Blueberries in the fight against Alzheimer's Disease. What is the evidence?

You may have heard in the popular media that blueberries are a potential panacea for many health conditions including memory and cognitive complaints. Blueberries do indeed seem to be beneficial for ones health however we need to establish the proven limits of these benefits. As this blog focuses on Alzheimer's disease and dementia we will look at the available evidence to determine whether blueberries are worth it in the fight against these diseases.

Unfortunately there is not a lot of human research involving blueberries and either Alzheimer's disease or dementia. There were only two that I could find. In one very small study of 9 elderly adults with early memory changes consumption of blueberry juice daily for 12 weeks improved paired associate learning and word list recall (Krikorian et al, 2010). A much larger epidemiological study of more than 16000 elderly adults found that greater intakes of blueberries was associated with slower rates of cognitive decline (Devore et al, 2012). These studies only support the effects of blueberries for age related cognitive decline and not specifically for Alzheimer's disease or dementia.

There are numerous animal studies that show that supplementation with blueberry extract can prevent or improve cognitive decline in older rats and mice (Malin et al, 2011. Krikorian, Shidler et al, 2010. Andres-Lacueva et al, 2005. Shukitt-Hale et al, 2005). Most of these studies attribute this to the antioxidant effects of the blueberry polyphenols. In a promising study of mice genetically engineered to develop Alzheimer's disease the addition of blueberries to the diet from a young age not only did not develop cognitive deficits seen with the disease but also showed normal levels of Amyloid beta burden into adulthood (Arendash et al, 2003). These effects seen against amyloid beta are supported by two other studies. The first study showed that pretreatment of hippocampal neuronal cells with a blueberry extract reduced the ability of amyloid beta to cause disfunction (Joseph et al, 2007). The second study was conducted in mice and showed that the addition of a blueberries to the diet had a three fold effect of (Zhu et al, 2008):

1. Increasing the clearance of amyloid beta by microglial cells
2. Reducing the aggregation of amyloid beta and hence plaque formations
3. Suppression of pro-inflammatory activity by microglial cell

This is very promising as it demonstrates at least 4 potential mechanisms (including antioxidant properties) by which blueberries could be active against Alzheimer's disease.

This is not however where the potential cognitive benefits blueberries end. There is also preliminary evidence that blueberries may be neuro-protective and enhance plasticity (and hence memory and learning). Three studies in mice examined the effects of blueberry supplementation on specific brain chemicals. All three found that the mice consuming the blueberries had higher levels of brain derived neurotrophic factor (BDNF) (Rendeiro et al, 2013 and 2012. Williams et al, 2008). BDNF is like fertiliser for neurones. It stimulates the growth and formation of new connections which is the basis for learning and memory. Essentially the higher BDNF the faster you learn. In addition to this there are several studies showing that blueberries improve the survivability of neurons. In all of these studies neurons were exposed to a stressor (light, stroke, inflammation). Those neurons exposed to the blueberry extract before the stressor were more likely to survive and be functional than those that were not indicating blueberry's role in protecting from various sources of damage (Tremblay et al, 2013. Galli et al, 2006. Sweeney et al, 2002).

In conclusion blueberries certainly appear to have the ingredients necessary to effectively combat Alzheimer's disease. Most of these effects are only preliminary and have not been studied in human models. It is therefore impossible to say that blueberries would be efective for Alzheimer's patients or even the prevention of such diseases with further extensive studies. That said blueberries are a food item that is safe and also part of a healthy diet. Including them as a in your diet is beneficial on a general health perspective and may have the added benefit of preventing or treating Alzheimer's disease. However for now we can't be certain.

Click on blueberries for cognitive enhancement for more information

1. Blueberry Supplementation Improves Memory in Older Adults (Krikorian et al, 2010)
2. Dietary intakes of berries and flavonoids in relation to cognitive decline (Devore et al, 2012)
3. Short-term blueberry-enriched diet prevents and reverses object recognition memory loss in aging rats (Malin et al, 2011)
4. Blueberry supplementation improves memory in older adults (Krikorian, Shidler et al, 2010)
5. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory (Andres-Lacueva et al, 2005)
6. Dietary supplementation with fruit polyphenolics ameliorates age-related deficits in behavior and neuronal markers of inflammation and oxidative stress (Shukitt-Hale et al, 2005)
7. Blueberry Supplementation Enhances Signaling and Prevents Behavioral Deficits in an Alzheimer Disease Model (Arendash et al, 2003)
8. Dopamine and Aβ-Induced Stress Signaling and Decrements in Ca^{2+} Buffering In Primary Neonatal Hippocampal Cells Are Antagonized by Blueberry Extract (Joseph et al, 2007)
9. Blueberry Opposes β-Amyloid Peptide-Induced Microglial Activation Via Inhibition of p44/42 Mitogen-Activation Protein Kinase (Zhu et al, 2008)
10. Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor (Rendeiro et al, 2013)
11. Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats (Rendeiro et al, 2012)
12. Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels (Williams et al, 2008)
13. Prophylactic neuroprotection by blueberry-enriched diet in a rat model of light-induced retinopathy (Tremblay et al, 2013)
14. Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection (Galli et al, 2006)
15. Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage (Sweeney et al, 2002)