Effect of Metabolic Syndrome Risk Factors on Processing Speed and Executive Function in Three Racialized Groups.

BACKGROUND: Metabolic syndrome (MetS) has been associated with increased risk for Alzheimer's disease and related dementias (ADRD). Understanding the association of MetS risk factors to processing speed and executive function in the pre-clinical stages of ADRD in under-represented groups would offer insight on potential mechanisms through which MetS associates with ADRD risk. OBJECTIVE: Examine association of MetS features and processing speed and executive function across three racial groups. METHODS: Cognitively unimpaired adults from the Wisconsin Alzheimer's Disease Research Center and the Wisconsin Registry for Alzheimer's Disease Prevention completed blood-draws and neuropsychological testing. Six cognitive outcomes were assessed in association to MetS risk factors: Trailmaking Tests A and B, Animal Fluency, Digit Symbol, and composite scores for Processing Speed and Executive Function. Linear mixed effect models were used to assess the relationship between MetS risk factor count and longitudinal cognitive performance across three racialized groups. RESULTS: Participant sample sizes varied by outcome analyzed (N = 714-1,088). African American and Native American groups exhibited higher rates of MetS than non-Hispanic Whites. MetS was associated with processing speed and executive function across all racialized groups. Three-way interaction by racialized group was limited to one cognitive outcome: Trailmaking Test A. CONCLUSION: Metabolic dysfunction incrementally affects cognitive trajectory, with generally similar associations across racial groups. Since racialized groups exhibit higher levels of both MetS and ADRD, MetS may represent a driving factor for increased ADRD risk experience by racialized group and an important and modifiable target through which to reduce risk of ADRD.

Increased risk for falling associated with subtle cognitive impairment: secondary analysis of a randomized clinical trial.

BACKGROUND/AIMS: Having dementia increases patients' risk for accidental falls. However, it is unknown if having mild cognitive deficits also elevates a person's risk for falls. This study sought to clarify the relationship between subtle cognitive impairment, measured with a widely-used, clinic-based assessment, the Mini Mental State Exam (MMSE), and risk for falls. METHODS: In a secondary analysis of the Kenosha County Falls Prevention Study, a randomized controlled trial targeting older adults at risk for falls, we examined the association between baseline MMSE and prospective rate of falls over 12 months in 172 subjects randomized to control group. RESULTS: Using univariate analysis, the rate of falls increased with each unit decrease in MMSE score down to at least 22 (rate ratio 1.25, 95% confidence interval (CI) 1.09-1.45, p = 0.0026). Using stepwise multivariate regression, controlling for ability to perform activities of daily living, use of assistive device, current exercise, and arthritis, the association between MMSE score and falls rate persisted (rate ratio 1.20, 95% CI 1.03-1.40, p = 0.021). CONCLUSION: Minimal decrements on the MMSE were associated with elevations in rate of falls, suggesting that subtle cognitive deficits reflected in MMSE scores above a cut-off consistent with a diagnosis of dementia, can influence risk for falls.

An Examination of Brain Abnormalities and Mobility in Individuals with Mild Cognitive Impairment and Alzheimer's Disease.

Background: Mobility changes are concerning for elderly patients with cognitive decline. Given frail older individuals' vulnerability to injury, it is critical to identify contributors to limited mobility. Objective: To examine whether structural brain abnormalities, including reduced gray matter volume and white matter hyperintensities, would be associated with limited mobility among individuals with cognitive impairment, and to determine whether cognitive impairment would mediate this relationship. Methods: Thirty-four elderly individuals with mild cognitive impairment (MCI) and Alzheimer's disease underwent neuropsychological evaluation, mobility assessment, and structural brain neuroimaging. Linear regression was conducted with predictors including gray matter volume in six regions of interest (ROI) and white matter hyperintensity (WMH) burden, with mobility measures as outcomes. Results: Lower gray matter volume in caudate nucleus was associated with slower speed on a functional mobility task. Higher cerebellar volume was also associated with slower functional mobility. White matter hyperintensity burden was not significantly associated with mobility. Conclusion: Our findings provide evidence for associations between subcortical gray matter volume and speed on a functional mobility task among cognitively impaired individuals.

Cognitive Effects of Soy Isoflavones in Patients with Alzheimer's Disease.

BACKGROUND: In a previous trial, treatment with soy isoflavones was associated with improved nonverbal memory, construction abilities, verbal fluency, and speeded dexterity compared to treatment with placebo in cognitively healthy older adults. OBJECTIVE: The current trial aimed to examine the potential cognitive benefits of soy isoflavones in patients with Alzheimer's disease. METHODS: Sixty-five men and women over the age of 60 were treated with 100 mg/day soy isoflavones, or matching placebo capsules for six months. APOE genotype was determined for all participants. Cognitive outcomes and plasma isoflavone levels were measured at baseline, and at two additional time points: three and six months after baseline. RESULTS: Of the sixty-five participants enrolled, thirty-four (52.3% ) were women, and 31 (47.7% ) were APOEɛ4 positive. Average age was 76.3 (SD = 7.2) years. Fifty-nine (90.8% ) subjects completed all study visits. Plasma isoflavone levels increased in subjects treated with soy isoflavones compared to baseline and to placebo, although intersubject variability in plasma levels was large. No significant differences in treatment effects for cognition emerged between treatment groups or genders. Exploratory analyses of associations between changes in cognition and plasma isoflavone levels revealed an association between equol levels, and speeded dexterity and verbal fluency. CONCLUSIONS: Six months of 100 mg/day treatment with soy isoflavones did not benefit cognition in older men and women with Alzheimer's disease. However, our results suggest the need to examine the role of isoflavone metabolism, i.e., the ability to effectively metabolize soy isoflavones by converting daidzen to equol when attempting to fully clarify the cognitive effects of isoflavones.

Disruption of caudate working memory activation in chronic blast-related traumatic brain injury.

Mild to moderate traumatic brain injury (TBI) due to blast exposure is frequently diagnosed in veterans returning from the wars in Iraq and Afghanistan. However, it is unclear whether neural damage resulting from blast TBI differs from that found in TBI due to blunt-force trauma (e.g., falls and motor vehicle crashes). Little is also known about the effects of blast TBI on neural networks, particularly over the long term. Because impairment in working memory has been linked to blunt-force TBI, the present functional magnetic resonance imaging (fMRI) study sought to investigate whether brain activation in response to a working memory task would discriminate blunt-force from blast TBI. Twenty-five veterans (mean age = 29.8 years, standard deviation = 6.01 years, 1 female) who incurred TBI due to blast an average of 4.2 years prior to enrollment and 25 civilians (mean age = 27.4 years, standard deviation = 6.68 years, 4 females) with TBI due to blunt-force trauma performed the Sternberg Item Recognition Task while undergoing fMRI. The task involved encoding 1, 3, or 5 items in working memory. A group of 25 veterans (mean age = 29.9 years, standard deviation = 5.53 years, 0 females) and a group of 25 civilians (mean age = 27.3 years, standard deviation = 5.81 years, 0 females) without history of TBI underwent identical imaging procedures and served as controls. Results indicated that the civilian TBI group and both control groups demonstrated a monotonic relationship between working memory set size and activation in the right caudate during encoding, whereas the blast TBI group did not (p < 0.05, corrected for multiple comparisons using False Discovery Rate). Blast TBI was also associated with worse performance on the Sternberg Item Recognition Task relative to the other groups, although no other group differences were found on neuropsychological measures of episodic memory, inhibition, and general processing speed. These results could not be attributed to caudate atrophy or the presence of PTSD symptoms. Our results point to a specific vulnerability of the caudate to blast injury. Changes in activation during the Sternberg Item Recognition Task, and potentially other tasks that recruit the caudate, may serve as biomarkers for blast TBI.

Declining cognition and falls: role of risky performance of everyday mobility activities.

BACKGROUND: Declining cognition is a risk factor for falls among older adults. The extent to which impaired judgment in performance of daily activities increases fall risk is unclear. OBJECTIVE: The aim of this study was to determine whether engagement in mobility activities in a risky manner explains the association between declining cognition and rate of falls. DESIGN: This study was a secondary analysis of baseline and prospective data from older adults enrolled in the intervention arm of a randomized clinical trial. METHODS: Two hundred forty-five community-dwelling older adults (79% female; mean age=79 years, SD=8.0) who were at risk for falls received physical, cognitive, and functional evaluations. Cognition was assessed with the Short Portable Mental Status Questionnaire (SPMSQ). Using interview and in-home assessment data, physical therapists determined whether participants were at risk for falls when performing mobility-related activities of daily living (ADL) and instrumental ADL (IADL). Falls were measured prospectively for 1 year using monthly falls diaries. RESULTS: Declining cognition was associated with increased number of mobility activities designated as risky (1.5% of mobility activities performed in a risky manner per SPMSQ point) and with increased rate of falls (rate ratio=1.16 for each unit change in SPMSQ score). Risky performance of mobility activities mediated the relationship between cognition and rate of falls. LIMITATIONS: Risk assessment was based on the clinical judgment of experienced physical therapists. Cognition was measured with a relatively insensitive instrument, and only selected mobility activities were evaluated. CONCLUSIONS: Engagement in mobility ADL and IADL tasks in a risky manner emerged as a link between declining cognition and increased number of falls, suggesting a mechanism through which the rate of falls may increase. Specifically, declining cognition is associated with performance of mobility activities in an unsafe manner, thereby increasing the risk for falls.

Performance-based assessment of falls risk in older veterans with executive dysfunction.

Falling is a serious hazard for older veterans that may lead to severe injury, loss of independence, and death. While the American Geriatrics Society (AGS) provides guidelines to screen individuals at risk for falls, the guidelines may be less successful with specific subgroups of patients. In a veteran sample, we examined whether the Timed Up and Go (TUG) test, including a modified version, the TUG-Cognition, effectively detected potential fallers whose risk was associated with cognitive deficits. Specifically, we sought to determine whether TUG tasks and AGS criteria were differentially associated with executive dysfunction, whether the TUG tasks identified potential fallers outside of those recognized by AGS criteria, and whether these tasks distinguished groups of fallers. Participants included 120 mostly male patients referred to the Memory Assessment Clinic because of cognitive impairment. TUG-Cognition scores were strongly associated with executive dysfunction and differed systematically between fallers grouped by number of falls. These findings suggest that the TUG-Cognition shows promise in identifying fallers whose risk is related to or compounded by cognitive impairment. Future research should study the predictive validity of these measures by following patients prospectively.

Neural activation during response inhibition differentiates blast from mechanical causes of mild to moderate traumatic brain injury.

Military personnel involved in Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) commonly experience blast-induced mild to moderate traumatic brain injury (TBI). In this study, we used task-activated functional MRI (fMRI) to determine if blast-related TBI has a differential impact on brain activation in comparison with TBI caused primarily by mechanical forces in civilian settings. Four groups participated: (1) blast-related military TBI (milTBI; n=21); (2) military controls (milCON; n=22); (3) non-blast civilian TBI (civTBI; n=21); and (4) civilian controls (civCON; n=23) with orthopedic injuries. Mild to moderate TBI (MTBI) occurred 1 to 6 years before enrollment. Participants completed the Stop Signal Task (SST), a measure of inhibitory control, while undergoing fMRI. Brain activation was evaluated with 2 (mil, civ)×2 (TBI, CON) analyses of variance, corrected for multiple comparisons. During correct inhibitions, fMRI activation was lower in the TBI than CON subjects in regions commonly associated with inhibitory control and the default mode network. In contrast, inhibitory failures showed significant interaction effects in the bilateral inferior temporal, left superior temporal, caudate, and cerebellar regions. Specifically, the milTBI group demonstrated more activation than the milCON group when failing to inhibit; in contrast, the civTBI group exhibited less activation than the civCON group. Covariance analyses controlling for the effects of education and self-reported psychological symptoms did not alter the brain activation findings. These results indicate that the chronic effects of TBI are associated with abnormal brain activation during successful response inhibition. During failed inhibition, the pattern of activation distinguished military from civilian TBI, suggesting that blast-related TBI has a unique effect on brain function that can be distinguished from TBI resulting from mechanical forces associated with sports or motor vehicle accidents. The implications of these findings for diagnosis and treatment of TBI are discussed.

The identification and assessment of late-life ADHD in memory clinics.

OBJECTIVE: Little data exist about ADHD in late life. While evaluating patients' memory problems, the memory clinic staff has periodically identified ADHD in previously undiagnosed older adults. The authors conducted a survey to assess the extent to which other memory clinics view ADHD as a relevant clinical issue. METHOD: The authors developed and sent a questionnaire to memory clinics in the United States to determine the extent to which they identified patients with ADHD and the extent to which they took it into consideration. RESULTS: Approximately one half of the memory clinics that responded reported seeing ADHD patients, either identifying previously diagnosed cases and/or newly diagnosing ADHD themselves. One fifth of clinics reported screening regularly for ADHD, and few clinics described accessing collateral informants to establish the diagnosis. CONCLUSION: This article suggests that U.S. memory clinics may not adequately identify and address ADHD in the context of late-life cognitive disorders.