Tag Archives: Alzheimer’s disease

Air pollution and Alzheimer’s?

16 Sep

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.

 

An Alzheimer’s breakthrough?

2 Sep

This story has received a lot of attention in media. The paper appeared in Nature, perhaps the most prestigious science journal in the world. Here is the abstract:

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.

 

Flaw in the yoga -cognitive impairment study

29 Jul

On Wednesday, I blogged about a new study of the effects of yoga on cognitive impairment. Thinking it over, I realized that some of the study’s results rest on a serious methodological flaw.

The study compares measures before the intervention to measures after the intervention within in each group. For example, it looks at the Geriatric Depression Scale scores for the yoga group before and after the intervention and says that there is a statistically significant difference. But this is not the correct analysis, we want to compare the changes between the yoga group and the control group. An appropriate procedure would have been a gain score analysis. The authors could have subtracted the after treatment scores from the before treatment scores and then compared those two values using an appropriate statistical test.

In the other words, the study had the possibility of comparing the control and the experimental group but failed to so. All it really says it that the scores improved in the treatment group. That is an interesting finding, but it should be considered only exploratory and suggestive. I have no objection to publishing exploratory findings, I have done so myself. But the authors had the opportunity to make a better test and they failed to do so.

Yoga may reduce mild cognitive impairment

27 Jul

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:

BACKGROUND:
No study has explored the effect of yoga on cognitive decline and resting-state functional connectivity.

OBJECTIVES:
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).

METHODS:
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.

RESULTS:
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.

CONCLUSION:
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 [34]), 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.

 

Could THC prevent Alzheimer’s disease?

8 Jul

My gut response to this is that it sounds too good to be true. But one should always keep an open mind.  Here is the description from the Salk Institute press release:

“Salk Institute scientists have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in marijuana can promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer’s disease.

While these exploratory studies were conducted in neurons grown in the laboratory, they may offer insight into the role of inflammation in Alzheimer’s disease and could provide clues to developing novel therapeutics for the disorder.”

You can read the article abstract here.

cynical distrust and dementia

9 Mar

A paper in the journal Neurology reports on a correlation between cynical distrust in old age and dementia.  From the abstract:

“Higher cynical distrust in late life was associated with higher mortality, but this association was explained by socioeconomic position, lifestyle, and health status. Association between cynical distrust and incident dementia became evident when confounders were considered. This novel finding suggests that both psychosocial and lifestyle-related risk factors may be modifiable targets for interventions. We acknowledge the need for larger replication studies.”

As always, note that this is correlational research and does not prove causation.

 

Benzodiazepine not linked to cognitive decline

24 Feb

Here is the paper. The abstract reads:

“Objective To determine whether higher cumulative use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline.

Design Prospective population based cohort.

Setting Integrated healthcare delivery system, Seattle, Washington.

Participants 3434 participants aged ≥65 without dementia at study entry. There were two rounds of recruitment (1994-96 and 2000-03) followed by continuous enrollment beginning in 2004.

Main outcomes measures The cognitive abilities screening instrument (CASI) was administered every two years to screen for dementia and was used to examine cognitive trajectory. Incident dementia and Alzheimer’s disease were determined with standard diagnostic criteria. Benzodiazepine exposure was defined from computerized pharmacy data and consisted of the total standardized daily doses (TSDDs) dispensed over a 10 year period (a rolling window that moved forward in time during follow-up). The most recent year was excluded because of possible use for prodromal symptoms. Multivariable Cox proportional hazard models were used to examine time varying use of benzodiazepine and dementia risk. Analyses of cognitive trajectory used linear regression models with generalized estimating equations.

Results Over a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia, of whom 637 developed Alzheimer’s disease. For dementia, the adjusted hazard ratios associated with cumulative benzodiazepine use compared with non-use were 1.25 (95% confidence interval 1.03 to 1.51) for 1-30 TSDDs; 1.31 (1.00 to 1.71) for 31-120 TSDDs; and 1.07 (0.82 to 1.39) for ≥121 TSDDs. Results were similar for Alzheimer’s disease. Higher benzodiazepine use was not associated with more rapid cognitive decline.

Conclusion The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and dementia.

 

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