Over the last 30 years, the longevity of Indians, on average, has shot up remarkably. It was 41 years in the year 1960 and has risen to 68 years of age in 2015. While people live longer, age-related problems — both physical and mental — have become important issues to worry about and find solutions to. Progressive loss of memory and reduction in cognitive ability, together clubbed as dementia, has risen. It has been estimated that 4 million Indians suffer from some form of dementia. While Alzheimer’s disease is one such neural disorder (1.6 millions of the 4 million), there are other disorders contributing to dementia too.
As we grow older, our brains change. The neural cells in the hippocampus, the part associated with learning, acquiring and maintaining memory, are damaged. If one were to find means of protecting this part of the brain and find ways to regenerate these neural cells, it should be possible to overcome and win over this problem and regain cognitive normalcy.
What are the factors leading to dementia? Some studies across the world had suggested that a ‘risk gene’ called APOE4, and another one termed presenilin might play some role here. But the frequency of APOE4 (and presenilin) is too low to be of major consequence (data from Dr. G. Chandak from CCMB Hyderabad and Dr. Mathuranath from Thiruvananthapuram), though there appears to be a regional variation across India (data from Dr. P.P. Singh of Punjabi University, Patiala).
A more important finding, and likely causative factor, comes from the imaging of the brain; this has found the hippocampus and some other parts of the brain to be tangled a bit, with some insoluble sheet-like ‘plaques’ which interfere with signal transmission in the brain. (Such a thing was first detected in what was called as the ‘mad cow’ disease detected in cows in U.K. which were fed meat products to eat). Yet others have suggested the role of a protein called brain-derived neurotropic factor or BDNF; when its level falls below optimum, dementia results.
Several methods have been tried to address the dementia problem. Attempts using vaccine candidates have not been successful, not attempts to use immune-therapy. Remarkably, sustained physical exercise seems to help — a remarkable connection between the physical and the mental. Exercise has long been thought of to stimulate neurogenesis, namely the generation of new nerve cells, just as it does muscular and cardiac cells. Towards this, a group led by Dr. Rudolph E. Tanzi at Harvard University in Cambridge, MA, USA has published a note in the September 7, 2018 issue the journal Science, using a mouse afflicted with Alzheimer’s disease as the model.
How exercise helps
This group based its argument on the fact that the hippocampus in the brain contains neuro-progenitor cells which continue to generate new neurons. This well-known process is called Adult Hippocampal Neurogenesis or AHN. In Alzheimer’s and other dementias, this process of making new neurons, namely, AHN, is impaired. The group argued whether AHN can be increased in the Alzheimer mouse by pushing the rodent to exercise on a running wheel for 3 hours every day for several days. (Why exercise? The reason behind this has been the claim that exercise is helpful for the body and the brain). They found several positive effects. (1) AHN was increased; more nerve cells were seen to be made; (2) the ‘plaques’ in the brain of the animal were reduced; (3) the levels of the molecule BDNF went up and (4) there was some improvement in memory. Thus, exercise in the demented mouse reduces pathology, increases neurons in the hippocampus and improves memory.
‘Bottling exercise with chemicals’ ?
The next question was: if exercise increases AHN through a rise in the BDNF levels and reduces pathology, why not replace exercise itself, and substitute it instead with biochemical treatment? To this end, they used methods to increase the levels of BDNF by injecting a drug molecule called AICAR (5-amino imidazole-4-carboxamide riboside), and another molecule called P7C3, which helps in the survival of new neurons. As Dr. Tara Spires-Jones and Dr. Craig Ritchie comment on the Harvard work in the same issue of Science, this paper provides clues about why exercise is good for memory. (They also add tongue-in-cheek that we could perhaps “bottle” the effects of exercise through vials of AICAR and P7C3! This may be appealing to those who cannot do physical exercise, and for the lazy ones, who do not want to!) Note, too, that the mouse was on the running wheel 3 hours per day for several days; in other words exercise should be sustained and continuous. Moral: It is thus a good idea for senior citizens to start and continue exercise early enough, say from their forties onwards. It is good for the overall body and the brain.
Does meditation help?
One issue that neither the Harvard paper nor its commentary makes any mention of is on the claim that meditation improves cognition, and is good against neuro-degenerative diseases. A paper by Dr Marciniak and others in Frontiers in Behavioural Neurosciences, 2014, (see the link https://doi.org/10.3389/fnbeh.2014.00017) has reviewed several studies relating to the meditation — cognitive improvement connection, and conclude that meditation could be a potentially suitable non-pharmacological intervention aimed at the prevention of cognitive decline in the elderly. However, given the limitations due to methods and differences in the various types of meditation used (Buddhist, Zen, Vihangya Yoga, Kirtan Kriya and others), they conclude that further research in this direction could help verify the validity of the findings and clarify the problematic aspects. Here again, sustained long- term meditation appears important and not a one-off type. Here is a set of experiments that some Indian neurosciences laboratories can work on, in order to obtain some molecular and cellular insights on the issue.
dbala@lvpei.org
