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13th August 2021
Tau is a microtubule-associated protein in neurons but aberrant assembly of the protein is present in neurodegenerative disorders. However, while abnormalities in the assembly of tau appear to be strongly associated with the development of disorders such as dementia and Alzheimer’s disease, it remains unclear how this links with upstream events. Tau levels can now be measured in blood and higher levels have been associated with cognitive decline and with the development of Alzheimer’s disease. Increased physical exercise improves blood flow to the brain and greater levels of activity appear to be associated with a reduced risk of developing degenerative conditions such as Alzheimer’s disease. Given that tau levels can serve as a biomarker of cognitive decline what remains uncertain is whether it is possible to correlate changes cognition with preventative strategies such as physical exercise over time. This was the aim of a study by a team from the Rush Institute for Healthy Aging, Rush University, Chicago, US. They used data contained within the Chicago Health and Aging Project (CHAP), which is a population-based cohort of African Americans and White participants, 65 years and older. The CHAP study is designed to explore chronic common health problems, especially risk factors for incident Alzheimer’s disease.
For the present study, the researchers included participants older than 65 years and without Alzheimer’s disease at baseline. Samples of tau were measured between 1994 and 2012 and frozen and later assayed. The team collected information on the levels of physical activity of participants and categorised this as either low, medium and high. Medium activity was where it was for less than 150 minutes per week, or high, if greater than 150 minutes. Low levels indicated that participants did not undertake any physical activity. Tau blood levels were also measured and considered as either high (> 0.40 pg/ml) or low (<0.40 pg/ml) based on earlier data suggesting a higher rate of cognitive decline in those with levels greater than 0.40. The main outcome of the study was global cognitive function based on a battery of tests and the measurement duration for the study was 18 years.
A total of 1159 participants were included with a mean age of 77.4 years (63% female) and with 60% of African American descent. In participants with a high tau level (> 0.40 pg/ml) and a medium level of physical activity, there was a 58% slower rate of cognitive decline per year compared to those undertaking little physical activity. Similarly, in those with high tau levels and high physical activity, the rate of cognitive decline was 41% slower than those with low activity. Even where tau levels were low, medium physical activity was associated with a 2% slower rate of decline and a 27% lower rate for those with high physical activity.
The authors concluded that physical activity was associated with a much slower decline in cognitive function among those with both low and high tau levels and that this could be easily measured with tau levels. They called for future studies to examine the relationship between tau levels and other forms (i.e., strength training) of physical activity.
Desai P et al. Longitudinal Association of Total Tau Concentrations and Physical Activity with Cognitive Decline in a Population Sample. JAMA Netw Open 2021
23rd October 2020
Patients with type 2 diabetes have also been shown to have an increased the risk of cognitive impairment and dementia. Achievement of good glycaemic control is associated with a reduction in the risk of many of adverse health outcomes and this can be attained through weight loss, but the evidence for an improvement in cognitive impairment is currently mixed. In this study, researchers from several centres in the US have reported on the results from the Action for Health in Diabetes (look AHEAD) study which suggests that it is glycaemic control, rather than weight reduction, which has the greatest impact on cognitive functioning. The look AHEAD study is a single blind, randomised trial that recruited 5145 individuals during 2001 to 2004 with a BMI >25kg/m2, a HbA1c < 11%, triglycerides < 600mg/dl and a systolic/diastolic blood pressure < 160/100 mmHg. Participants were randomised to either an intensive lifestyle intervention (ILI) or a diabetes support and education (DSE) control group and the interventions continued until 2012, which was an average of 9.9 years. For the cognitive assessment arm, 1089 participants from the original study were recruited at year 8 or 9 of follow-up and undertook 2 or 3 cognitive assessments, that evaluated verbal learning, memory, speed of processing, executive function and global cognitive functioning.
There was an equal number of participants from the ILI and DSE groups; the mean age of both samples was 58 years, and 42% of both groups was male and roughly 10% had pre-existing cardiovascular disease. Improvements in blood sugar control was associated with greater improvements in cognitive scores for most measures. In contrast, the association between improvements in weight loss and cognitive scores was less clear and depended to some extent, on the cognitive measure.
The authors were unable to account for these findings and concluded that any improvements in cognitive function were largely dependent on baseline levels of adiposity and cardiovascular disease history.
Carmichael OT et al. Long-term change in physiological markers and cognitive performance in type 2 diabetes: the look AHEAD trial. J Clin Endrocrinol Metab 2020; doi:10.1210/clinem/dgaa591