Attention and Memory in Depersonalization-Spectrum Dissociative Disorders: Impact of Selective-Divided Attentional Condition, Stimulus Emotionality, and Stress.

We investigated cognition in depersonalization-spectrum dissociative disorders without comorbid posttraumatic stress disorder to explore evidence for emotionally avoidant information processing. Forty-eight participants with DSM-IV dissociative disorder (DD) (Depersonalization Disorder - 37, Dissociative Disorder NOS -11), 36 participants with Posttraumatic Stress Disorder (PTSD), and 56 healthy controls (HC) were administered the Weschler Adult Intelligence Scale-III (WAIS); the Weschler Memory Scale-III (WMS); and three Stroop tasks: the Standard Stroop, a selective-attention Emotional Stroop using neutral, dissociation, and trauma-related word categories, and a divided-attention Emotional Stroop using comparable words. Participants were also administered a paired-associates explicit and implicit memory test using emotionally neutral and negative words, before and after the Trier Social Stress Test. The DD and HC groups had comparable general intelligence and memory scores, though dissociation severity was inversely related to verbal comprehension and working memory. In the selective-attention condition, DD participants showed greater incidental recall across word categories with comparable interference. However in the divided-attention condition, DD participants significantly favored lesser attentional interference at the expense of remembering words. Across attentional conditions, DD participants had better recall for disorder-related than neutral words. Pre-stress, the DD group demonstrated better explicit memory for neutral versus negative words with reversal after stress, whereas the HC group demonstrated the opposite pattern; implicit memory did not differ. Cognition in the PTSD control group was generally dissimilar to the DD group. The findings in toto provide substantial evidence for emotionally avoidant information processing in DD, vulnerable to the impact of stress, at the level of both attention and memory.

Assessing the Validity of Self-Reports of Marijuana Use among Adolescents Entering the Juvenile Justice System: Gender Differences.

Objective: Scant research exists on the validity of self-reported marijuana use using biological assays among adolescents involved in the juvenile justice system. This exploratory study examined gender (sex) differences in underreporting of marijuana use and the impact of age, race/ethnicity, living situation, depression, family problems, sexual risk behaviors, previous drug treatment, and juvenile justice placement. Methods: Self-reports of past year marijuana use were validated with urinalysis, and those testing positive for marijuana use were selected for study. The sample was 256 females and 885 males, aged 12 to 18, entering an urban juvenile assessment center in a southeastern U.S. state between 2017 and 2019. Results: Results indicated significant differences in marijuana underreporting (tested positive but self-reported no use), with 37% of females and 55% of males underreporting use. For males, Hispanic ethnicity, African American race, sexually transmitted infection (STI), and secure detention placement increased the odds of underreporting, while having an incarcerate parent and previous drug treatment decreased the odds. For females, number of sexual partners decreased the odds of underreporting of marijuana use. Conclusion: These findings imply use of collateral information, such as urine tests, as a recommendation for juvenile justice intake to corroborate self-reports and guide risk assessment.

Individual- and Community-Level Factors in the STD Status of Justice-Involved Youth: Multi-Group, Exploratory Two-Level Analysis.

Justice-involved youth display higher prevalence rates of sexually transmitted diseases (STDs), in comparison with youth in the general population, highlighting a critical public health concern. Individual factors are important predictors of STDs, but only provide a partial understanding of this public health issue. Communities experiencing higher levels of disorder and lower levels of cohesion tend to have fewer institutional resources available, which may impact sexual risk behavior and STDs. However, few studies have examined the association between community characteristics and STD prevalence among adolescents. The current study examined community-level (n = 106) characteristics and individual-level attributes in explaining STDs among justice-involved youth (n = 1233: n = 515 female; n = 718 male). At the individual level, results showed older males and those with more drug-related problems were more likely to be STD positive, while females with more sexual partners and those with less drug-related problems were more likely to be STD positive. At the community level, females residing in areas with fewer educated residents were more likely to be STD positive. These gender differences were significant, suggesting a gendered perspective is important for understanding STD infection. The justice system represents a critical opportunity in the treatment and prevention of STDs for youth.

Distinct age-related associations for body mass index and cognition in cognitively healthy very old veterans.

ABSTRACTAssociations between high body mass index (BMI) and subsequent cognitive decline, reported in elderly averaging below age 75, become less consistent at older ages. We compared the associations of BMI with cognition in moderately old (ages 75-84, N = 154) and oldest-old (85+, N = 93) samples. BMI and cognition were assessed cross-sectionally in cognitively intact elderly (mean age = 84.5, SD = 4.4) male veterans. Regression analyses of three cognitive domains - executive functions/language, attention, and memory-compared relationship with BMI between the moderately old and oldest-old. Higher BMI was associated with relatively poorer executive functions/language performance in the moderately old, while the opposite relationship, higher BMI associated with relatively better performance, was found in the oldest-old. Associations for the other two cognitive domains did not differ significantly between age groups. The reversal of association direction for executive functions/language performance with higher BMI is consistent with the protected survivor model. This model posits a minority subpopulation with a protective factor-genetic or otherwise-against both mortality and cognitive decline associated with risk factor status. The very old who remain cognitively intact despite the presence of risk factors are more likely to possess protection.

Depression is more strongly associated with cognition in elderly women than men with type 2 diabetes.

Depression and cognitive impairment are highly prevalent in type 2 diabetes (T2D), yet little is known about how their relationship varies by sex. We examined this question in a large T2D sample (N = 897) of non-demented elderly (≥ 65) participating in the Israel Diabetes and Cognitive Decline (IDCD) Study. Cognition was evaluated by a comprehensive neuropsychological battery and depressive symptoms were assessed by the Geriatric Depression Scale (GDS). The results showed that in all but the executive function domain, the association of depressive symptoms with poorer cognitive function was stronger in women than men, with a significant interaction for language/semantic categorization and missed significance for episodic memory. When defining clinical depression as GDS of ≥6, women with depression had significantly poorer language/semantic categorization, episodic memory, and overall cognitive function. Inclusion of antidepressants in the model did not alter substantively the associations. Our results suggest that depressed T2D women may have poorer cognitive performance, highlighting the significance of sex-specific personalized management of depression in elderly diabetics.

The human-specific CASP4 gene product contributes to Alzheimer-related synaptic and behavioural deficits.

Recent studies have indicated that innate immune signalling molecules are involved in late-onset Alzheimer's disease (LOAD) risk. Amyloid beta (Aß) accumulates in AD brain, and has been proposed to act as a trigger of innate immune responses. Caspase-4 is an important part of the innate immune response. We recently characterized transgenic mice carrying human CASP4, and observed that the mice manifested profound innate immune responses to lipopolysaccharide (LPS). Since these inflammatory processes are important in the aetiology of AD, we have now analysed the correlation of expression of caspase-4 in human brain with AD risk genes, and studied caspase-4 effects on AD-related phenotypes in APPswe/PS1deltaE9 (APP/PS1) mice. We observed that the expression of caspase-4 was strongly correlated with AD risk genes including TYROBP, TREM2, CR1, PSEN1, MS4A4A and MS4A6A in LOAD brains. Caspase-4 expression was upregulated in CASP4/APP/PS1 mice in a region-specific manner, including hippocampus and prefrontal cortex. In APP/PS1 mice, caspase-4 expression led to impairments in the reversal phase of a Barnes maze task and in hippocampal synaptic plasticity, without affecting soluble or aggregated Aß levels. Caspase-4 was expressed predominantly in microglial cells, and in the presence of CASP4, more microglia were clustered around amyloid plaques. Furthermore, our data indicated that caspase-4 modulates microglial cells in a manner that increases proinflammatory processes. We propose that microglial caspase-4 expression contributes to the cognitive impairments in AD, and that further study of caspase-4 will enhance our understanding of AD pathogenesis and may lead to novel therapeutic targets in AD.

Outcome age-based prediction of successful cognitive aging by total cholesterol.

INTRODUCTION: Some associations of high total cholesterol with dementia risk diminish as the outcome age-age at cognitive assessment-increases. METHODS: The Framingham Heart Study provided 1897 participants with intact cognition at entry. Cox regression analysis for incident marked cognitive decline included "time-dependent" coefficients, with associations between total cholesterol and covariates changing by outcome age. Decline within age categories of 75-84 and 85-94 years was also examined. RESULTS: Significant associations of rising total cholesterol linear slope, low entry age, low education, and statin nonuse with risk diminished significantly by outcome age. At 85-94 years, falling linear slope was significant. DISCUSSION: The protected survival model posits a minority subpopulation with protection against mortality and cognitive decline associated with total cholesterol risk factors. It predicts the observed diminished or reversed cholesterol associations with increasing age. Protection is particularly likely for successful cognitive aging-intact cognition at very old age-despite increased risk from cholesterol.

A Multigroup, Longitudinal Study of Truant Youths, Marijuana Use, Depression, and STD-Associated Sexual Risk Behavior.

Truant youth are likely to engage in a number of problem behaviors, including sexual risky behaviors. Previous research involving non-truant youth has found sexual risk behaviors to be related to marijuana use and depression, with differential effects for male and female youth. Using data collected in a NIDA funded, prospective intervention project, results are reported of a male-female, multi-group, longitudinal analysis of the relationships among truant youth baseline sexual risk behavior, marijuana use, and depression, and their sexual risk behavior over four follow-up time points. Results indicated support for the longitudinal model, with female truants having higher depression scores, and showing stronger relationships between baseline depression and future engagement in sexual risk behavior, than male truants. Findings suggest that incorporating strategies to reduce depression and marijuana use may decrease youth sexual risk behavior.

Ethnicity/culture modulates the relationships of the haptoglobin (Hp) 1-1 phenotype with cognitive function in older individuals with type 2 diabetes.

OBJECTIVE: The haptoglobin (Hp) genotype has been associated with cognitive function in type 2 diabetes. Because ethnicity/culture has been associated with both cognitive function and Hp genotype frequencies, we examined whether it modulates the association of Hp with cognitive function. METHODS: This cross-sectional study evaluated 787 cognitively normal older individuals (>65 years of age) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline study. Interactions in two-way analyses of covariance compared Group (Non-Ashkenazi versus Ashkenazi Jews) on the associations of Hp phenotype (Hp 1-1 versus non- Hp 1-1) with five cognitive outcome measures. The primary control variables were age, gender, and education. RESULTS: Compared with Ashkenazi Jews, non-Ashkenazi Jews with the Hp 1-1 phenotype had significantly poorer cognitive function than non-Hp 1-1 in the domains of Attention/Working Memory (p = 0.035) and Executive Function (p = 0.023), but not in Language/Semantic Categorization (p = 0.432), Episodic Memory (p = 0.268), or Overall Cognition (p = 0.082). After controlling for additional covariates (type 2 diabetes-related characteristics, cardiovascular risk factors, Mini-mental State Examination, and extent of depressive symptoms), Attention/Working Memory (p = 0.038) and Executive Function (p = 0.013) remained significant. CONCLUSIONS: Older individuals from specific ethnic/cultural backgrounds with the Hp 1-1 phenotype may benefit more from treatment targeted at decreasing or halting the detrimental effects of Hp 1-1 on the brain. Future studies should examine differential associations of Hp 1-1 and cognitive impairment, especially for groups with high prevalence of both, such as African-Americans and Hispanics.

Waist circumference is correlated with poorer cognition in elderly type 2 diabetes women.

INTRODUCTION: Waist circumference is associated with type 2 diabetes (T2D) and cognition, yet the relationship between waist circumference and cognition in individuals with T2D is not well understood. METHODS: We studied the relationship of waist circumference with five cognitive outcomes (executive functioning, language/semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 845 cognitively normal elderly with type 2 diabetes (T2D). RESULTS: In women, waist circumference was correlated with significantly lower language and/or semantic categorization performance (P < .0001), executive functioning (P = .026), and overall cognition (P = .003) after controlling for age, education, BMI, and cardiovascular, diabetes-related, APOE ε4, and inflammatory potential confounders. Attention/working memory (P = .532) and episodic memory (P = .144) were not associated with waist circumference. These correlations were not found in men. DISCUSSION: These results suggest that central adiposity in elderly women with T2D may increase their risk for dementia.

Longitudinal Effects of a Second-Order Multi-Problem Factor of Sexual Risk, Marijuana Use, and Delinquency on Future Arrest Among Truant Youths.

Based on problem-behavior theory (Jessor & Jessor, 1977), a second-order problem behavior model of delinquency, marijuana use, and risky sexual behavior over five waves was estimated among truant adolescents. The study also investigated the influence of the problem factor on future arrest charges and the effect of socio-demographics on problem behavior and future crime. Results confirm the existence of a second-order latent factor of problem behaviors. Problem behaviors predicted more future arrest charges. Age was related to problem behaviors and future arrest charges, and family income was related to problem behavior. Implications for future research and practice are discussed.

Impact of Brief Intervention Services on Drug-Using Truant Youths' Self-Reported Delinquency and Arrest Charges: A Longitudinal Study.

The issue of delinquency among truant youth is insufficiently documented in the literature. There is a need to elucidate this issue, and assess the efficacy of interventions to reduce this problem behavior. The present, NIDA-funded study addressed this gap by examining the impact of a Brief Intervention (BI), originally designed to address youth substance use, on their delinquent behavior over an 18-month follow-up period (for self-reported delinquency) and a 24-month follow-up period (for official record delinquency). A number of significant BI intervention effects with sizable effect sizes were found, as well as a number of marginally significant BI effects. In particular, significant reductions in arrest charges at 24-month follow-up for youth receiving BI services compared to controls were among the key findings of this study. Service delivery implications and directions for future analyses are discussed.

Neuropsychological Test Performance in Cognitively Normal Spanish-speaking Nonagenarians with Little Education.

To find associations of age, sex, and education with neuropsychological test performance in cognitively normal Spanish-speaking Costa Rican nonagenarians with little education; to provide norms; and to compare their performance with similar Puerto Ricans. For 95 Costa Ricans (90-102 years old, 0-6 years of education), multiple regression assessed associations with demographics of performance on six neuropsychological tests. Analyses of covariance compared them with 23 Puerto Ricans (90-99 years old). Younger age and being female-but not education-were associated with better performance on some neuropsychological tests, in particular episodic memory. The Puerto Ricans performed better on learning and memory tasks. In cognitively intact Spanish-speaking nonagenarians with little or no education, education did not affect test performance. Additional studies of the effect of education on cognitive performance are warranted in other samples with extremely low education or old age. National differences in performance highlight the importance of group-specific norms.

Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes.

AIMS/HYPOTHESIS: The purpose of this study was to investigate whether the association of glycaemic control with cognitive function is modulated by the haptoglobin 1-1 (Hp 1-1) genotype in cognitively normal elderly individuals with type 2 diabetes. METHODS: In this cross-sectional study, we examined 793 participants who were genotyped for Hp (80 Hp 1-1 carriers and 713 Hp 1-1 non-carriers) enrolled in the Israel Diabetes and Cognitive Decline (IDCD) study. Glycaemic control was operationally defined by HbA1c level. The outcome measures were performance in four cognitive domains (episodic memory, attention/working memory, language/semantic categorisation, executive function) and overall cognition, a composite of the domains. Effect sizes were obtained from hierarchical linear regression analyses for each outcome measure, controlling for demographics, type 2 diabetes-related characteristics, cardiovascular risk factors, and their interactions with Hp genotype. RESULTS: Interaction analyses showed significantly stronger associations of HbA1c with poorer cognitive function among Hp 1-1 carriers than non-carriers; attention/working memory (p < 0.001) and overall cognition (p = 0.003). For these two cognitive domains, associations were significant for Hp 1-1 carriers despite the small sample size (p < 0.00001 and p = 0.001, respectively), but not for non-carriers. CONCLUSIONS/INTERPRETATION: Our findings suggest that patients with type 2 diabetes and poor glycaemic control carrying the Hp 1-1 genotype may be at increased risk of cognitive impairment, particularly in the attention/working memory domain. The association of glycaemic control with this domain may indicate cerebrovascular mechanisms.

Glycemic control, inflammation, and cognitive function in older patients with type 2 diabetes.

OBJECTIVE: Glycated hemoglobin (HbA1c) and C-reactive protein (CRP) have been associated with cognitive impairment independently. However, it is unclear if their combination exacerbates poor cognitive function. We assessed whether long-term glycemic level and glycemic variability modulate the association of systemic inflammation with cognitive function, in a sample of cognitively normal older people with type 2 diabetes. METHODS: A retrospective cohort study of 777 randomly selected participants from ~11,000 patients in the Maccabi Healthcare Services Diabetes Registry, as part of the Israel Diabetes and Cognitive Decline study. Subjects averaged 18 (±9.4) HbA1c measures in the Maccabi Healthcare Services Registry, which were used to calculate long-term glycemic level (HbA1c-mean) and glycemic variability (HbA1c-standard deviation (SD)). Linear regression models assessed the interactions of CRP, a marker of systemic inflammation, with HbA1c-mean and HbA1c-SD on subjects' performance in tests of Memory, Executive Functions, Attention, and Semantic Categorization. RESULTS: Quadratic interactions of CRP with HbA1c-SD approached significance for executive functions and overall cognition. However, after Bonferroni adjustment, none of the interactions of CRP with HbA1c were statistically significant. In partial correlations according to HbA1c-SD tertiles, CRP was weakly correlated in the middle tertile with decreased performance in the domains of semantic categorization (r = -0.166, p = 0.011), executive functions (r = -0.136, p = 0.038), and overall cognition (r = -0.157, p = 0.016). CONCLUSIONS: Glycated hemoglobin does not substantially modulate the association of CRP with cognition in a sample of cognitively normal, community dwelling older people with relatively well-managed type 2 diabetes.

Association of apolipoprotein E-e4 and dementia declines with age.

OBJECTIVE: To study the association of dementia with apolipoprotein E-e4 (APOE-e4) and its interaction with age in a nonagenarian Costa Rican group (N-sample) and a general elderly contrast group (GE-sample). METHODS: In both case-control studies, participants were cognitively intact or diagnosed with dementia. The N-sample (N = 112) was at least age 90 years; the GE-sample (N = 98) was at least age 65 years. RESULTS: Dementia and APOE-e4 were not significantly associated in the N-sample, but were in the GE-sample. There was a significant interaction of age with APOE-e4 in the N-sample, but not in the GE-sample. Descriptively dividing the N-sample at the median (age 93 years) showed a group interaction: APOE-e4 was more associated with dementia in the younger N-sample than in the older N-sample, where six of seven APOE-e4 carriers were cognitively intact. CONCLUSIONS: The results support the reduction in association of APOE-e4 with dementia in extreme old age, consistent with a survivor effect model for successful cognitive aging.

The association of duration of type 2 diabetes with cognitive performance is modulated by long-term glycemic control.

OBJECTIVES: It is unclear why duration of type 2 diabetes (T2D) is associated with increased cognitive compromise. High hemoglobin A1c (HbA1c) has also been associated with dementia, and is the primary contributor to T2D complications. Here we investigated whether the association of duration of T2D with cognitive functioning is modulated by HbA1C levels. METHODS: This study examined nondemented community-dwelling T2D elderly (N = 897) participating in the Israel Diabetes and Cognitive Decline study, who were assessed with a broad neuropsychological battery. Subjects were all from the Maccabi Healthcare Services, which has a Diabetes Registry with complete HbA1c measurements since 1998. Partial correlations were performed to examine the modulating effect of HbA1c on the relationship of duration of T2D with five cognitive measures, controlling for sociodemographic and cardiovascular risk factors. RESULTS: An interaction of duration of T2D with HbA1c was associated with executive functioning (p = 0.006), semantic categorization (p = 0.019), attention/working memory (p = 0.011), and overall cognition (p = 0.006), such that the associations between duration of T2D and cognitive impairment increased as HbA1c levels increased-but not for episodic memory (p = 0.984). CONCLUSIONS: Because duration of T2D was associated with cognition in higher HbA1c levels and overall no associations were found in lower HbA1c levels, our results suggest that individuals with T2D may limit their risk of future cognitive decline by maintaining long-term good glycemic control.

Neuropsychological and neuropsychiatric prediction of global cognitive status among older Spanish-speaking Hispanics and English-speaking whites.

BACKGROUND: Neuropsychological and depression measures have been found to predict cognitive functioning. We compared these associations among whites and Spanish-speaking Hispanics. METHODS: Fifty-two pairs of whites and Hispanics were matched demographically and clinically in a cross-sectional study. Hierarchical regression analyses predicted Global Deterioration Scale (GDS) rating by baseline neuropsychological tests and depression symptoms. RESULTS: Neuropsychological tests predicted GDS better in whites; depression symptoms--specifically retardation--predicted well in Hispanics but not whites. Immediate recall of the New York University (NYU)-Paragraph Test and the Retardation item of the Hamilton Depression Rating Scale were associated with GDS in Hispanics and delayed recall of the NYU-Paragraph Test and Wechsler Adult Intelligence Scale-Digit Symbol in whites. Neuropsychological tests and depression symptoms predicted GDS differently in Hispanics and whites. DISCUSSION: These results suggest that other measures should be considered to increase the predictive accuracy of neuropsychological tests when assessing cognitive status in Spanish-speaking Hispanics. Additional studies of specific ethnic/racial and sociodemographic subgroups are warranted.

Age, gender, and education are associated with cognitive performance in an older Israeli sample with type 2 diabetes.

OBJECTIVE: To evaluate the relationships of age, education, and gender with performance on neuropsychological tests in a cognitively intact, older Israeli sample with type 2 diabetes (T2D). METHODS: We examined 862 participants, 65-84 years old, enrolled in the Israel Diabetes and Cognitive Decline study. Multiple regression assessed associations of performance on 17 neuropsychological tests, including the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery, with age, education, and gender. RESULTS: Higher education and younger age were consistently associated with better performance. Women outperformed men on all memory tasks; men outperformed women on two non-verbal measures. These patterns of demographic associations with cognitive performance were very similar to those of US cohorts. CONCLUSIONS: In a cognitively intact, older Israeli sample with T2D, better test performance is associated primarily with higher education, followed by younger age and gender differences. Although T2D is associated with cognitive deficits, it recapitulates the patterns of relationships between cognitive performance and demographic characteristics seen in non-T2D diabetic samples.

The Israel Diabetes and Cognitive Decline (IDCD) study: Design and baseline characteristics.

BACKGROUND: Type 2 diabetes (T2D) is associated with increased risk of dementia. The prospective longitudinal Israel Diabetes and Cognitive Decline study aims at identifying T2D-related characteristics associated with cognitive decline. METHODS: Subjects are population-based T2D 65+, initially cognitively intact. Medical conditions, blood examinations, and medication use data are since 1998; cognitive, functional, demographic, psychiatric, DNA, and inflammatory marker study assessments were conducted every 18 months. Because the duration of T2D reflects its chronicity and implications, we compared short (0-4.99 years), moderate (5-9.99), and long (10+) duration for the first 897 subjects. RESULTS: The long duration group used more T2D medications, had higher glucose, lower glomerular filtration rate, slower walking speed, and poorer cognitive functioning. Duration was not associated with most medical, blood, urine, and vital characteristics. CONCLUSIONS: Tracking cognition, with face-to-face evaluations, exploiting 15 years of historical detailed computerized, easily accessible, and validated T2D-related characteristics may provide novel insights into T2D-related dementia.