL, Escanye MC, Hanse M, Allouche A, Desbène C, Yen FT, Bjerkvig R, Oster T, Niclou SP, Pillot T. Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease. J Neurosci. 2010 Jun 2;30(22):7516-27.
Kitamura T, Saitoh Y, Takeshima N, et al. Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell. 2009;139(4):814-827.
Krikorian R, Nash TA, Shidler MD, Shukitt-Hale B, Joseph JA. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2009 Dec 23:1-5. [Epub ahead of print]
Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, Joseph JA. Blueberry Supplementation Improves Memory in Older Adults (dagger). J Agric Food Chem. 2010 Jan 4. [Epub ahead of print]
Lee B, Shim I, Lee H, Hahm DH. Rehmannia glutinosa ameliorates scopolamine-induced learning and memory impairment in rats. J Microbiol Biotechnol. 2011 Aug;21(8):874-83.
Lee B, Sur BJ, Han JJ, Shim I, Her S, Lee HJ, Hahm DH. Krill phosphatidylserine improves learning and memory in Morris water maze in aged rats. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Aug 16;34(6):1085-93.
Liu J, He QJ, Zou W, Wang HX, Bao YM, Liu YX, An LJ. Catalpol increases hippocampal neuroplasticity and up-regulates PKC and BDNF in the aged rats. Brain Res. 2006 Dec 6;1123(1):68-79. Epub 2006 Oct 31.
Logan AC. Omega-3 and BDNF regulation: eicosapentaenoic acid may play a key role in limitation of CNS injury. J Neurotrauma. 2008 Dec;25(12):1499. No abstract available.
Macready AL, Kennedy OB, Ellis JA, Williams CM, Spencer JP, Butler LT. Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies. Genes Nutr. 2009 Dec;4(4):227-42. Epub 2009 Aug 13.
Matsuoka Y, Nishi D, Nakajima S, Yonemoto N, Hashimoto K, Noguchi H, Homma M, Otomo Y, Kim Y. The Tachikawa cohort of motor vehicle accident study investigating psychological distress: design, methods and cohort profiles. Soc Psychiatry Psychiatr Epidemiol 2009, 44:341.
Matsuoka Y, Nishi D, Yonemoto N, Hamazaki K, Hamazaki T, Hashimoto K. Potential role of BDNF in the omega-3 fatty acid supplementation to prevent posttraumatic distress after accidental injury: An open-label pilot study. Psychothear Psychosom in press.
Matsuoka Y, Nishi D, Yonemoto N, Hamazaki K, Hashimoto K, Hamazaki T. Omega-3 fatty acids for secondary prevention of posttraumatic stress disorder after accidental injury: an open-label pilot study. J Clin Psychopharmacol. 2010 Apr;30(2):217-9.
Neustadt AA, Salamone JD, Van Hoomissen JD, Wade CE, York DA, Zigmond MJ. Neurobiology of exercise. Obesity (Silver Spring). 2006 Mar;14(3):345-56. Review.
Peters J, Dieppa-Perea LM, Melendez LM, Quirk GJ. Induction of Fear Extinction with Hippocampal-Infralimbic BDNF. Science 2010, 328:1288-1290. Rao JS, Ertley RN, Lee HJ, DeMar JC Jr, Arnold JT, Rapoport SI, Bazinet RP. n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism. Mol Psychiatry. 2007 Jan;12(1):36-46. Epub 2006 Sep 19.
Spencer JP. Flavonoids and brain health: multiple effects underpinned by common mechanisms. Genes Nutr. 2009 Dec;4(4):243-50. Epub 2009 Aug 15. Squire LR. Memory and Brain. Oxford: Oxford University Press; 1987.
Venna VR, Deplanque D, Allet C, Belarbi K, Hamdane M, Bordet R. PUFA induce antidepressant-like effects in parallel to structural and molecular changes in the hippocampus. Psychoneuroendocrinology. 2009 Feb;34(2):199-211. Epub 2008 Oct 10.
Wang Z, Liu Q, Zhang R, Liu S, Xia Z, Hu Y. Catalpol ameliorates beta amyloid-induced degeneration of cholinergic neurons by elevating brain-derived neurotrophic factors. Neuroscience. 2009 Nov 10;163(4):1363-72. Epub 2009 Jul 24.
Williams CM, El Mohsen MA, Vauzour D, Rendeiro C, Butler LT, Ellis JA, Whiteman M, Spencer JP. Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels. Free Radic Biol Med. 2008 Aug 1;45(3):295-305. Epub 2008 May 5.
Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma. 2004;21(10):1457-1467.