Advancements in the field of mental health continue to emerge, making it challenging for clinicians to stay up to date with the latest findings. This article highlights recent developments in our understanding of risk factors associated with certain brain disorders.

CONCUSSION MAY NOT AFFECT IQ IN CHILDREN

Intellectual functioning is typically measured by an intelligence quotient (IQ) score. It can be predictive of multiple factors such as academic success and quality of life.^[1] The test requires expert administration and interpretation.^[2] The impact of concussion on IQ in children is yet to be determined. Furthermore, it is not known whether the type of injury and the role of external factors such as socioeconomic background influence a child’s IQ following concussion. A new, multicenter study aimed to compare IQ scores in children with concussion, also termed mild traumatic brain injury, with children who had orthopedic injury.^[1]

In the study, which included almost 900 children with concussion or orthopedic injury, differences between groups in full-scale IQ (Cohen's d = 0.13) and matrix reasoning scores (d = 0.16) were small. Children's IQ scores were not significantly different in the first months after concussion compared with before concussion.

"We draw the inference that IQ scores are unchanged, in the sense that they're not different from [those of] kids with other types of injuries that don't involve the brain," study author Keith Owen Yeates, PhD, Ronald and Irene Ward Chair in Pediatric Brain Injury and a professor of psychology at the University of Calgary, told Medscape Medical News.

The study was published July 17 in Pediatrics.^[1]

A Representative Sample

The investigators analyzed data from 2 prospective cohort studies of children who were treated for concussion or mild orthopedic injury at 2 hospitals in the United States and 5 in Canada. Participants were aged 8 to 17 years and were recruited within 24 hours of the index event. Patients in the US completed IQ and performance validity testing at 3 to 18 days after injury. Patients in Canada did so at 3 months after injury. The study used the short-form IQ test. The investigators included 866 children in their analysis.

Using linear modeling, Bayesian analysis, and multigroup factor analysis, the researchers found "very small group differences" in full-scale IQ scores between the 2 groups. Mean IQ was 104.95 for the concussion group and 106.08 for the orthopedic-injury group. Matrix reasoning scores were 52.28 and 53.81 for the concussion and orthopedic-injury groups, respectively. Vocabulary scores did not differ between the 2 groups (53.25 for the concussion group and 53.27 for the orthopedic-injury group).

The study population is "pretty representative" from a demographic perspective, although it was predominantly White, said Yeates. "On the other hand, we did look at socioeconomic status, and that didn't seem to alter the findings at all," he added. The sample size is one of the study's strengths, said Yeates. "Having 866 kids is far larger, I think, than just about any other study out there." Drawing from 7 children's hospitals in North America is another strength, he said. "Previous studies, in addition to having smaller samples, were from a single site and often recruited from a clinic population, not a representative group for a general population of kids with concussion."

The findings must be interpreted precisely, however. "We don't have actual preinjury data, so the more precise way of describing the findings is to say they're not different from kids who are very similar to them demographically, have the same risk factors for injuries, and had a similar experience of a traumatic injury," said Yeates. "The IQ scores for both groups are smack dab in the average range."

Overall, the results are encouraging. "There's been a lot of bad news in the media and in the science about concussion that worries patients, so it's nice to be able to provide a little bit of balance," said Yeates. "The message I give parents is that most kids recover within 2-4 weeks, and we're much better now at predicting who's going to [recover] and who isn't, and that helps, too, so that we can focus our intervention on kids who are most at risk."

Some children will have persisting symptoms, but evidence-based treatments are lacking. "I think that'll be a really important direction for the future," said Yeates.

Graduated Return

Commenting on the findings for Medscape Medical News, Michael Esser, MD, a pediatric neurologist at Alberta Children's Hospital and an associate professor in pediatrics at the University of Calgary, said that they can help allay parents' concerns about concussions. "It can also be of help for clinicians who want to have evidence to reassure families and promote a graduated return to activities," he said. "In particular, the study would support the philosophy of a graduated return to school or work, after a brief period of rest, following concussion." Esser did not participate in the study.

The research is also noteworthy because it acknowledges that the differences in the design and methodology used in prior studies may explain the apparent disagreement over how concussion may influence cognitive function.

"This is an important message," said Esser. "Families struggle with determining the merit of a lot of information due to the myriad of social media comments about concussion and the risk for cognitive impairment. Therefore, it is important that conclusions with a significant implication are evaluated with a variety of approaches."

SOCIAL ISOLATION LINKED TO LOWER BRAIN VOLUME

In the United States, loneliness and social isolation in older individuals is considered a major public health risk and has been associated with increased risk for dementia and other diseases. Nearly a quarter of people aged ≥ 65 years are thought to be socially isolated.^[3] Indeed, research has also shown that a low rate of social interaction with other people is associated with risk for depression in later life.^[4] In a recent study, researchers aimed to determine the relationship between low frequency of social contact and brain volume among Japanese people without dementia aged ≥ 65 years. They also assessed how depressive symptoms feed into this association.

In the study, social isolation in older individuals was linked to reduced brain volume in regions associated with memory. Furthermore, the association between social isolation and reduced brain volume appeared to be at least partly mediated by depressive symptoms.

"We believe that efforts should be made to reduce social isolation among the elderly as much as possible," investigator Toshiharu Ninomiya, MD, PhD, professor of epidemiology and public health at Kyushu University in Fukuoka, Japan, told Medscape Medical News. The study was published online July 12 in Neurology.^[4]

A Dementia Prevention Strategy

Ninomiya noted there have been several studies suggesting that social interaction is beneficial in preventing cognitive decline and the onset of dementia. In addition, recent epidemiological studies have shown social isolation is associated with a risk for cognitive decline and dementia.^[5]

Although the investigators note that very little is known about the link between the two, some studies have shown that social isolation is linked with depressive symptoms in older adults, and late-life depression has been associated with brain atrophy.^[6]

To explore the potential link between social isolation and brain atrophy, as well as the role of depression as a potential mediator, the investigators studied nearly 9000 citizens aged 65 and older as part of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD),^[7] an ongoing, community-based nationwide cohort study of dementia in Japan.

Participants were recruited from 8 research sites across Japan, and each had a baseline magnetic resonance imaging (MRI) scan between 2016 and 2018. The investigators excluded those with a dementia diagnosis at baseline. Self-reported frequency of social contact was categorized as every day, several times a week, several times a month, or seldom.

Participants also answered questions about medical history and treatment, antihypertensive or antidiabetic medications, exercise, current alcohol intake, and smoking habits. Depressive symptoms were assessed with the Geriatric Depression Scale. Of the participants, 57% were women, and the mean age was 73 years.

Lower Brain Volume

Total brain volume was lower in those with the lowest frequency of social contact vs those with the highest frequency (67.3% vs. 67.8%). Less social contact was also linked to smaller temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala volumes. White matter lesion volume increased with fewer social interactions, from 0.26% in the most social group to 0.30% in the least. Cognitive function was higher in participants who had daily social contact compared with those who had the least contact (28 vs 27 on the Mini-Mental State Examination; P < .001). Scores between 25 and 30 are considered normal.

Depressive symptoms were lower in the daily-contact group compared with the seldom-contact group (P < .001). The team also found that lower frequency of social contact was significantly associated with the smaller superior, middle, or inferior temporal gyrus; and a smaller fusiform gyrus, transverse temporal gyrus, temporal pole, and entorhinal cortex, among other subregions. Mediation analyses indicated that depressive symptoms only accounted for 15% to 29% of the associations of lower frequency of social contact with each regional volume.

Worse Physical Health

The results also showed that socially isolated participants were more likely to have diabetes, hypertension, were more likely to smoke, and to be physically inactive. "Cardiovascular risk factors have been reported to cause endothelial dysfunction in the brain, which could in turn lead to problems in maintaining microcirculation and blood–brain barrier function," the investigators write.

Some epidemiological studies have associated cardiovascular risk factors with brain atrophy, they noted, which could have been one of the underlying mechanisms. Another possibility is that reduced cognitive stimulation due to social isolation may cause brain atrophy, they add. "Ultimately," Ninomiya said, "The detailed mechanism of the relationship between social isolation and brain volume is not yet clear." He also said more research is needed to know whether the findings would apply to people in other countries.

In an accompanying editorial,^[8] Alexa Walter, PhD, and Danielle Sandsmark, MD, PhD, from the University of Pennsylvania, Philadelphia, note that isolation has been associated with many adverse health outcomes, including increased risk of heart disease, stroke, and premature death. "Given these findings, future work considering social health factors in the context of neurological disease is an important area of research to consider. Additionally, leveraging other existing longitudinal studies could provide us with an opportunity to better understand these relationships within populations and inform public policy to address these issues," Walter and Sandsmark write.

FLUCTUATING CHOLESTEROL, TRIGLYCERIDES TIED TO INCREASED DEMENTIA RISK

Alzheimer's disease (AD) accounts for 60% to 70% of the 55 million cases of dementia globally.^[9] As such, a clear understanding of its risk factor and effective prevention strategies are needed.^[10] Previous studies have shown a link between high cholesterol levels and increased dementia risk, but such research has usually been based on a single measurement, the researchers note. Only a few studies have examined variability of cholesterol levels over time, but they have also shown a link between varying levels and dementia risk. How the risk differs among specific types of cholesterol is not yet fully known. To explore this question, investigators analyzed medical records in the Rochester Epidemiology Program, a medical records-linkage system in southern Minnesota and western Wisconsin in a new study.^[10]

Fluctuating cholesterol and triglyceride levels in older adults were associated with a greater risk of AD and Alzheimer's-related dementia (ADRD). Participants with the greatest variability in total cholesterol levels had a 19% increased risk for AD or ADRD within 12 years of baseline than those with stable levels. In addition, those with the highest variability in triglycerides had a 23% increased risk. The study did not differentiate between dementia types.

The findings were published online July 5 in Neurology.

Unclear Mechanism

Participants were excluded from the study if they had a prior diagnosis of AD/ADRD or did not have 3 or more lipid measurements within the baseline data collection period, leaving a final cohort of 11,571 participants. All participants were aged 60 or older. The mean age of the sample was 71, and 54% were female. Investigators recorded participants' total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) on at least 3 different days in the 5 years before the start of the study in January 2006.

The investigators then followed the cohort from baseline until incident AD/ADRD, death, or December 31, 2018, whichever came first. Participants were divided into groups depending on the degree of variation in lipid measurements, with the lowest group having the least variation over time and the highest group having the most variation over time.

Over a mean follow-up of 10 years, 2470 (21%) of the participants developed AD/ADRD. After adjusting for variables that could affect the risk for dementia, including sex, race, education, BMI, and lipid-lowering treatments, investigators found that participants who had the most variation in total cholesterol levels had a 19% increased risk of AD/ADRD (95% CI: 1.04, 1.36, P = .011). Those with the highest variability in triglycerides had a 23% increased risk of AD/ADRD (95% CI: 1.08, 1.41, P = .002).

No associations were found with lipid-lowering medication history, and variability in levels of LDL-C and HDL-C independently were not associated with later AD/ADRD. The mechanism contributing to increased variation in lipids and subsequent dementia remains unclear but one possible explanation involves endothelial dysfunction, the researchers note. "Increased levels of serum markers related to endothelial dysfunction have also been shown to increase the risk of cognitive impairment and lower cerebral blood flow, which may increase the risk of incident AD/ADRD in later life," they write. They add that further research is needed to pinpoint the underlying mechanism.

One of the study's limitations was that it did not differentiate between dementia subtypes in participants. In addition, researchers did not gather data on apolipoprotein (APOE) haplotypes, noting that their effect on lipid profiles and dementia risk could "further impact lipid variabilities' association with AD/ADRD."

Healthy Heart, Healthy Brain

Commenting on the study for Medscape Medical News, Christopher Weber, PhD, Alzheimer's Association Director of Global Science Initiatives, noted the strong relationship between heart health and brain health.

"Cholesterol fluctuations can negatively impact the brain's vascular health and increase the risk of developing cognitive decline and dementia, including Alzheimer's disease."

He added that "endothelial dysfunction is discussed in this article, which is an early marker of atherosclerosis and could contribute to the connection between cholesterol fluctuations and Alzheimer's. This could negatively affect cerebral blood flow and increase the risk of cognitive impairment and Alzheimer's in later life."

Weber said that maintaining a low and stable level of cholesterol — particularly total cholesterol and triglycerides — may be beneficial for reducing the risk for Alzheimer's and other dementia types.

This transcript has been edited for style and clarity.

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