Tag: cognitive impairment

Categories : Mental Health NeurologyTags :

Neuroscientists Identify a New Subtype of Depression that Resists SSRIs

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In a new study, scientists at Stanford Medicine have described a new category of depression, the cognitive biotype, which accounts for 27% of depressed patients and is not effectively treated by commonly prescribed antidepressants. The findings were reported in JAMA Network.

For these patients, cognitive tasks showed difficulty in planning ahead, self-control, sustaining focus despite distractions and suppressing inappropriate behaviour; imaging showed decreased activity in two brain regions responsible for those tasks.

Because depression has traditionally been defined as a mood disorder, doctors commonly prescribe selective serotonin reuptake inhibitors (SSRIs), but these are less effective for patients with cognitive dysfunction. Researchers said that targeting these cognitive dysfunctions with less commonly used antidepressants or other treatments may alleviate symptoms and help restore social and occupational abilities.

The study is part of a broader effort by neuroscientists to find treatments that target depression biotypes, according to the study’s senior author, Leanne Williams, PhD, professor of psychiatry and behavioural sciences.

“One of the big challenges is to find a new way to address what is currently a trial-and-error process so that more people can get better sooner,” Williams said. “Bringing in these objective cognitive measures like imaging will make sure we’re not using the same treatment on every patient.”

Finding the biotype

In the study, 1008 adults with previously unmedicated major depressive disorder were randomly given one of three widely prescribed typical antidepressants: escitalopram (Lexapro) or sertraline (Zoloft), which act on serotonin, or venlafaxine-XR (Effexor), which acts on both serotonin and norepinephrine. Seven hundred and twelve of the participants completed the eight-week regimen.

Before and after treatment with the antidepressants, the participants’ depressive symptoms were measured using two surveys – one, clinician-administered, and the other, a self-assessment, which included questions related to changes in sleep and eating. Measures on social and occupational functioning, as well as quality of life, were tracked as well.

The participants also completed a series of cognitive tests, before and after treatment, measuring verbal memory, working memory, decision speed and sustained attention, among other tasks.

Before treatment, scientists scanned 96 of the participants using functional magnetic resonance imaging as they engaged in a task called the “GoNoGo” that requires participants to press a button as quickly as possible when they see “Go” in green and to not press when they see “NoGo” in red. The fMRI tracked neuronal activity by measuring changes in blood oxygen levels, which showed levels of activity in different brain regions corresponding to Go or NoGo responses. Researchers then compared the participants’ images with those of individuals without depression.

The researchers found that 27% of the participants had more prominent symptoms of cognitive slowing and insomnia, impaired cognitive function on behavioural tests, as well as reduced activity in certain frontal brain regions – a profile they labelled the ‘cognitive biotype’.

“This study is crucial because psychiatrists have few measurement tools for depression to help make treatment decisions,” said Laura Hack, MD, PhD, the lead author of the study and an assistant professor of psychiatry and behavioural sciences. “It’s mostly making observations and self-report measures. Imaging while performing cognitive tasks is rather novel in depression treatment studies.”

Pre-treatment fMRI showed those with the cognitive biotype had significantly reduced activity in the dorsolateral prefrontal cortex and dorsal anterior cingulate regions during the GoNoGo task compared with the activity levels in participants who did not have the cognitive biotype. Together, the two regions form the cognitive control circuit, which is responsible for limiting unwanted or irrelevant thoughts and responses and improving goal selection, among other tasks.

After treatment, the researchers found that for the three antidepressants administered, the overall remission rates were 38.8% for participants with the newly discovered biotype and 47.7% for those without it. This difference was most prominent for sertraline, for which the remission rates were 35.9% and 50% for those with the biotype and those without, respectively.

“Depression presents in different ways in different people, but finding commonalities – like similar profiles of brain function – helps medical professionals effectively treat participants by individualising care,” Williams said.

Depression isn’t one size fits all

Williams and Hack propose that behaviour measurement and imaging could help diagnose depression biotypes and lead to better treatment. A patient could complete a survey on their own computer or in the doctor’s office, and if they are found to display a certain biotype, they might be referred to imaging for confirmation before undergoing treatment.

Researchers under Williams and Hack are studying another drug, guanfacine, that specifically targets the dorsolateral prefrontal cortex region. They believe this treatment could be more effective for patients with the cognitive subtype.

Williams and Hack hope to conduct studies with participants who have the cognitive biotype, comparing different types of medication with treatments such as transcranial magnetic stimulation (TMS) and cognitive behavioural therapy.

“I regularly witness the suffering, the loss of hope and the increase in suicidality that occurs when people are going through our trial-and-error process,” Hack said. “And it’s because we start with medications that have the same mechanism of action for everyone with depression, even though depression is quite heterogeneous. I think this study could help change that.”

Source: Stanford Medicine

Categories : AddictionTags :

Alcohol Detox Programme Participants Show Rapid Return to Normal Cognition

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Source: Pixabay CC0

Sixty-three percent of participants who had severe alcohol use disorder who went through a detoxification programme saw improvement within the first ten days, according to the results of a French study. The findings were published in Alcohol and Alcoholism.

Impaired cognition is known to have an impact on the efficacy of substance use rehabilitation programmes, but substance use, such as alcohol, is known to have in impact on cognition. Therefore, in order to better tailor treatment programmes, it is important to know how quickly normal cognitive levels can be restored.

To assess recovery of alcohol-related neuropsychological deficits in a group of patients with pure severe alcohol use disorder (AUD) during a detoxification program using the Brief Evaluation of Alcohol-Related Neuropsychological Impairment (BEARNI) test.

Thirty-two patients admitted to French hospitals with severe AUD using DSM-IV criteria (24 men, mean age = 45.5 ± 6.8 years old) were assessed using the BEARNI 8 ± 2 days after alcohol cessation (T1) and then were reassessed within 18 ± 2 days after alcohol cessation (T2). The primary study endpoint was the number of patients initially impaired at T1 who recovered cognitive functions at T2 assessment.

At T1, 59% (n = 19) patients with pure severe AUD had at least one impaired cognitive function assessed by the BEARNI. At T2, 63% of the patients with AUD with deficits at T1 had normal BEARNI cognitive scores. Among the subtests, the highest percentage of participants with normal subtest scores were 100% in the verbal fluency category, 67% in visuospatial, 63% in the memory category and 60% in alphabetical span.

The researchers also noted that those participants in the present study who recovered within 18 days of abstinence, did so earlier than reported in previous studies.

“Additional studies assessing cognitive improvements during abstinence, and especially earlier in abstinence, are needed,” the authors concluded. “Further studies should also assess the early course of social cognition, attentional bias and inhibition deficits in patient with alcohol use disorder early in abstinence, given their clinical impact.”

Categories : Ageing NeurologyTags :

Memory Loss and Confusion More Common among Middle-aged Smokers

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Middle-aged smokers are much more likely to report having memory loss and confusion than nonsmokers, and the likelihood of cognitive decline is lower for those who have quit, even recently, according to a new study appearing in the Journal of Alzheimer’s Disease.

The study is the first to examine the relationship between smoking and cognitive decline using a one-question self-assessment asking people if they’ve experienced worsening or more frequent memory loss and/or confusion.

The findings build on previous research that established relationships between smoking and Alzheimer’s Disease and other forms of dementia, and could point to an opportunity to identify signs of trouble earlier in life, said Jenna Rajczyk, lead author of the study.

It’s also one more piece of evidence that quitting smoking is good not just for respiratory and cardiovascular reasons, but to preserve neurological health, said Rajczyk, a PhD student in Ohio State’s College of Public Health, and senior author Jeffrey Wing, assistant professor of epidemiology.

“The association we saw was most significant in the 45–59 age group, suggesting that quitting at that stage of life may have a benefit for cognitive health,” Wing said. A similar difference wasn’t found in the oldest group in the study, which could mean that quitting earlier affords people greater benefits, he said.

Researchers used data from the 2019 Behavioral Risk Factor Surveillance System Survey to compare subjective cognitive decline (SCD) measures for current smokers, recent former smokers, and those who had quit years earlier. The analysis included 136 018 people 45 and older, and about 11% reported SCD.

The prevalence of SCD among smokers in the study was almost 1.9 times that of nonsmokers. The prevalence among those who had quit less than 10 years ago was 1.5 times that of nonsmokers. Those who quit more than a decade before the survey had an SCD prevalence just slightly above the nonsmoking group.

“These findings could imply that the time since smoking cessation does matter, and may be linked to cognitive outcomes,” Rajczyk said.

The simplicity of SCD, a relatively new measure, could lend itself to wider applications, she said.

“This is a simple assessment that could be easily done routinely, and at younger ages than we typically start to see cognitive declines that rise to the level of a diagnosis of Alzheimer’s Disease or dementia,” Rajczyk said. “It’s not an intensive battery of questions. It’s more a personal reflection of your cognitive status to determine if you’re feeling like you’re not as sharp as you once were.”

Many people don’t have access to more in-depth screenings, or to specialists, making the potential applications for measuring SCD even greater, she said.

Wing said it’s important to note that these self-reported experiences don’t amount to a diagnosis, nor do they confirm independently that a person is experiencing decline out of the normal ageing process. But, he said, they could be a low-cost, simple tool to consider employing more broadly.

Source: Ohio State University

Categories : CancerTags :

A Clue to Breast Cancer Survivors’ Cognitive Problems

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Woman receiving mammogram
Source: National Cancer Institute

Why breast cancer survivors experience troubling cognitive problems is a long-standing mystery, and for which inflammation is one possible culprit. A new long-term study of older breast cancer survivors published in the Journal of Clinical Oncology adds evidence to this link.

Higher levels of the inflammatory marker C-reactive protein (CRP) were related to older breast cancer survivors reporting cognitive problems in the new study.

“Blood tests for CRP are used routinely in the clinic to determine risk of heart disease. Our study suggests this common test for inflammation might also be an indicator of risk for cognitive problems reported by breast cancer survivors,” said study lead author Judith Carroll, an associate professor at UCLA. 

The Thinking and Living with Cancer (TLC) Study is one of the first long-term efforts to examine the potential link between chronic inflammation and cognition in breast cancer survivors 60 and older, who make up a majority of the nearly 4 million breast cancer survivors in the United States. Previous research has focused largely on younger women and women immediately after therapy, making it difficult to draw conclusions about CRP’s role in long-term cognitive problems among older breast cancer survivors.   

In TLC, teams of researchers from around the country talked to, and obtained blood samples from, hundreds of breast cancer survivors and women without cancer up to six times over the course of five years. The study was motivated by hearing from survivors and advocates that cognitive problems are one of their major worries. 

“Cognitive issues affect women’s daily lives years after completing treatment, and their reports of their own ability to complete tasks and remember things was the strongest indicator of problems in this study,” said co-senior study author Dr Jeanne Mandelblatt, a professor of oncology at Georgetown University who is the lead of the TLC study.   

“Being able to test for levels of inflammation at the same time that cognition was being rigorously evaluated gave the TLC team a potential window into the biology underlying cognitive concerns,” said Elizabeth C. Breen, a professor emerita of psychiatry and biobehavioral sciences at the Cousins Center for Psychoneuroimmunology at UCLA, who also served as co-senior study author. 

The women’s cognition was evaluated through a commonly used questionnaire. The study found higher CRP levels among survivors were predictive of lower reported cognitive function among breast cancer survivors. There was no similar relationship between CRP levels and reported cognition in the women without cancer. 

Cognitive performance, as measured by standardised neuropsychological tests, failed to show a link between CRP and cognition. The authors say this may indicate women are more sensitive to differences in their everyday cognitive function, self-reporting changes that other tests miss.

The authors said their study supports the need for research on whether interventions that can lower inflammation – including increased physical activity, better sleep, and anti-inflammatory medications – may prevent or reduce cognitive concerns in older breast cancer survivors. 

Source: EurekAlert!

Categories : COVIDTags :

Long COVID Cognitive Impairment More Widespread than Thought

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Scientists following COVID patients up to 12 months after diagnosis have found that mild cognitive impairment is common even after mild to moderate COVID. The study results, currently in preprint on the medRxiv server awaiting peer review, suggest that cognitive impairment, though barely noticeable, may affect large portions of the global population.

The finding comes as the US Centers for Disease Control reported that up to 1 in 5 Americans experienced at least one symptom that could be attributable to Long COVID.

SARS-CoV-2 is believed to cause lasting cognitive impairment in some cases, though the exact nature of it was not clear. Severe COVID cases risk damage through hypoxia, stroke, as well as the immune and inflammatory response to SARS-CoV-2. Mild to moderate COVID cases are still at risk of brain dysfunction, and cognitive deficits, providing a window into the potential mechanisms of brain injury without the confounding role of severe disease and its complications. Given the large numbers of people who had mild to moderate COVID disease, there would be significant implications for public health.

To assess the effects of the disease, the researchers studied 128 SARS-CoV-2 positive patients, assessing cognition and olfaction at set intervals after COVID diagnosis, along with lung capacity and blood biomarkers including the kynurenine pathway (KP).

After correcting for demographics, mild to moderate cognitive impairment was present in 26% on year post diagnosis, respectively. Overall cognitive performance declined mildly, but was statistically significant. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly associated with cognitive decline.

“The immune system reacts first with the virus … tries to basically get rid of the virus,” she said to ABC News. “Then it goes a little bit into overdrive and this overdrive does not fully calm down.”

The KP pathway was seen to be disturbed similarly to the way inflammation is caused by viruses such as HIV.

“I think we’re seeing something a bit akin here, where this low level of inflammation is more and more understood as being able to traffic to the brain, or even being within the brain and affecting those regions of the brain where we process information that demand speed, extra attention and extra cognitive demands,” she explained.

Dr Cysique emphasises that the cognitive decline recorded among most participants in the study is mild and they may not even notice it.

The researchers suggested that as a unique biomarker, the KP offers a potential therapeutic target for COVID-related cognitive impairment.

Categories : NeurologyTags :

Body Fat Linked to Risk of Reduced Cognitive Function

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Photo by Andres Ayrton from Pexels

A new study published in JAMA Network Open has found that greater body fat is a risk factor for reduced cognitive function, such as processing speed, in adults.

Even when accounting for cardiovascular risk factors or vascular brain injury, the association between body fat and lower cognitive scores persisted. This suggests other, currently unknown, mechanisms linking excess body fat to reduced cognitive function.

For the study, 9166 participants were measured by bioelectrical impedance analysis to assess their total body fat. In addition, 6733 underwent magnetic resonance imaging (MRI) to measure abdominal fat packed around the organs known as visceral fat, and the MRI measured vascular brain injury, including silent brain infarctions and high white matter hyperintensities. Cardiovascular risk factors were measured using health and lifestyle questions and physical measures, and cognitive assessment was measured by the Digital Symbol Substitution Test and the Montreal Cognitive Assessment.

Lead author Sonia Anand, lead author, professor of medicine of McMaster University said: “Our results suggest that strategies to prevent or reduce having too much body fat may preserve cognitive function.”

She added that “the effect of increased body fat persisted even after adjusting for its effect on increasing cardiovascular risk factors like diabetes and high blood pressure, as well as vascular brain injury, which should prompt researchers to investigate which other pathways may link excess fat to reduced cognitive function.”

Co-author Eric Smith, associate professor of clinical neurosciences at the University of Calgary, said that “preserving cognitive function is one of the best ways to prevent dementia in old age. This study suggests that one of the ways that good nutrition and physical activity prevent dementia may be by maintaining a healthy weight and body fat percentage.”

Participants had no existing cardiovascular diseases, and ranged in age from 30 to 75, with an average age of about 58 and 56% were women. Most were White European origin, with about 16% other ethnic backgrounds. 

Source: McMaster University

Categories : Environmental EffectsTags :

Ozone Linked to Cognitive Impairment with Age

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A robust link has been established between long-term ozone exposure and an increased risk of cognitive impairment in older adults, according to a large-scale study published in Environment International.

Air pollution has long been considered a major risk factor for an ageing society. Fine airborne particulate matter can lead to dementia and other cognitive disabilities. But beyond airborne particles, little is known about the way in which other pollutants can pose a similar danger.

The researchers chose to focus on ambient ozone, a highly reactive gas that exists in much of smog at ground level. They then observed health outcomes in nearly 10 000 older adults across China and analysed the extent to which long-term ozone exposure may have impacted their cognitive ability over time.

The results, they found, were startling. For every 10 microgram increase of yearly average ozone exposure, the risk for cognitive impairment grew by more than 10%. Through their analysis, the researchers also found that this association held even when they abstracted away individual risk factors such as smoking, drinking and education level. That is, older adults in China who were exposed to high levels of yearly ozone pollution were more likely to develop cognitive disabilities later in life, no matter what other activities they were involved in.

“Our findings suggest potential benefits in delaying the progression of cognitive decline among older adults if ozone levels are reduced below the new WHO Global Air Quality Guideline for ozone pollution,” said Kai Chen, Ph.D., assistant professor at the Yale School of Public Health and the study’s lead author.

The researchers acknowledged limitations such as observational data being unable to establish a causal link. More research is needed into ozone’s destructive mechanism. And since many older adults in China spend more time indoors, their ozone exposure may be different.

Nonetheless, the findings match what other researchers have found in areas across the globe: Over the past several years, studies have traced a similar link in adults in the United States and in Taiwan, and have also found an association between ozone exposure and other neurological diseases.

The study shows that ozone exposure needs to be curbed worldwide to prevent healthcare systems from being overwhelmed as populations age and pollution increases.

Study co-author Professor Robert Dubrow said what makes this issue more urgent is that “ozone pollution is projected to be worsening under climate change.” Reducing this threat could bring significant benefits to public health and improve quality of life.

Source: Yale University

Categories : NeurologyTags :

Impairment Lasts up to 10 Hours After Cannabis

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A comprehensive analysis of 80 scientific studies has identified a ‘window of impairment’ of between three and 10 hours caused by moderate to high doses of tetrahydrocannabinol (THC), the cannabis component that causes intoxication. According to the researchers, these results have consequences for drug-driving laws around the world.

How long the impairment lasts depends on the THC dose, whether it is taken orally or inhaled, on the usage habits of the cannabis user and the demands of the task. The psychoactive THC component of cannabis has potential medical applications in treating nausea, sleep apnoea, fibromyalgia and chronic pain, though these applications are controversial and currently difficult to study due to legal issues, though off-label use is common. 
Previous research by Dr Arkell and colleagues has shown that cannabidiol (CBD), one of the medically active components of cannabis, does not cause impairment in driving. CBD has analgesic and anti-inflammatory actions, as well as anxiolytic, antiemetic, antipsychotic, and neuroprotective antioxidant properties

Medical and non-medical legal cannabis use is on the rise worldwide.
THC causes acute impairment in driving and cognitive performance, but there is uncertainty among users about the duration of this impairment and when they can start tasks such as driving after consuming cannabis.
“Our analysis indicates that impairment may last up to 10 hours if high doses of THC are consumed orally,”  said lead author Dr Danielle McCartney, Lambert Initiative for Cannabinoid Therapeutics at the University of Sydney. “A more typical duration of impairment, however, is four hours, when lower doses of THC are consumed via smoking or vaporization and simpler tasks are undertaken (eg, those using cognitive skills such as reaction time, sustained attention and working memory). This impairment may extend up to six or seven hours if higher doses of THC are inhaled and complex tasks, such as driving, are assessed.”

A moderate THC dose is considered about 10 milligrams in this study, but could be higher for a regular user, said the researchers.

Co-author Dr Thomas Arkell, also from the Lambert Initiative, said: “We found that impairment is much more predictable in occasional cannabis users than regular cannabis users. Heavy users show significant tolerance to the effects of cannabis on driving and cognitive function, while typically displaying some impairment.”

Regular cannabis users might consume more to get the same effect, resulting in equivalent impairment, the authors noted.

In the case of oral use as in medical cannabis drops, tablets etc, the impairment takes longer to manifest and has a longer duration than the inhalation route.

The findings have implications for so-called drug-driving laws, the researchers said.

Professor Iain McGregor, Academic Director of the Lambert Initiative, said: “THC can be detected in the body weeks after cannabis consumption while it is clear that impairment lasts for a much shorter period of time. Our legal frameworks probably need to catch up with that and, as with alcohol, focus on the interval when users are more of a risk to themselves and others. Prosecution solely on the basis of the presence of THC in blood or saliva is manifestly unjust.

“Laws should be about safety on the roads, not arbitrary punishment. Given that cannabis is legal in an increasing number of jurisdictions, we need an evidence-based approach to drug-driving laws,” Prof McGregor said.

Source: News-Medical.Net

Journal information: McCartney, D., et al. (2021) Determining the magnitude and duration of acute Δ9-tetrahydrocannabinol (Δ9-THC)-induced driving and cognitive impairment: A systematic and meta-analytic review. Neuroscience & Biobehavioral Reviews. doi.org/10.1016/j.neubiorev.2021.01.003.