Ubiquitous neurocognitive dysfunction in familial adenomatous polyposis: proof-of-concept of the role of APC protein in neurocognitive function.

BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by germline mutations in the APC gene. Patients with FAP have multiple extraintestinal manifestations that follow a genotype-phenotype pattern; however, few data exist characterizing their cognitive abilities. Given the role of the APC protein in development of the central nervous system, we hypothesized that patients with FAP would show differences in cognitive functioning compared to controls. METHODS: Matched case-control study designed to evaluate cognitive function using the Test of Nonverbal Intelligence-4, the Bateria III Woodcock-Munoz, and the Behavior Rating Inventory of Executive Functions-Adult. Twenty-six individuals with FAP (mean age = 34.2 ± 15.0 years) and 25 age-gender and educational level matched controls (mean age = 32.7 ± 13.8 years) were evaluated. RESULTS: FAP-cases had significantly lower IQ (p = 0.005). Across all tasks of the Batería III Woodcock-Muñoz, FAP-cases performed significantly lower than controls, with all of the summary scores falling in the bottom quartile compared to controls (p < 0.0001). Patients with FAP scored within the deficient range for Long-Term Retrieval and Cognitive Fluency. CONCLUSION: APC protein has an important role in neurocognitive function. The pervasive nature of the observed cognitive dysfunction suggests that loss or dysfunction of the APC protein impacts processes in cortical and subcortical brain regions. Additional studies examining larger ethnically diverse cohorts with FAP are warranted.

Altered neural networks and cognition in a hereditary colon cancer.

Familial Adenomatous Polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene presenting with numerous colorectal adenomatous polyps and a near 100% risk of colon cancer. Preliminary research findings from our group indicate that FAP patients experience significant deficits across many cognitive domains. In the current study, fMRI brain metrics in a FAP population and matched controls were used to further the mechanistic understanding of reported cognitive deficits. This research identified and characterized any possible differences in resting brain networks and associations between neural network changes and cognition from 34 participants (18 FAP patients, 16 healthy controls). Functional connectivity analysis was performed using FSL with independent component analysis (ICA) to identify functional networks. Significant differences between cases and controls were observed in 8 well-established resting state networks. With the addition of an aggregate cognitive measure as a covariate, these differences were virtually non-existent, indicating a strong correlation between cognition and brain activity at the network level. The data indicate robust and pervasive effects on functional neural network activity among FAP patients and these effects are likely involved in cognitive deficits associated with this disease.

Measuring HIV felt stigma: a culturally adapted scale targeting PLWHA in Puerto Rico.

The objective of this study was to culturally adapt and validate a scale to measure HIV-related felt stigma in a group of People living with HIV/AIDS (PLWHA) in Puerto Rico. The researchers conducted a two-phase cross-sectional study with 216 participants (60, first phase; 156, second phase). The first phase consisted of the cultural adaptation of the scale; the second evaluated its psychometric properties. After conducting a factor analysis, a 17-item scale, the HIV Felt-Stigma Scale (HFSS), resulted. Participants completed the Puerto Rico Comprehensive Center for the Study of Health Disparities Socio-demographic Questionnaire, the HFSS, the Beck Depression Inventory-II, and the Sexual Abuse dimension of the History of Abuse Questionnaire; the case managers completed the Case Manager Stigma Guide with subjects. The HFSS measures four dimensions: personalized stigma, disclosure concerns, negative self-image, and concern with public attitudes. The alpha and Pearson correlation coefficients (0.91 and 0.68, respectively) indicated satisfactory validity and reliability; the scale suggested adequate convergent validity. The HFSS is a culturally sensitive instrument that fills the existing gap in the measurement of felt stigma in Spanish-speaking PLWHA.

Altered Resting State Brain Networks and Cognition in Familial Adenomatous Polyposis.

Familial Adenomatous Polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene presenting with numerous colorectal adenomatous polyps and a near 100% risk of colon cancer. Preliminary research findings from our group indicate that FAP patients experience significant deficits across many cognitive domains. In the current study, fMRI brain metrics in a FAP population and matched controls were used to further the mechanistic understanding of reported cognitive deficits. This research identified and characterized any possible differences in resting brain networks and associations between neural network changes and cognition from 34 participants (18 FAP patients, 16 healthy controls). Functional connectivity analysis was performed using FSL with independent component analysis (ICA) to identify functional networks. Significant differences between cases and controls were observed in 8 well-established resting state networks. With the addition of an aggregate cognitive measure as a covariate, these differences were virtually non-existent, indicating a strong correlation between cognition and brain activity at the network level. The data indicate robust and pervasive effects on functional neural network activity among FAP patients and these effects are likely involved in cognitive deficits associated with this disease.

Felt Stigma in Injection Drug Users and Sex Workers: Focus Group Research with HIV-Risk Populations in Puerto Rico.

Though many studies have conclusively linked felt stigma and HIV, few have focused on the experiences of rejection felt by members of such socially marginalized groups as intravenous drug users (IDU) and sex workers (SW). Using focus groups, our study explored these experiences in 34 individuals (17 male UDUs and 17 female SWs) at risk of becoming infected with HIV, the objective being to discover why they engaged in maladaptive behaviors as a way of coping with felt stigma. We used deductive and inductive analysis to codify the resulting data. Concepts associated with the word stigma, emotional reactions to felt stigma, and the impact of felt stigma on self-schema helped elucidate how the internalization of felt stigma can lead to negative affective states and self-destructive behaviors (e.g., drug use and syringe exchange). Results underline the importance of developing intervention models that reduce stigma as a means of HIV prevention in vulnerable populations.