Depression, Vascular Burden, and Dementia Prevalence in Late Middle-Aged and Older Black Adults.

OBJECTIVES: Late-life depression and white matter hyperintensities (WMH) have been linked to increased dementia risk. However, there is a dearth of literature examining these relationships in Black adults. We investigated whether depression or WMH volume are associated with a higher likelihood of dementia diagnosis in a sample of late middle-aged to older Black adults, and whether dementia prevalence is highest in individuals with both depression and higher WMH volume. METHODS: Secondary data analysis involved 443 Black participants aged 55+ with brain imaging within 1 year of baseline visit in the National Alzheimer's Coordinating Center Uniform Data Set. Chi-square analyses and logistic regression models controlling for demographic variables examined whether active depression in the past 2 years, WMH volume, or their combination were associated with higher odds of all-cause dementia. RESULTS: Depression and higher WMH volume were associated with a higher prevalence of dementia. These associations remained after controlling for demographic factors, as well as vascular disease burden. Dementia risk was highest in the depression/high WMH volume group compared to the depression-only group, high WMH volume-only group, and the no depression/low WMH volume group. Post hoc analyses comparing the Black sample to a demographically matched non-Hispanic White sample showed associations of depression and the combination of depression and higher WMH burden with dementia were greater in Black compared to non-Hispanic White individuals. DISCUSSION: Results suggest late-life depression and WMH have independent and joint relationships with dementia and that Black individuals may be particularly at risk due to these factors.

Cognitive enrichment and education quality moderate cognitive dysfunction in black and white adults with multiple sclerosis.

OBJECTIVE: To examine the extent to which three sociobehavioral proxies of cognitive reserve-years of education, education quality, and cognitive enrichment-differ in their prediction of cognitive performance among Black and White people with MS (PwMS). METHODS: 82 PwMS (Black n = 41, White n = 41) underwent a neurological examination and a neuropsychological evaluation that included tests of word recognition (Wechsler Test of Adult Reading) as well as measures of verbal memory, visuospatial memory, and processing speed (the Brief International Cognitive Assessment for MS; BICAMS). Participants rated their lifetime engagement in various cognitively-enriching activities (Cognitive Reserve Scale). RESULTS: For the full sample, education quality and cognitive enrichment were more strongly associated with cognitive performance than were years of education. Cognitive enrichment was not associated with cognitive performance among participants with high education quality. In contrast, among participants with low education quality, cognitive enrichment was strongly associated with cognitive performance, suggesting that high engagement in cognitively-enriching activities provided similar protection to high education quality. Furthermore, among Black participants, cognitive enrichment and educational quality moderated the relationship between disability level and cognitive performance. In contrast, among White participants, cognitive enrichment did not provide additional protection beyond the buffering effect of education quality. CONCLUSIONS: PwMS can successfully build reserve through multiple routes, including formal education or informal cognitive enrichment. Treatment for MS should incorporate cognitively-enriching activities to build resilience against cognitive decline, particularly for members of marginalized racial/ethnic groups, who are at greatest risk for poor health outcomes, and for whom years of education may not best reflect education quality.

Incremental validity of brief and abbreviated neuropsychological tests toward predicting functional outcomes in multiple sclerosis.

OBJECTIVE: This study examined the relationships among functional outcomes and performance on standard-length and abbreviated cognitive screening measures for multiple sclerosis (MS). METHOD: 72 adults with MS underwent neurological examination and cognitive screening. They completed standard-length and abbreviated versions of tests from the Minimal Assessment of Cognitive Function in MS (MACFIMS), the abbreviated aMACFIMS, and the Brief International Cognitive Assessment for MS (BICAMS). Functional outcomes included neurological disability, physical and psychological dysfunction, and employment status. RESULTS: Concordance of impairment classifications was examined between standard-length and abbreviated tests using logistic regression and ROC curve analyses. Overall, the abbreviated test versions showed a broad range of concordance with impairment classifications made using the full-length tests. Processing speed was the strongest correlate of neurological disability and employment status; immediate recall was the strongest predictor of subjective physical dysfunction. Test performance provided unique value toward predicting neurological disability and employment status, but not physical and psychological dysfunction. CONCLUSIONS: The findings replicate some support for abbreviated tests in MS assessment, although caveats regarding loss of validity associated with abbreviation remain. The findings extend prior research showing that abbreviated tests of processing speed and immediate recall can provide unique predictive information regarding objective functional outcomes.

From Schools to Scans: A Neuroeducational Approach to Comorbid Math and Reading Disabilities.

We bridge two analogous concepts of comorbidity, dyslexia-dyscalculia and reading-mathematical disabilities, in neuroscience and education, respectively. We assessed the cognitive profiles of 360 individuals (mean age 25.79 ± 13.65) with disability in reading alone (RD group), mathematics alone (MD group) and both (comorbidity: MDRD group), with tests widely used in both psychoeducational and neuropsychological batteries. As expected, the MDRD group exhibited reading deficits like those shown by the RD group. The former group also exhibited deficits in quantitative reasoning like those shown by the MD group. However, other deficits related to verbal working memory and semantic memory were exclusive to the MDRD group. These findings were independent of gender, age, or socioeconomic and demographic factors. Through a systematic exhaustive review of clinical neuroimaging literature, we mapped the resulting cognitive profiles to correspondingly plausible neuroanatomical substrates of dyslexia and dyscalculia. In our resulting "probing" model, the complex set of domain-specific and domain-general impairments shown in the comorbidity of reading and mathematical disabilities are hypothesized as being related to atypical development of the left angular gyrus. The present neuroeducational approach bridges a long-standing transdisciplinary divide and contributes a step further toward improved early prediction, teaching and interventions for children and adults with combined reading and math disabilities.

Incisional hernia formation and associated risk factors on a gynecologic oncology service: an exploratory analysis.

PURPOSE: The aim of this study is to identify the rate of incisional hernias and associated risk factors following a vertical midline laparotomy on a gynecologic oncology service. METHODS: This is a retrospective cohort study of patients that underwent a laparotomy through a vertical midline abdominal incision between September 1998 and November 2012. Hernias and various factors were identified including demographics, disease comorbidities, intraoperative variables, and suture technique. Assessment of association with hernia formation was performed using Cox regression and log-rank test. RESULTS: Two hundred and fifty-two patients with follow-up of at least 30 days were identified. Mean age was 59 years (range 21-88 years) and mean BMI was 35.9 kg/m(2) (range 17.2-84.4 kg/m(2)). Sixteen (6.3 %) developed incisional hernias with a median follow-up of 1.7 years (range 1 month to 13 years). The estimate of the 5-year probability of being hernia-free is 86 % (95 % CI 76.5-91.9). Average age of patients who developed a hernia was 66.2 years while average age of those without hernia was 58 years (p < 0.05). There was a significant association of hypertension with incisional hernia occurrence (p = 0.0035, log-rank test). Cancer was present in 100 % of patients that developed hernias and 73 % (172/236) of those that were hernia-free (p = 0.0041, log-rank test). By univariate analysis the risk of developing an incisional hernia was higher, if the abdominal fascia was closed with loop sutures (HR 4.6, 95 % CI 1.49-13.94; p = 0.008). By multivariable analysis incisions closed with loop suture had more than a fivefold increased risk of developing a hernia (HR 5.2, 95 % CI 1.65-16.39; p = 0.005). Presence of both hypertension and utilization of loop sutures had the highest risk of incisional hernia development (HR 7.1, 95 % CI 2.28-22.4; p = 0.001). CONCLUSION: Wound complications including incisional hernias contribute to morbidity in gynecologic oncology patients. Older age, hypertension, utilization of loop sutures, and cancer were found to be associated with hernia formation after laparotomy through a vertical midline abdominal incision. The use of loop sutures to close the abdominal fascia should be investigated further.

Perinuclear distribution of heterochromatin in developing C. elegans embryos.

Specific nuclear domains are nonrandomly positioned within the nuclear space, and this preferential positioning has been shown to play an important role in genome activity and stability. Well-known examples include the organization of repetitive DNA in telomere clusters or in the chromocenter of Drosophila and mammalian cells, which may provide a means to control the availability of general repressors, such as the heterochromatin protein 1 (HP1). We have specifically characterized the intranuclear positioning of in vivo fluorescence of the Caenorhabditis elegans HP1 homologue HPL-2 as a marker for heterochromatin domains in developing embryos. For this purpose, the wavelet transform modulus maxima (WTMM) segmentation method was generalized and adapted to segment the small embryonic cell nuclei in three dimensions. The implementation of a radial distribution algorithm revealed a preferential perinuclear positioning of HPL-2 fluorescence in wild-type embryos compared with the diffuse and homogeneous nuclear fluorescence observed in the lin-13 mutants. For all other genotypes analyzed, the quantitative analysis highlighted various degrees of preferential HPL-2 positioning at the nuclear periphery, which directly correlates with the number of HPL-2 foci previously counted on 2D projections. Using a probabilistic 3D cell nuclear model, we found that any two nuclei having the same number of foci, but with a different 3D probabilistic positioning scheme, can have significantly different counts in the 2D maximum projection, thus showing the deceptive limitations of using techniques of 2D maximum projection foci counts. By this approach, a strong perinuclear positioning of HPL-2 foci was brought into light upon inactivation of conserved chromatin-associated proteins, including the HAT cofactor TRAPP.

Chromosome neighborhood composition determines translocation outcomes after exposure to high-dose radiation in primary cells.

Radiation exposure is an occupational hazard for military personnel, some health care professionals, airport security screeners, and medical patients, with some individuals at risk for acute, high-dose exposures. Therefore, the biological effects of radiation, especially the potential for chromosome damage, are major occupational and health concerns. However, the biophysical mechanisms of chromosome instability subsequent to radiation-induced DNA damage are poorly understood. It is clear that interphase chromosomes occupy discrete structural and functional subnuclear domains, termed chromosome territories (CT), which may be organized into 'neighborhoods' comprising groups of specific CTs. We directly evaluated the relationship between chromosome positioning, neighborhood composition, and translocation partner choice in primary lymphocytes, using a cell-based system in which we could induce multiple, concentrated DNA breaks via high-dose irradiation. We critically evaluated mis-rejoining profiles and tested whether breaks occurring nearby were more likely to fuse than breaks occurring at a distance. We show that CT neighborhoods comprise heterologous chromosomes, within which inter-CT distances directly relate to translocation partner choice. These findings demonstrate that interphase chromosome arrangement is a principal factor in genomic instability outcomes in primary lymphocytes, providing a structural context for understanding the biological effects of radiation exposure, and the molecular etiology of tumor-specific translocation patterns.