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28th March 2022
Increased physical activity levels in older adults with high serum levels of neurofilament light chain (NFL) leads to a reduction in the rate of cognitive decline. This was the conclusion of a study by researchers from the Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, US.
Neurofilament light chain is a neuronal cytoplasmic protein expressed in large calibre myelinated axons. Furthermore, in both central nervous system and peripheral nervous system diseases associated with axonal injury or degeneration, the concentration of NFL has been found to increase in both cerebrospinal fluid (CSF) and blood. In addition, levels of CSF NFL are associated with cognitive impairments in patients with Alzheimer disease and fronto-temporal dementia. As a result, it has been suggested that NFL could be used to predict the development of sporadic Alzheimer’s disease and cognitive decline. One factor which appears to be associated with a reduced cognitive decline is physical activity and in a 2011 meta-analysis, the authors concluded that there was a significant and consistent protection for all levels of physical activity against the occurrence of cognitive decline.
For the present study, the US team wanted to examine whether among individuals with high NFL concentrations, increased physical activity was associated with a slowed rate of cognitive decline over time. They turned to the Chicago Health and Aging Project (CHAP), which is a longitudinal population study of common chronic health problems of older persons and in particular, risk factors for incident Alzheimer’s disease. Blood samples were taken and the concentration of NFL measured at baseline and during each follow-up appointment and dichotomised as low (< 25.5 pg./ml) or high (> 25 pg./ml). Levels of physical activity were self-reported divided into three groups: little activity, medium and high, in which the latter group reported physical activity levels > 150 minutes/week. A number of cognitive tests were used to assess global cognitive function. The main outcome measure was the association of baseline activity and NFL concentrations with changes in global cognitive function over time.
Increased physical activity and NFL in relation to cognitive decline
A total of 1158 participants with a mean age of 77.4 years (63% female) were included in the study. The mean level of physical activity per week was 170.78 minutes and the geometric mean NFL concentration was 26.1 pg/ml.
Among those with a high NFL levels, indicating more axonal injury, individuals engaging in medium physical activity (< 150 minutes/week), had a 12% slower rate of global cognitive decline compared to those in the low physical activity group. Similarly, those with increased physical activity (i.e., the high group), had a 36% slower rate of decline in comparison to the low physical activity group.
Interestingly, the the rates of cognitive decline were also higher among those with lower levels of NFL, i.e., with less neural damage. For example, in comparison to the group who undertook little or no physical activity, those who undertook medium physical activity had a 43% slower decline and the high activity group, at 30% slower decline.
The authors concluded that among older adults with high levels of serum NFL, increased physical activity levels were associated with a slower rate of cognitive decline. They added that future studies should examine the relationship between cognitive decline and different forms of exercise such as aerobics and strength training.
Desai P et al. Examination of Neurofilament Light Chain Serum Concentrations, Physical Activity, and Cognitive Decline in Older Adults JAMA Netw Open 2022
7th March 2022
Neurofilament light is the best biomarker for the assessment of brain injury in patients who experience hypoxic ischaemic brain injury (HIBI) after the return of spontaneous circulation following a cardiac arrest. This was main finding of a systematic review and meta-analysis by a team from the Division of Critical Care Medicine, Vancouver General Hospital, Vancouver, Canada.
Hypoxic-ischaemic brain injury, represents a recognised consequence of cardiac arrest. For example, in one study examining the cause of death after an out-of-hospital cardiac arrest, it was found that neurological injury was responsible for two-thirds of all deaths. In fact, HIBI after cardiac arrest is a leading cause of mortality and long-term neurologic disability in survivors. Moreover, patients with HIBI are at a high risk for secondary brain injury from, for example, brain oedema, tissue ischaemia and haematoma expansion. Biomarkers can be used to identify those at risk through the provision of prognostic information and two such marker, neuron specific enolase (NSE) and S-100B are released following injury to neurons and glial cells, respectively and their blood values are presumed to correlate with the extent of HIBI following a cardiac arrest. Others include neurofilament light (which reflects white matter damage) and tau although the relative prognostic value of these biomarkers has not been evaluated.
For the present analysis, the Canadian team searched electronic databases for studies using biomarkers including neuron specific enolase, S100 beta, S100 calcium binding protein, tau and neurofilament light. They included only those for which at least one of the biomarkers was used to prognosticate the neurological outcome for patients with HIBI after a cardiac arrest. The team calculated the summary receiver operating characteristic curve (SROC) for each biomarker at 48 hours after the cardiac arrest and used this as the primary outcome measure. Subgroup analysis was performed comparing with targeted temperature management (TTM), which is a recognised method designed to minimise post-anoxic injury and improving neurological outcome after cardiac arrest.
Neurofilament light and predictive value for neurological outcomes
A total of 86 studies with 10, 567 patients and a mean age of 62.8 years (73.6% male) were included in the final analysis.
In terms of the SROC, neurofilament light had the highest area under the curve (AUC) for predictive value of unfavourable neurological outcomes, with a value of 0.92 (95% CI 0.84 – 0.97), followed by tau with an AUC of 0.89 (95% CI 0.71 – 0.97). This was higher than neuron-specific enolase (AUC = 0.84) and S100 calcium (AUC = 0.85).
When compared with TTM, SROC curves were calculated for each biomarker and the results did not differ appreciably and neurofilament light still had the highest AUC (0.92, 95% CI 0.86 – 0.95).
The authors concluded that neurofilament light which is a biomarker for white matter damage, was associated with the highest accuracy to predict unfavourable neurological outcomes in those with HIBI after a cardiac arrest.
Hoiland RL et al. Neurologic Prognostication After Cardiac Arrest Using Brain Biomarkers: A Systematic Review and Meta-analysis. JAMA Neurol 2022