Below you will find a list of publications on work that has been supported by CCNA. Each title is linked to its PubMed listing and abstract or, if the article is open-access, to the article itself. For those articles that are believed to be of particular interest to the general public, a lay abstract is provided.

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This research from Montero-Odasso and colleagues investigated how speed of walking while performing a demanding cognitive task can predict whether a patient with Mild Cognitive Impairment (MCI) might later develop dementia. MCI, a condition where individuals present with small changes in their memory and mental functions, is often a precursor to dementia, though not everyone who has MCI goes onto develop dementia. Montero-Odasso and colleagues followed 112 older adults over six years who presented with MCI. Every two years, the participants were asked to first walk normally for six meters without doing a simultaneous task (single-task), and then to walk while simultaneously doing a secondary task that requires thinking and attention, such as counting backwards by one, by seven, or while naming animals (dual-task). In all tasks, the participants’ walking speed was measured. Over six years, 24% of the initial sample of older adults with MCI (27/112) developed dementia. The researchers found that the mean normal (single-task) walking speed of these 27 older adults was equivalent to the normal walking speed of the 85 older adults who did not develop dementia. In contrast, the older adults who eventually developed dementia were slower than those that did not develop dementia when they were walking while simultaneously doing a secondary task (e.g. counting backwards, or naming animals). In fact, the risk of progressing to dementia was two to three times greater in older adults with MCI whose walking speed diminished by at least 20 percent (e.g. slowing from one meter per second to 0.8 meters per second) in the dual-task walking condition relative to the single-task walking condition. The results of this study suggest that a significant slowing down in walking speed while doing a cognitively demanding task relative to normal walking speed (without doing a cognitively demanding task) can be used by clinicians to detect older adults with MCI who are at risk of developing dementia.

Badhwar A, Tam A, Dansereau C, Orban P, Hoffstaedter F, Bellec P. Resting-state network dysfunction in Alzheimer's disease: A systematic review and meta-analysis. Alzheimer's & dementia : diagnosis, assessment & disease monitoring. 2017;8:73-85

2017

This CCNA-funded study suggests that, while lactic acid production is beneficial for memory in the healthy aging brain, it might be detrimental in Alzheimer’s disease (AD). These findings will help guide the development of drugs to alter lactic acid metabolism for the treatment of AD. Specifically, this article demonstrates that lactic acid (a metabolite), and the enzymes that generate it, decrease with age in the brains of normal mice. Although an increase of lactic acid-producing enzymes is correlated with improved memory in older mice, when it comes to an Alzheimer’s disease mouse model, elevated levels are – surprisingly – associated with poorer memory.  

This meta-analysis is the first of its kind to study sex differences in driving cessation among individuals with and without dementia.

Drs. Mary Tierney, Mark Rapoport, Gary Naglie, and Ms. Nicolette Baines found that driving cessation is significantly more prevalent in women with dementia than men. What’s more, the same pattern was found in men and women without dementia. 

Their review highlights the need for more research on the reasons for the observed sex differences, which may be due to biological sex differences as well as gender differences in roles and relationships between men and women. Longitudinal studies are also needed in order to estimate the incidence of sex differences in driving cessation in participants who have undergone diagnostic assessments to both include and exclude dementia. These longitudinal studies should also compare driving cessation in regions with different population densities and transportation options, the researchers explain.

Above all, their findings show that sex and gender differences may have important implications for supportive responses offered to drivers with dementia both prior to and following driving cessation.

A relatively new concept, “Cognitive-Frailty” describes the overlapping presence of two syndromes that can occur with aging: cognitive impairment and physical frailty, which is characterized by weakness, decreased energy, and reduced activity. It has been suggested that having cognitive-frailty makes one more likely to develop dementia than frailty alone. Dr. Montero-Odasso and colleagues tested this hypothesis, and also examined whether a combination of cognitive impairment (defined as a total score below 26/30 on the Montreal Cognitive Assessment (MoCA)) and a slow walking speed (defined as walking slower than 1 meter per second) was a predictor of developing dementia.

What they found was that people with frailty were more likely to have cognitive impairment than people without frailty, but cognitive-frailty did not lead to dementia more often than frailty alone. Those with cognitive impairment and slow walking speed, however, were the most likely to develop dementia. This suggests that a simple motor test, such as one’s walking speed, and a reliable cognitive test, such as the MoCA, are superior to the cognitive-frailty construct for detecting individuals at risk for dementia.

 

In many neurodegenerative diseases – including Alzheimer's disease – deposits of misfolded proteins form in the brain. While visible through a microscope, these deposits are too small to be isolated and extracted. In this article, researchers show how their new technique – spatially targeted microproteomics (STOMP) – makes use of tightly-focused laser light to attach chemical handles to these protein deposits, so that they can be recovered for identification and analysis. Through using STOMP, researchers have identified a number of proteins not previously associated with pathology in Alzheimer’s disease (including some proteins involved in signalling across synapses between neurons), and hope to see STOMP used to explore the underlying biology of other neurodegenerative diseases.

This article describes a study design that aims to prove that the combination of two drugs – acting on the two major pathophysiological mechanisms of Alzheimer’s disease (i.e. amyloid deposition and tau hyperphosphorylation) - can modify the disease’s progression. We suggest that these drugs would work best in delaying progression to dementia in persons with mild cognitive impairment that is due to Alzheimer's disease. Furthermore we propose that if such a drug combination is effective, it could be affordable using the models of drug combinations against tuberculosis, AIDS/HIV and breast cancer. This article, written by a first year medical student at McGill University, is an example of the importance of exposing physicians in training to the social impact of clinical research. This is the first publication of the Ethical, Legal, Social Impact (ELSI) committee of the Canadian Consortium on Neurodegeneration in Aging (CCNA).