So argues this important piece in Scientific American (sorry, it’s behind a paywall). So far drugs that target Alzheimer’s have been disappointing. Our best evidence suggests that lifestyle interventions (exercise, improvements in diet, and cognitive engagement) really do help.
Don’t get your hopes up yet. The findings reflect animal research, but here is the story from ScienceDaily:
Using LED lights flickering at a specific frequency, researchers have shown that they can significantly reduce the beta amyloid plaques seen in Alzheimer’s disease in the visual cortex of mice. This treatment appears to work by stimulating brain waves known as gamma oscillations, which the researchers discovered help the brain suppress beta amyloid production and invigorate cells responsible for destroying the plaques.
A very surprising finding reported in The New York Times:
Despite fears that rates were going to explode as the population grows older and fatter, and has more, a large nationally representative survey has found the reverse. Dementia is actually on the wane. And when people do get dementia, they get it at older and older ages.
You can read the original study here. The key points:
Question Has the prevalence of dementia among older adults in the United States changed between 2000 and 2012?
Findings In this observational cohort study of more than 21 000 US adults 65 years or older from the nationally representative Health and Retirement Study, dementia prevalence declined significantly, from 11.6% in 2000 to 8.8% in 2012.
Meaning Population brain health seemed to improve between 2000 and 2012; increasing educational attainment and better control of cardiovascular risk factors may have contributed to the improvement, but the full set of social, behavioral, and medical factors contributing to the improvement is still uncertain.
What are the causes of this good news?:
Increases in the level of education among the later-born cohort accounted for some of the decreased dementia risk, and there was some evidence that improvements in treatments for cardiovascular risk factors (eg, diabetes) may also have played a role. However, the full set of social, behavioral, and medical factors contributing to the decline in dementia prevalence is still uncertain.
A paper published in PNAS titled “Magnetite pollution nanoparticles in the human brain,” makes the argument:
We identify the abundant presence in the human brain of magnetite nanoparticles that match precisely the high-temperature magnetite nanospheres, formed by combustion and/or friction-derived heating, which are prolific in urban, airborne particulate matter (PM). Because many of the airborne magnetite pollution particles are <200 nm in diameter, they can enter the brain directly through the olfactory nerve and by crossing the damaged olfactory unit. This discovery is important because nanoscale magnetite can respond to external magnetic fields, and is toxic to the brain, being implicated in production of damaging reactive oxygen species (ROS). Because enhanced ROS production is causally linked to neurodegenerative diseases such as Alzheimer’s disease, exposure to such airborne PM-derived magnetite nanoparticles might need to be examined as a possible hazard to human health.
It’s hard not the find the idea of pollution induced magnetite nanospheres in your brain disturbing. The paper reports:
The specific presence of magnetite in the brain is important because it has been causally linked with potential cellular responses to external magnetic fields
suggesting that the nanoparticles in conjunction with magnetic fields may be a factor. This may explain some of the inconsistent findings on the effects of magnetic fields on humans.
Alzheimer’s disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against Aβ to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aβ, and reduce soluble and insoluble Aβ in a dose-dependent manner. In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner. This is accompanied by a slowing of clinical decline measured by Clinical Dementia Rating—Sum of Boxes and Mini Mental State Examination scores. The main safety and tolerability findings are amyloid-related imaging abnormalities. These results justify further development of aducanumab for the treatment of AD. Should the slowing of clinical decline be confirmed in ongoing phase 3 clinical trials, it would provide compelling support for the amyloid hypothesis.
These are truly exciting results. The paper reports that a “dose-dependent slowing of clinical progression on the Mini Mental State Examination (MMSE) with aducanumab treatment was also observed.” In other words, the larger the dose the slower the cognitive decline. You can find details about Aducanumab here.
The idea that Alzheimer’s disease might be a kind of diabetes has been floating around the research community for a number of years. Now it’s beginning to garner some media attention. Here is a 2008 paper that explains the hypothesis:
‘For nearly three decades of relatively intense research on AD, the inability to interlink this constellation of abnormalities under a single primary pathogenic mechanism resulted in the emergence and propagation of various heavily debated theories, each of which focused on how one particular component of AD could trigger a cascade that contributes to the development of all other known abnormalities. However, reevaluation of the older literature revealed that impairments in cerebral glucose utilization and energy metabolism represent very early abnormalities that precede or accompany the initial stages of cognitive impairment1 and led us to the concept that impaired insulin signaling has an important role in the pathogenesis of AD and the proposal that AD represents “type 3 diabetes.”’
This suggests that the behaviors that protect against diabetes may also protect Alzheimer’s disease.
Let me state my biases right upfront, I am a yoga practitioner, so I may have a tendency to be less critical of yoga positive research. With that in mind, let me report on this study published in The Journal of Alzheimer’s Disease: “Changes in Neural Connectivity and Memory Following a Yoga Intervention for Older Adults: A Pilot Study.” Here is the abstract:
No study has explored the effect of yoga on cognitive decline and resting-state functional connectivity.
This study explored the relationship between performance on memory tests and resting-state functional connectivity before and after a yoga intervention versus active control for subjects with mild cognitive impairment (MCI).
Participants ( ≥ 55 y) with MCI were randomized to receive a yoga intervention or active “gold-standard” control (i.e., memory enhancement training (MET)) for 12 weeks. Resting-state functional magnetic resonance imaging was used to map correlations between brain networks and memory performance changes over time. Default mode networks (DMN), language and superior parietal networks were chosen as networks of interest to analyze the association with changes in verbal and visuospatial memory performance.
Fourteen yoga and 11 MET participants completed the study. The yoga group demonstrated a statistically significant improvement in depression and visuospatial memory. We observed improved verbal memory performance correlated with increased connectivity between the DMN and frontal medial cortex, pregenual anterior cingulate cortex, right middle frontal cortex, posterior cingulate cortex, and left lateral occipital cortex. Improved verbal memory performance positively correlated with increased connectivity between the language processing network and the left inferior frontal gyrus. Improved visuospatial memory performance correlated inversely with connectivity between the superior parietal network and the medial parietal cortex.
Yoga may be as effective as MET in improving functional connectivity in relation to verbal memory performance. These findings should be confirmed in larger prospective studies.
Interesting, but I do have a few concerns. The improvement in depression for the yoga group was statistically significant but the effect size was small:
the yoga group improved significantly in depression (GDS) and in visuospatial memory (Rey-O delayed recall). The clinical improvement in GDS for the yoga group was only minimal (baseline 7.5 (5.1) and follow up 3.9 (2.5); p = 0.01).
If you look at the table you will see that the control group also experience a reduction in depression, the fact that it did not achieve significant is likely an artifact of the study’s small sample size. Moreover, the yoga group started out with much higher depression scores suggesting that the groups might not have been comparable.
Here is the authors’ descriptions of the study’s limitations:
The sample size was only powered towards rs-fMRI findings, and exploring relationships between memory and functional connectivity, not exploring multi-domain effects on cognition. Additionally, we do not have long-term follow-up, which means we are unable to explore cognitive decline towards dementia. Also, it is possible that the enhanced cognitive benefits and connectivity changes resulting from the KK yogic intervention were due to the 60 min of instruction per week, the 12 min per day of Kirtan kriya meditation (shown to positively affect blood flow in the brain ), or a combination of these factors. However, as previous studies only using KK meditation found activation patterns that are in-line with those from the present research, it is unlikely that the weekly classes presented a large deviation. Nevertheless, this is a fruitful area for future research studies, which may aim to parse out the effects of these various activities, or perhaps determine that for optimal benefits weekly classes in addition to a daily meditative practice is recommended.