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Pandemic lockdowns linked to sustained cognitive decline among older adults, study finds

8th November 2023

There was a more rapid cognitive decline in people aged over-50 during the pandemic, according to recent research, highlighting the need for public health measures to protect against dementia risk.

Covid-19 infection was found to be a risk factor, but the general more rapid decline in brain health was apparent even if people had not had the virus, the researchers found.

Published in the journal The Lancet Healthy Longevity, the online PROTECT study found a 50% change in the rate of cognitive decline in the first year of the pandemic among the 3,000 participants.

The analysis of tests of short-term memory and complex tasks also found that the rate of cognitive decline was higher in those who already had mild cognitive decline before the pandemic.

It appears to have been exacerbated by a number of factors among the 50-to-90-year-olds taking part, including an increase in loneliness and depression, a decrease in exercise and higher alcohol consumption.

In the second year of the pandemic, reduced exercise continued to affect executive function and associations were sustained between worsening working memory and increased alcohol use. This suggested a sustained impact after the initial 12-month period of lockdowns, the team from the University of Exeter and King’s College London (KCL) said.

The sustained drop in cognition highlights the need for public health interventions to mitigate the risk of dementia – particularly in people with mild cognitive impairment where diagnosis of dementia within five years is a substantial risk, they concluded.

Professor Anne Corbett, professor of dementia research and the PROTECT study lead at the University of Exeter, said: ‘Our findings suggest that lockdowns and other restrictions we experienced during the pandemic have had a real lasting impact on brain health in people aged 50 or over, even after the lockdowns ended.

‘This raises the important question of whether people are at a potentially higher risk of cognitive decline which can lead to dementia.

‘It is now more important than ever to make sure we are supporting people with early cognitive decline, especially because there are things they can do to reduce their risk of dementia later on.’

She added that the findings highlight the need for policymakers to consider the wider health impacts of restrictions like lockdowns when planning future pandemic responses.

Professor Dar Aarsland, professor of old age psychiatry at KCL, said the research adds to the knowledge of the long-standing health consequences of Covid-19, particularly for the most vulnerable people such as older people with mild memory problems.

He said: ‘We know a great deal of the risks for further decline, and now can add Covid-19 to this list. On the positive note, there is evidence that lifestyle changes and improved health management can positively influence mental functioning. The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.’

A version of this article was first published by our sister publication Pulse.

To what extent does eating more nuts help to slow cognitive decline?

27th July 2023

A higher intake of nuts in older adults at risk of cognitive decline could help to slow the decrease in cognitive performance, although the evidence to date is far from clear. Clinical writer Rod Tucker takes a closer look.

The term ‘dementia’ embraces a number of diseases that affect memory, thinking and the ability to perform daily activities. In short, dementia represents the loss of cognitive health, which is key feature of healthy aging.

Unfortunately, the level of dementia appears to be on the rise, becoming a growing and global problem. According to the World Health Organization, there are currently an estimated 55 million people living with dementia worldwide, and this figure is expected to rise in the coming years. Moreover, dementia the seventh leading cause of death and one of the major causes of disability and dependency among older people globally.

There are no known cures for dementia, but efforts have been directed at a range of potential modifiable risk factors, outlined in a 2020 Lancet review. One such factor is diet – particularly the Mediterranean diet, which consists of a high intake of vegetables, legumes, fruits, nuts, cereals and olive oil. But is there evidence to support a higher intake of the individual components in the Mediterranean diet as a means of reducing the risk of cognitive decline?

One constituent that has gained interest in recent years as a strategy to modify cognitive decline, is a higher intake of nuts, but the strength of the evidence supporting this proposition requires more analysis.

Nut intake and cognitive decline

Tree nuts and peanuts (henceforth, nuts) are nutrient-dense foods with a myriad of biologically active ingredients such as unsaturated fatty acids and high-quality vegetable protein, combined with an array of vitamins and beneficial minerals, dietary fibre, phenolic compounds and phytosterols. Peanuts, though botanically classified as legumes rather than nuts, do contain a similar nutrient profile as tree nuts and to all intents and purposes can be considered a nut.

To date, there is compelling evidence for the cardiovascular protective effect of a higher nut intake, largely through an improvement in the lipid profile. For example, it is recognised that a daily intake of small amounts of walnuts lowers LDL cholesterol.

Despite the cardiovascular benefits, much less is known about whether the intake of nuts impacts on brain health, and in particular, if this reduces the risk of cognitive decline. Nevertheless, nuts are likely to have an important effect on the brain as recognised by a recent systematic review on depression.

The review, which included 10 studies with over 60,000 participants, concluded that a higher nut consumption could be associated with a lower risk of depression, fewer depressive symptoms and better mood state in the general population.

In relation to cognitive health, another recent review suggested that while the available evidence was limited and inconclusive, there was likely to be a possible role for nuts for the maintenance of cognitive health and the prevention of cognitive decline, particularly in older adults and those at higher risk.

Randomised trial evidence

With supportive data from observational studies, the real test of efficacy can only really be determined from randomised, interventional, controlled trials. So, how does this evidence stack up?

Unfortunately, findings have been somewhat mixed. For instance, the PREDIMED-NAVARRA randomised trial explored the impact of a Mediterranean diet on cognitive function. Some 522 participants at high vascular risk were assessed and compared a Mediterranean diet supplemented with either extra-virgin olive oil or mixed nuts versus a low-fat control diet. Interestingly, the study found that both Mediterranean diets appeared to improve cognition compared with a low-fat diet.

In contrast, the MedLey Study, which used a Mediterranean diet in older adults compared to a control diet, failed to detect any effect of a Mediterranean diet on cognitive function among healthy older adults. Similarly, a trial in which healthy older adults were randomised to receive an additional intake of almonds found no improvement in cognitive function. A second interventional trial, this time using walnuts, while showing no effect on cognition in healthy elders, did observe that that walnuts might delay cognitive decline in subgroups at higher risk.

The most recent study to examine the effect of consuming nuts on cognitive function, published in June 2023, looked at the two-year impact on cognitive performance in 6,630 adults with a mean age of 65 years who were deemed at risk of cognitive decline.

Nut consumption was categorised as less than one serving per week, one to three servings, between three and seven servings or more than seven serving per week, with a serving defined as 30g. Although the study was prospective in nature, and therefore subject to several recognised limitations, the researchers did see a benefit from increased nut consumption.

Using those who consumed less than one serving of nuts per week as a comparator, the results showed that eating between three and seven servings per week or more than seven portions both demonstrated more favourable changes in general cognitive performance. Although not the main focus of the study, the researchers also found a potential synergistic interaction between nut consumption and depression. In other words, participants with depressive symptoms at baseline tended to benefit more from the consumption of nuts than those without depression.

There seems to be plenty of observational evidence that nut consumption may help to delay the onset of cognitive decline, as randomised interventional studies have not provided consistent findings. In addition, no studies have specifically addressed the effect of eating nuts on hard clinical outcomes such as the development of dementia or Alzheimer’s disease.

While the latest prospective study does suggest a possible cognitive benefit, there is an urgent need for more randomised, interventional trials before recommending increased consumption of nuts to either delay cognitive decline or prevent the onset or progression of cognitive impairment and dementia.

But given a possible link between the cardiovascular and dementia biochemical pathways, it remains plausible that inclusion of more nuts into an individual’s diet might not only improve their cardiovascular health but could help to ameliorate cognitive decline.

Early Alzheimer’s disease cognitive decline slowed by lecanemab

8th December 2022

An RCT has found that the cognitive decline in early Alzheimer’s disease and amyloid burden can be significantly reduced with lecanemab

The cognitive decline present in patients with early Alzheimer’s disease (AD) as well as the amyloid burden are significantly reduced compared to placebo, in those treated with lecanemab according to the results of a randomised, double-blind, phase 3 trial by US researchers.

There are an estimated 55 million across the world living with dementia of whom, approximately 60 to 70% have the most common form, Alzheimer’s disease. Currently available treatments such as cholinesterase inhibitors and memantine, do not alter disease progression but can help with some symptoms. Current thinking the pathophysiology of Alzheimer’s disease is based on the amyloid β-protein (Aβ peptides) theory which purports that in the early stages, there is an imbalance between production and clearance of Aβ peptides and which is a very early, often initiating factor in Alzheimer’s disease (AD). This leads to a build-up of Aβ peptides, and one therapeutic approach gaining interest is the use of monoclonal antibodies directed against amyloid-β (Aβ). In a 2021 systematic review of such antibodies directed against Aβ, there were clinical improvements but with small effect sizes.

In the current study, researchers examined the value of one such monoclonal antibody, lecanemab. Although in a phase 2b proof of concept trial in patients with early Alzheimer’s disease, the drug did not change clinical progression of the disease, it did demonstrate a reduction in brain amyloid accompanied by a consistent reduction of clinical decline in several endpoints. The current study was designed to evaluate the efficacy of lecanemab in patients with early Alzheimer’s disease, i.e., either mild cognitive impairment or mild dementia due to AD and with evidence of amyloid protein as assessed by either PET scan or CSF fluid measurement. Participants were randomised 1:1 to either intravenous lecanemab (10 mg/kg every two weeks) or placebo. The primary endpoint was the change from baseline after 18 months in the Clinical Dementia Rating Sum of Boxes (CDR-SB) which ranges from 0 to 18 and for which higher scores indicate greater cognitive impairment. There were several secondary endpoints, one of which was the change in amyloid burden on PET scanning whereas others assessed changes in cognition.

Early Alzheimer’s disease and change in cognition

A total of 1734 participants with a mean age of 71.2 years (52.3% women) were included and randomised to lecanemab (859) or placebo. The mean baseline CDR-SB score was approximately 3.2 in both groups.

The adjusted mean change from baseline in CDR-SB score was less with lecanemab (1.21) compared to placebo (1.66), i.e., there was less decline in cognition and the mean difference of -0.45 (95% CI -0.67 to -0.23) was statistically significant (p < 0.001).

In a subgroup of 698 participants, the mean amyloid level reduced by -55.48 centiloids in the lecanemab group and by 3.64 in the placebo group (mean difference = -59.12, 95% CI -62.64 to -55.60, p < 0.001).

There were also significant and positive changes favouring lecanemab in the cognition-related outcomes.

The overall incidence of adverse effects was similar between the two groups although lecanemab use resulted in a higher incidence of infusion-related reactions compared to placebo (26.4% vs 7.4%).

The authors concluded that the use of lecanemab reduced markers of amyloid in early Alzheimer’s disease and gave rise to moderately less decline on measures of cognition compared to placebo. They called for longer trials to determine the efficacy and safety of lecanemab in early Alzheimer’s disease.

van Dyck CH et al. Lecanemab in Early Alzheimer’s Disease. N Eng J Med 2022 DOI: 10.1056/NEJMoa2212948

Increased physical activity reduces cognitive decline in older adults with high levels of serum neurofilament light chain

28th March 2022

Increased physical activity in older adults with higher serum neurofilament light chain levels reduces the rate of cognitive decline

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.

Generalised and visceral body fat levels on MRI linked with reduced cognitive scores

11th February 2022

Higher generalised and visceral body fat levels on MRI scans correlate with lower cognitive scores after adjustment for cardiovascular risk

Elevated generalised and visceral body fat levels seen on a magnetic resonance imaging scan have been found to be associated with reduced cognitive scores even after adjustment for cardiovascular risk factors. This was according to a study by researchers from the Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada.

Increased levels of body fat and in particular central adiposity, measured by the waist-to-hip ratio, has been found to have a highly significant association with myocardial infarction risk. The use of magnetic resonance imaging (MRI) enables the detection of visceral fat volume and accumulated evidence shows that visceral adipose tissue is an independent risk marker of cardiovascular and metabolic morbidity and mortality. However, whether elevated levels of both generalised and visceral fat are linked with an impairment of cognitive functioning remain unclear. One prospective study of older adults concluded that abdominal fat in late life appears to confer an increased risk for dementia and cognitive impairment and where body fat levels have been assessed through electrical impedance, visceral fat accumulation was also associated with mild cognitive impairment. In contrast, however, a study in 1047 individuals aged 60 years and older concluded that abdominal obesity might be a protective factor for cognitive function.

With some uncertainty over the relationship between generalised and visceral fat and cognitive function, the Canadian team set out to examine this relationship based on MRI scan results. They turned to data from the Canadian Alliance of Healthy Hearts and Healthy Minds and the Prospective Urban Rural Epidemiological–Mind (PURE-MIND) studies. These studies recruited adults between the ages of 30 and 75 years of age and who had their body fat levels measured by bioelectrical impedance and MRI of the abdomen to measure visceral adipose tissue levels. In addition, all participants underwent MRI of the brain to measure vascular brain injury and cardiovascular risk factors were assessed using lifestyle questionnaires and physical measures. Cognitive assessment was measured using the Digital Symbol Substitution Test (DSST) and the Montreal Cognitive Assessment (MoCA). The DSST scores range from 0 to 133 with lower scores indicative of worse performance. In contrast, the MoCA score ranges from 0 to 30, with higher scores denoting normal cognitive function.

Generalised and visceral body fat levels and cognitive impairment

A total of 9189 adults with a mean age of 57.8 years (56.4% women) were included in the analysis. The women had a higher percentage of body fat compared to men (35.6% vs 25.1%) although men had a higher mean visceral adipose tissue volume (83.6 vs 64.1 ml). The mean DSST score was 72.6 and the MoCA score was 27 and both were slightly higher in women compared to men.

Overall, both a higher total percentage of body fat and visceral adipose score were associated with the lowest DSST score although this was not the case for visceral adipose scores and the MoCA. In regression models fully adjusted for age, sex, educational level and cardiovascular risk factors, the total percentage of body fat remained independently associated with reduced cognitive scores. The authors calculated that for each standard deviation increase in adiposity (9.2% for generalised fat and 36ml of visceral fat), there was a reduction of 0.8 in the DSST score, which was equivalent to 1 year of cognitive ageing. For example, comparing individuals in the highest versus the lowest percentage of body fat, was equivalent to 2.8 years of cognitive ageing. A similar amount of cognitive ageing was also seen between the highest and lowest levels of visceral adipose tissue. However, there were no significant associations between either total body or visceral fat with MoCA scores.

The authors concluded that based on these finding, excess adiposity was a risk factor for reduced cognitive scores and called for strategies to reduce or prevent adiposity as a means of preserving cognitive function in adults.

Anand SS et al. Evaluation of Adiposity and Cognitive Function in Adults JAMA Netw Open 2022