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Evaluating pauses in natural speech is a promising strategy for improving reliability, validity, and efficiency in assessing cognitive functions in people with mild cognitive impairment (MCI) and Alzheimer’s dementia (AD).
Method:
We conducted a quantitative meta-analysis of studies employing automated pause analysis. We included measures of speaking rate for comparison.
Results:
We identified 13 studies evaluating pause measures and 8 studies of speaking rate in people with MCI (n’s = 276 & 109, respectively) and AD (n’s = 170 & 81, respectively) and healthy aged controls (n’s = 492 & 231, respectively). Studies evaluated speech across various tasks, including standard neuropsychological, reading, and free/conversational tasks. People with AD and MCI showed longer pauses than controls at approximately 1.20 and 0.62 standard deviations, respectively, though there was substantial heterogeneity across studies. A more modest effect, of 0.66 and 0.27 SDs, was observed between these groups in speech rate. The largest effects were observed for standardized memory tasks.
Conclusions:
Of the many ways that speech can be objectified, pauses appear particularly important for understanding cognition in AD. Pause analysis has the benefit of being face valid, interpretable in ratio format as a reaction time, tied to known socio-cognitive functions, and relatively easy to measure, compute, and interpret. Automation of speech analysis can greatly expand the assessment of AD and potentially improve early identification of one of the most devastating and costly diseases affecting humans.
Evidence indicates hypervitaminosis A may be attributed to overconsumption of natural preformed vitamin A (VA) and overlapping VA intervention strategies. Hypervitaminosis A can disrupt metabolic processes; however, the extent and mechanisms of these impacts are not well understood. This study aims to assess metabolic differences related to hypervitaminosis A and VA supplementation by performing metabolomics analysis. A subsample of South African preschoolers participating in the country’s VA supplementation programme was selected. Participants were divided into two groups: adequate VA (n 15; 0·59–0·99 µmol/g total liver reserve and high VA (n 15; ≥ 1·0 µmol/g total liver reserve). Serum samples were collected at baseline and 28 d after consuming a 200 000 IU VA supplement. Lipidomics and oxylipins assays were conducted using ultraperformance LC-MS. At baseline, unsaturated lysophosphatidylcholines and unsaturated phosphatidylcholines were significantly lower in the high VA group (P < 0·05). A group-by-time interaction with VA supplementation was observed for polyunsaturated lysophosphatidylcholines and polyunsaturated phosphatidylcholines (P < 0·05). Additionally, a group effect was noted for oxylipins, and a time effect in response to VA supplementation was seen with decreased arachidonic acid and lipoxygenase- and non-enzymatically derived oxylipins (P < 0·05). Hypervitaminosis A is associated with modifications in lipids involved in cell structure and signalling, particularly unsaturated lysophosphatidylcholines and phosphatidylcholines. Further research is needed to identify the mechanisms behind these modifications, their physiological effects and their potential as biomarkers of elevated vitamin A status.
Understanding the factors contributing to optimal cognitive function throughout the aging process is essential to better understand successful cognitive aging. Processing speed is an age sensitive cognitive domain that usually declines early in the aging process; however, this cognitive skill is essential for other cognitive tasks and everyday functioning. Evaluating brain network interactions in cognitively healthy older adults can help us understand how brain characteristics variations affect cognitive functioning. Functional connections among groups of brain areas give insight into the brain’s organization, and the cognitive effects of aging may relate to this large-scale organization. To follow-up on our prior work, we sought to replicate our findings regarding network segregation’s relationship with processing speed. In order to address possible influences of node location or network membership we replicated the analysis across 4 different node sets.
Participants and Methods:
Data were acquired as part of a multi-center study of 85+ cognitively normal individuals, the McKnight Brain Aging Registry (MBAR). For this analysis, we included 146 community-dwelling, cognitively unimpaired older adults, ages 85-99, who had undergone structural and BOLD resting state MRI scans and a battery of neuropsychological tests. Exploratory factor analysis identified the processing speed factor of interest. We preprocessed BOLD scans using fmriprep, Ciftify, and XCPEngine algorithms. We used 4 different sets of connectivity-based parcellation: 1)MBAR data used to define nodes and Power (2011) atlas used to determine node network membership, 2) Younger adults data used to define nodes (Chan 2014) and Power (2011) atlas used to determine node network membership, 3) Older adults data from a different study (Han 2018) used to define nodes and Power (2011) atlas used to determine node network membership, and 4) MBAR data used to define nodes and MBAR data based community detection used to determine node network membership.
Segregation (balance of within-network and between-network connections) was measured within the association system and three wellcharacterized networks: Default Mode Network (DMN), Cingulo-Opercular Network (CON), and Fronto-Parietal Network (FPN). Correlation between processing speed and association system and networks was performed for all 4 node sets.
Results:
We replicated prior work and found the segregation of both the cortical association system, the segregation of FPN and DMN had a consistent relationship with processing speed across all node sets (association system range of correlations: r=.294 to .342, FPN: r=.254 to .272, DMN: r=.263 to .273). Additionally, compared to parcellations created with older adults, the parcellation created based on younger individuals showed attenuated and less robust findings as those with older adults (association system r=.263, FPN r=.255, DMN r=.263).
Conclusions:
This study shows that network segregation of the oldest-old brain is closely linked with processing speed and this relationship is replicable across different node sets created with varied datasets. This work adds to the growing body of knowledge about age-related dedifferentiation by demonstrating replicability and consistency of the finding that as essential cognitive skill, processing speed, is associated with differentiated functional networks even in very old individuals experiencing successful cognitive aging.
Cognitive training has shown promise for improving cognition in older adults. Aging involves a variety of neuroanatomical changes that may affect response to cognitive training. White matter hyperintensities (WMH) are one common age-related brain change, as evidenced by T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) MRI. WMH are associated with older age, suggestive of cerebral small vessel disease, and reflect decreased white matter integrity. Higher WMH load associates with reduced threshold for clinical expression of cognitive impairment and dementia. The effects of WMH on response to cognitive training interventions are relatively unknown. The current study assessed (a) proximal cognitive training performance following a 3-month randomized control trial and (b) the contribution of baseline whole-brain WMH load, defined as total lesion volume (TLV), on pre-post proximal training change.
Participants and Methods:
Sixty-two healthy older adults ages 65-84 completed either adaptive cognitive training (CT; n=31) or educational training control (ET; n=31) interventions. Participants assigned to CT completed 20 hours of attention/processing speed training and 20 hours of working memory training delivered through commercially-available Posit Science BrainHQ. ET participants completed 40 hours of educational videos. All participants also underwent sham or active transcranial direct current stimulation (tDCS) as an adjunctive intervention, although not a variable of interest in the current study. Multimodal MRI scans were acquired during the baseline visit. T1- and T2-weighted FLAIR images were processed using the Lesion Segmentation Tool (LST) for SPM12. The Lesion Prediction Algorithm of LST automatically segmented brain tissue and calculated lesion maps. A lesion threshold of 0.30 was applied to calculate TLV. A log transformation was applied to TLV to normalize the distribution of WMH. Repeated-measures analysis of covariance (RM-ANCOVA) assessed pre/post change in proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures in the CT group compared to their ET counterparts, controlling for age, sex, years of education and tDCS group. Linear regression assessed the effect of TLV on post-intervention proximal composite and sub-composite, controlling for baseline performance, intervention assignment, age, sex, years of education, multisite scanner differences, estimated total intracranial volume, and binarized cardiovascular disease risk.
Results:
RM-ANCOVA revealed two-way group*time interactions such that those assigned cognitive training demonstrated greater improvement on proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures compared to their ET counterparts. Multiple linear regression showed higher baseline TLV associated with lower pre-post change on Processing Speed Training sub-composite (ß = -0.19, p = 0.04) but not other composite measures.
Conclusions:
These findings demonstrate the utility of cognitive training for improving postintervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appear to be particularly sensitive to white matter hyperintensity load versus working memory training change. These data suggest that TLV may serve as an important factor for consideration when planning processing speed-based cognitive training interventions for remediation of cognitive decline in older adults.
Although anesthesiology and endocrinology are two distinct branches of medicine, some recent breakthrough treatments have brought together both medical specialties, particularly those concerned with surgical sciences and critical care. Related to the use of various traditional surgical techniques, the lack of newer and safer drugs, the lack of monitoring tools, and the scarcity of critical care services in the past, managing patients with various endocrine disorders has always been perceived as being more difficult by practicing anesthesiologists.
Cannabis use has been linked to psychotic disorders but this association has been primarily observed in the Global North. This study investigates patterns of cannabis use and associations with psychoses in three Global South (regions within Latin America, Asia, Africa and Oceania) settings.
Methods
Case–control study within the International Programme of Research on Psychotic Disorders (INTREPID) II conducted between May 2018 and September 2020. In each setting, we recruited over 200 individuals with an untreated psychosis and individually-matched controls (Kancheepuram India; Ibadan, Nigeria; northern Trinidad). Controls, with no past or current psychotic disorder, were individually-matched to cases by 5-year age group, sex and neighbourhood. Presence of psychotic disorder assessed using the Schedules for Clinical Assessment in Neuropsychiatry and cannabis exposure measured by the World Health Organisation Alcohol, Smoking and Substance Involvement Screening Test (ASSIST).
Results
Cases reported higher lifetime and frequent cannabis use than controls in each setting. In Trinidad, cannabis use was associated with increased odds of psychotic disorder: lifetime cannabis use (adj. OR 1.58, 95% CI 0.99–2.53); frequent cannabis use (adj. OR 1.99, 95% CI 1.10–3.60); cannabis dependency (as measured by high ASSIST score) (adj. OR 4.70, 95% CI 1.77–12.47), early age of first use (adj. OR 1.83, 95% CI 1.03–3.27). Cannabis use in the other two settings was too rare to examine associations.
Conclusions
In line with previous studies, we found associations between cannabis use and the occurrence and age of onset of psychoses in Trinidad. These findings have implications for strategies for prevention of psychosis.
Extensive evidence indicates that rates of psychotic disorder are elevated in more urban compared with less urban areas, but this evidence largely originates from Northern Europe. It is unclear whether the same association holds globally. This study examined the association between urban residence and rates of psychotic disorder in catchment areas in India (Kancheepuram, Tamil Nadu), Nigeria (Ibadan, Oyo), and Northern Trinidad.
Methods
Comprehensive case detection systems were developed based on extensive pilot work to identify individuals aged 18–64 with previously untreated psychotic disorders residing in each catchment area (May 2018–April/May/July 2020). Area of residence and basic demographic details were collected for eligible cases. We compared rates of psychotic disorder in the more v. less urban administrative areas within each catchment area, based on all cases detected, and repeated these analyses while restricting to recent onset cases (<2 years/<5 years).
Results
We found evidence of higher overall rates of psychosis in more urban areas within the Trinidadian catchment area (IRR: 3.24, 95% CI 2.68–3.91), an inverse association in the Nigerian catchment area (IRR: 0.68, 95% CI 0.51–0.91) and no association in the Indian catchment area (IRR: 1.18, 95% CI 0.93–1.52). When restricting to recent onset cases, we found a modest positive association in the Indian catchment area.
Conclusions
This study suggests that urbanicity is associated with higher rates of psychotic disorder in some but not all contexts outside of Northern Europe. Future studies should test candidate mechanisms that may underlie the associations observed, such as exposure to violence.
To evaluate the construct validity of the NIH Toolbox Cognitive Battery (NIH TB-CB) in the healthy oldest-old (85+ years old).
Method:
Our sample from the McKnight Brain Aging Registry consists of 179 individuals, 85 to 99 years of age, screened for memory, neurological, and psychiatric disorders. Using previous research methods on a sample of 85 + y/o adults, we conducted confirmatory factor analyses on models of NIH TB-CB and same domain standard neuropsychological measures. We hypothesized the five-factor model (Reading, Vocabulary, Memory, Working Memory, and Executive/Speed) would have the best fit, consistent with younger populations. We assessed confirmatory and discriminant validity. We also evaluated demographic and computer use predictors of NIH TB-CB composite scores.
Results:
Findings suggest the six-factor model (Vocabulary, Reading, Memory, Working Memory, Executive, and Speed) had a better fit than alternative models. NIH TB-CB tests had good convergent and discriminant validity, though tests in the executive functioning domain had high inter-correlations with other cognitive domains. Computer use was strongly associated with higher NIH TB-CB overall and fluid cognition composite scores.
Conclusion:
The NIH TB-CB is a valid assessment for the oldest-old samples, with relatively weak validity in the domain of executive functioning. Computer use’s impact on composite scores could be due to the executive demands of learning to use a tablet. Strong relationships of executive function with other cognitive domains could be due to cognitive dedifferentiation. Overall, the NIH TB-CB could be useful for testing cognition in the oldest-old and the impact of aging on cognition in older populations.
There is evidence of an association between life events and psychosis in Europe, North America and Australasia, but few studies have examined this association in the rest of the world.
Aims
To test the association between exposure to life events and psychosis in catchment areas in India, Nigeria, and Trinidad and Tobago.
Method
We conducted a population-based, matched case–control study of 194 participants in India, Nigeria, and Trinidad and Tobago. Cases were recruited through comprehensive population-based, case-finding strategies. The Harvard Trauma Questionnaire was used to measure life events. The Screening Schedule for Psychosis was used to screen for psychotic symptoms. The association between psychosis and having experienced life events (experienced or witnessed) was estimated by conditional logistic regression.
Results
There was no overall evidence of an association between psychosis and having experienced or witnessed life events (adjusted odds ratio 1.19, 95% CI 0.62–2.28). We found evidence of effect modification by site (P = 0.002), with stronger evidence of an association in India (adjusted odds ratio 1.56, 95% CI 1.03–2.34), inconclusive evidence in Nigeria (adjusted odds ratio 1.17, 95% CI 0.95–1.45) and evidence of an inverse association in Trinidad and Tobago (adjusted odds ratio 0.66, 95% CI 0.44–0.97).
Conclusions
This study found no overall evidence of an association between witnessing or experiencing life events and psychotic disorder across three culturally and economically diverse countries. There was preliminary evidence that the association varies between settings.
In this analysis, we argue that the ‘treatment gap’ for common mental disorders often reflects lack of demand, arising because services fail to address the needs of disadvantaged communities. We propose a route forward for global mental health, with explicit focus on action on the socioeconomic determinants of psychological suffering.
The Diagnostic and Statistical Manual – 5th edition (DSM-5) definitions for Cluster A personality disorders have been valuable to the clinical, scientific, and consumer communities. However, they suffer from serious issues as scientific constructs and are difficult to precisely measure. These issues have constrained our ability to meaningfully comprehend their underlying biopsychosocial mechanisms and to develop cures and treatments. The authors consider three potential ways to improve the operationalization and measurement of Cluster A disorders. First, they discuss the viability of existing alternative diagnostic systems such as the DSM-5 alternative personality disorder model, the five-factor personality model, the Research Domain Criteria (RDoC), and the Hierarchical Taxonomy of Psychopathology (HiTop) systems. Second, they explore the utility of operationalizing Cluster A disorders within a broader spectrum of schizophrenia-related disorders. Lastly, they consider the viability of objectifying cluster A disorders symptoms and behaviors using various genotyping and phenotyping technologies (e.g., mobile devices). While each potential way has its strengths and weaknesses, collectively they may help account for the complex phenotypic heterogeneity associated with Cluster A disorders, provide objective markers of their severity, and facilitate individualized assessment, prevention, and treatment.
The dysfunctional cognitive and reasoning biases which underpin psychotic symptoms are likely to present prior to the onset of a diagnosable disorder and should therefore be detectable along the psychosis continuum in individuals with schizotypal traits. Two reasoning biases, Bias Against Disconfirmatory Evidence (BADE) and Jumping to Conclusions (JTC), describe how information is selected and weighed under conditions of uncertainty during decision making. It is likely that states such as elevated stress exacerbates JTC and BADE in individuals with high schizotypal traits vulnerable to displaying these information gathering styles. Therefore, we evaluated whether stress and schizotypy interacted to predict these reasoning biases using separate samples from the US (JTC) and England (BADE). Generally speaking, schizotypal traits and stress were not independently associated with dysfunctional reasoning biases. However, across both studies, the interaction between schizotypy traits and stress significantly predicted reasoning biases such that increased stress was associated with increased reasoning biases, but only for individuals low in schizotypal traits. These patterns were observed for positive schizotypal traits (in both samples), for negative traits (in the England sample only), but not for disorganization traits. For both samples, our findings suggest that the presence of states such as stress is associated with, though not necessarily dysfunctional, reasoning biases in individuals with low schizotypy. These reasoning biases seemed, in some ways, relatively immutable to stress in individuals endorsing high levels of positive schizotypal traits.
This paper reports on a benefit-cost analysis of a targeted intervention program, the YouthBuild USA Offender Project (YBOP), aimed at low-income, criminal offenders who are 16–24 years old. Using data on 388 participants, we find: (1) evidence of reduced recidivism and improved educational outcomes that exceed our expectations based on similar cohorts and (2) evidence consistent with a positive benefit-cost ratio, indicating that every dollar spent on the YBOP is estimated to produce a return on investment between $7.20 and $21.60, with benefits to society ranging between $174,000 and $281,000 per participant at a cost to society between $13,000 and $24,000.
Although neurocognitive deficits are an integral characteristic of schizophrenia, there is inconclusive evidence as to whether they manifest across the schizophrenia-spectrum. We conducted two studies and a meta-analysis comparing neurocognitive functioning between psychometrically defined schizotypy and control groups recruited from a college population. Study One compared groups on measures of specific and global neurocognition, and subjective and objective quality of life. Study Two examined working memory and subjective cognitive complaints. Across both studies, the schizotypy group showed notably decreased subjective (d = 1.52) and objective (d = 1.02) quality of life and greater subjective cognitive complaints (d = 1.88); however, neurocognition was normal across all measures (d's < .35). Our meta-analysis of 33 studies examining neurocognition in at-risk college students revealed between-group differences in the negligible effect size range for most domains. The schizotypy group demonstrated deficits of a small effect size for working memory and set-shifting abilities. Although at-risk individuals report relatively profound neurocognitive deficits and impoverished quality of life, neurocognitive functioning assessed behaviorally is largely intact. Our data suggest that traditionally defined neurocognitive deficits do not approximate the magnitude of subjective complaints associated with psychometrically defined schizotypy. (JINS, 2013, 19, 1–14)
Studies examining comparative outcomes of schizophrenia in high-incomecountries with those in low- and middle-income countries remain of interestto researchers and may be of value in understanding some environmentalfactors that influence the course and outcome of the disorder. The view thatthe disorder has a better outcome in low- and middle-income countriescompared with high-income countries, even though widespread and supported bya set of World Health Organization (WHO) studies, requires further testingand exploration. Unfortunately, although not insurmountable, the obstaclesfor such studies both in terms of implementation and interpretation areconsiderable.