Molly E. McLaren

Brain-Derived Neurotrophic Factor Is Associated with Age-Related Decline in Hippocampal Volume

Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain-derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age, and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood.

Factors Influencing Clinical Correlates of Chronic Traumatic Encephalopathy (CTE): a Review.

Chronic traumatic encephalopathy (CTE) is a neuropathologically defined disease reportedly linked to a history of repetitive brain trauma. As such, retired collision sport athletes are likely at heightened risk for developing CTE. Researchers have described distinct pathological features of CTE as well a wide range of clinical symptom presentations, recently termed traumatic encephalopathy syndrome (TES). These clinical symptoms are highly variable, non-specific to individuals described as having CTE pathology in case reports, and are often associated with many other factors. This review describes the cognitive, emotional, and behavioral changes associated with 1) developmental and demographic factors, 2) neurodevelopmental disorders, 3) normal aging, 4) adjusting to retirement, 5) drug and alcohol abuse, 6) surgeries and anesthesia, and 7) sleep difficulties, as well as the relationship between these factors and risk for developing dementia-related neurodegenerative disease. We discuss why some professional athletes may be particularly susceptible to many of these effects and the importance of choosing appropriate controls groups when designing research protocols. We conclude that these factors should be considered as modifiers predominantly of the clinical outcomes associated with repetitive brain trauma within a broader biopsychosocial framework when interpreting and attributing symptom development, though also note potential effects on neuropathological outcomes. Importantly, this could have significant treatment implications for improving quality of life.

Unique and Interactive Effect of Anxiety and Depressive Symptoms on Cognitive and Brain Function in Young and Older Adults

OBJECTIVE Depression and anxiety and are associated with cognitive deficits and brain changes, especially in older adults. Despite the frequent co-occurrence of these conditions, cognitive neuroscience studies examining comorbid depression and anxiety are limited. The goal of the present study was to examine the unique and combined effect of depressive and anxiety symptoms on cognitive and brain functioning in young and older adults. METHODS Seventy-one healthy, community-dwelling adults between the ages of 18 and 81 were administered a neuropsychological battery and completed the Center for Epidemiologic Studies Depression Scale (CES-D) and the trait form of the State-Trait Anxiety Inventory (STAI-T). A subset of 25 participants also underwent functional magnetic resonance imaging (fMRI) scanning while completing the n-back working memory task. RESULTS Total depressive symptoms, depressed mood symptoms, and somatic symptoms were associated with deficits in speed, working memory and executive functions, especially in older adults. Symptoms of lack of well-being were not associated with any neuropsychological test. Anxiety was associated with better attention and working memory. Moreover, anxiety modified the relationship between depressive symptoms and executive functioning in older adults, as elevated depressive symptoms were associated with worse performance at low levels of anxiety, but not at higher anxiety levels. Similarly, analysis of fMRI data showed that total depressive symptoms and depressed mood symptoms were associated with decreased activity in the superior frontal gyrus at low anxiety levels, but not at high anxiety levels. CONCLUSION Results confirm previous reports that subthreshold depression and anxiety impact cognitive and brain functioning and suggest that the interaction of depression and anxiety results in distinct cognitive and brain changes. Findings highlight the importance of assessing and controlling for symptoms of depression and anxiety in research studies of either condition.

Age Differences in Prefrontal Surface Area and Thickness in Middle Aged to Older Adults

Age is associated with reductions in surface area and cortical thickness, particularly in prefrontal regions. There is also evidence of greater thickness in some regions at older ages. Non-linear age effects in some studies suggest that age may continue to impact brain structure in later decades of life, but relatively few studies have examined the impact of age on brain structure within middle-aged to older adults. We investigated age differences in prefrontal surface area and cortical thickness in healthy adults between the ages of 51 and 81 years. Participants received a structural 3-Tesla magnetic resonance imaging scan. Based on a priori hypotheses, primary analyses focused on surface area and cortical thickness in the dorsolateral prefrontal cortex, anterior cingulate cortex, and orbitofrontal cortex. We also performed exploratory vertex-wise analyses of surface area and cortical thickness across the entire cortex. We found that older age was associated with smaller surface area in the dorsolateral prefrontal and orbitofrontal cortices but greater cortical thickness in the dorsolateral prefrontal and anterior cingulate cortices. Vertex-wise analyses revealed smaller surface area in primarily frontal regions at older ages, but no age effects were found for cortical thickness. Results suggest age is associated with reduced surface area but greater cortical thickness in prefrontal regions during later decades of life, and highlight the differential effects age has on regional surface area and cortical thickness.

Dimensions of depressive symptoms and cingulate volumes in older adults

Clinical depression and subthreshold depressive symptoms in older adults have been linked to structural changes in the cingulate gyrus. The cingulate comprises functionally distinct subregions that may have distinct associations with different types, or symptom dimensions, of depression. This study examined the relationship between symptom dimensions of depression and gray matter volumes in the anterior cingulate, posterior cingulate and isthmus of the cingulate in a nonclinical sample. The study included 41 community-dwelling older adults between the ages of 55 and 81. Participants received a structural magnetic resonance imaging scan and completed the Center for Epidemiologic Studies Depression Scale. Subscale scores for depressed mood, somatic symptoms and lack of positive affect were calculated, and Freesurfer was used to extract cingulate gray matter volumes. Regression analyses were conducted to examine the relationship between depressive symptoms and volumes of cingulate subregions while controlling for sex, age and estimated total intracranial volume. Higher scores on the depressed mood subscale were associated with larger volumes in the left posterior cingulate and smaller volumes in the isthmus cingulate. Higher scores on the somatic symptoms subscale were significantly related to smaller volumes in the posterior cingulate. A trend was observed for a positive relationship between higher scores on the lack of positive affect subscale and larger volumes in the anterior cingulate cortex. These results are consistent with previous findings of altered cingulate volumes with increased depressive symptomatology and suggest specific symptom dimensions of depression may differ in their relationship with subregions of the cingulate.

Depressive symptom severity is associated with increased cortical thickness in older adults.

Structural neuroimaging studies in older adults have consistently shown volume reductions in both major and subthreshold depression. Cortical thickness, another measure of brain structure, has not been well studied in this population. We examined cortical thickness in older adults across a range of depressive symptom (DS) severity.

Transcranial Direct Current Stimulation Use in the Treatment of Neuropsychiatric Disorders: A Brief Review

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has grown in popularity over the past two decades as an alternative treatment option for various neuropsychiatric disorders. tDCS modulates cortical excitability through the application of a weak direct current to the scalp via electrodes placed over cortical regions of interest. It has been shown to be a promising and relatively safe treatment tool with few adverse events. In this article, we will briefly review the efficacy of tDCS in depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder. We will also discuss biomarkers of tDCS efficacy in depression, as it is the most studied neuropsychiatric disorder using tDCS application. We will then offer suggestions for future directions. Although efficacy results show promise, more studies with larger samples and longer treatment periods are needed to better understand the benefits of using tDCS as an alternative treatment option for neuropsychiatric disorders.

Impact of Education on Memory Deficits in Subclinical Depression

Elevated depressive symptoms are associated with cognitive deficits, while higher education protects against cognitive decline. This study was conducted to test if education level moderates the relationship between depressive symptoms and cognitive function. Seventy-three healthy, dementia-free adults aged 18-81 completed neuropsychological tests, as well as depression and anxiety questionnaires. Controlling for age, sex, and state anxiety, we found a significant interaction of depressive symptoms and education for immediate and delayed verbal memory, such that those with a higher education level performed well regardless of depressive symptomatology, whereas those with lower education and high depressive symptoms had worse performance. No effects were found for executive functioning or processing speed. Results suggest that education protects against verbal memory deficits in individuals with elevated depressive symptoms. Further research on cognitive reserve in depression-related cognitive deficits and decline is needed to understand the mechanisms behind this phenomenon.

Vertex-wise examination of depressive symptom dimensions and brain volumes in older adults

Differences in brain volumes have commonly been reported in older adults with both subthreshold and major depression. Few studies have examined the association between specific symptom dimensions of depression and brain volumes. This study used vertex-wise analyses to examine the association between specific symptom dimensions of depression and brain volumes in older adults with subthreshold levels of depressive symptoms. Forty-three community-dwelling adults between the ages of 55 and 81 years underwent a structural Magnetic Resonance Imaging scan and completed the Center for Epidemiologic Studies Depression Scale (CES-D). Vertex-wise analyses were conducted using Freesurfer Imaging Suite to examine the relationship between CES-D subscale scores and gray matter volumes while controlling for sex, age, and education. We found distinct associations between depressed mood, somatic symptoms, and lack of positive affect subscales with regional volumes, including primarily positive relationships in temporal regions and a negative association with the lingual gyrus. The relationship between higher depressed mood subscale scores and larger volumes in the left inferior temporal lobe withstood Monte-Carlo correction for multiple comparisons. Results from this preliminary study highlight the importance of examining depression on a symptom dimension level and identify brain regions that may be important in larger studies of depression.

Effects of body mass index and education on verbal and nonverbal memory

ABSTRACT We previously reported that higher education protects against executive dysfunction related to higher body mass index (BMI) in younger, but not older, adults. We now extend the previous analyses to verbal and nonverbal memory. Fifty-nine healthy, dementia-free community-dwelling adults ranging in age from 18 to 81 years completed the Hopkins Verbal Learning Test – Revised (HVLT-R) and the Brief Visuospatial Memory Test – Revised (BVMT-R). Self-reported years of education served as a proxy for cognitive reserve. We found that more highly educated individuals maintained their BVMT-R immediate recall performance across the range of BMI, but in less educated individuals, higher BMI was associated with worse performance. Our findings suggest that education may play a protective role against BMI-related nonverbal learning deficits, similar to previous reports for verbal memory and executive functioning. Results highlight the importance of considering educational background when determining the risk for BMI-related cognitive impairment in clinical settings.