Douglas Mental Health University Institute

Dementia frequently goes undetected in community settings, particularly among socially disadvantaged populations. Here, we estimated the prevalence of underdiagnosed dementia across diverse sociodemographic determinants of health in the Health and Aging Brain Study-Health Disparities (HABS-HD), a community-based cohort of adults recruited through community outreach in Fort Worth, Texas. We estimated age-specific probabilities of underdiagnosis using Poisson regression models with a log link, including age and sex as covariates. Robust (sandwich) variance estimators were used to obtain standard errors and 95% confidence intervals (CI). Group differences or trends for continuous measures were assessed using robust variance estimates. The prevalence of underdiagnosed dementia was higher among individuals without physician access (98.1% vs. 78.1%, p<.0001), non-English speakers (97.9% vs. 76.8%, p<.0001), and the uninsured (91.5% vs. 79.5%, p=.03). Black and Hispanic participants also showed higher prevalence (85.8% and 90.9%) compared to non-Hispanic White participants (64.9%; p=.02 and p=.002, respectively). Each additional year of education was associated with a 2.5% lower risk of underdiagnosis (p<.0001). No differences were observed by sex, marital status, income or social support. Our results highlight that several sociodemographic factors contribute to the likelihood of living with undiagnosed dementia.

International audience

Canada is advancing several reforms to strengthen primary health care. Although lesbian, gay, and bisexual (LGB) individuals experience a higher burden of some health conditions, they remain largely absent from these reforms, partly because of limited data. We assessed differences in primary care utilization between LGB and heterosexual individuals to address this gap. We used data from 91,172 heterosexual and 2,550 LGB participants in the 2015–2016 Canadian Community Health Survey. Guided by Andersen’s Behavioural Model of Health Services Use, we examined the association between primary care physician (PCP) consultation rates and our primary variables of interest: sex and sexuality. Estimates for heterosexual men, heterosexual women, gay and bisexual men (GBM), and lesbian and bisexual women (LBW) were obtained separately. Models were adjusted for additional covariates (predisposing, enabling, and need-based) identified in Andersen’s framework. Poisson regression was used for the main analysis, and results were compared with estimates from double-selection lasso models. GBM and LBW had higher PCP consultation rates over a 12-month period compared with heterosexual men. For every 100 PCP consultations among heterosexual men, there were an estimated 129 consultations (95% CI 112 to 148) among GBM and 123 consultations (95% CI 110 to 139) among LBW. In contrast, consultation rates for GBM and LBW were comparable with heterosexual women. Even after adjusting for several covariates, GBM and LBW had higher PCP consultation rates than heterosexual men. These findings suggest that PCP engagement among LGB adults differs from that of heterosexual men. The comparability with heterosexual women requires further investigation. More comprehensive data are needed to verify and clarify these findings to support equitable primary care planning.

Abstract Postmortem human brains stored in brain banks are important research resources to study the mechanisms underlying normal brain functions as well as various neurodegenerative disorders. Immunohistochemical (IHC) and histochemical (HC) staining have been used to examine human brains post-fixed in neutral-buffered formalin (NBF) for months, years, and even decades. As such, it is essential to establish the effects of prolonged post-fixation in NBF on both IHC and HC stains. Previously, we found that prolonged NBF post-fixation resulted in differential effects on IHC and HC staining on postmortem brains. In this study, we further examined the effects of prolonged post-fixation on IHC stains targeting 6 antigens and 2 HC stains of known biomarkers of cerebrovascular diseases in prefrontal cortex of human brains post-fixed for 1, 5, 10, 15, and 20 years. The IHC targets included microvasculature markers of the blood brain barrier (Collagen-IV and Claudin-5), a type III intermediate filament marker (Vimentin), an activated microglia marker (CD68), a biomarker for oligodendrocytic myelin proteolipid protein (PLP) and a marker for iron accumulation (Ferritin). The HC included Masson’s Trichrome Stain (MTS) and Bielschowsky silver stain (BSS). We found that staining intensities of Ferritin, Vimentin, Collagen-IV and BSS decreased with prolonged post-fixation, while no significant differences were observed in the staining intensity of other markers. Hence, these differential alterations should be taken into consideration when interpreting the results from processed tissues with prolonged post-fixation. We recommend performing IHC and HC staining for human brains with the same post-fixation times to offset any impact on downstream neuropathological analyses, as well as adding the post-fixation duration as a covariate in the analysis.

Biological psychiatry faces a significant epistemic challenge in identifying valid objects for mechanistic research. Both diagnostic constructs and individual symptoms are abstract symbols defined circularly within a closed hermeneutic system, creating a symbol grounding problem that hinders the discovery of biophysical substrates (biomarkers). I argue that progress requires an epistemological separation between the ungrounded symptoms such as delusions and hallucinations, which are co-constructed through personal and clinical interpretation from grounded signs that are directly observable features anchored in shared sensorimotor reality. I propose that a Minimal Grounding Set (MGS) can be recovered from the commonly used criteria for psychosis. This MGS, exemplified by disorganization and impoverishment, offers a privileged pathway for the neuroscientific inquiry of psychosis. In this case, (1) biological correlates will be most replicable for MGS than other symptoms; (2) MGS will serve as modular anchors in symptom networks; and (3) progress in precision medicine programs like Computational Psychiatry and quantitative psychopathology frameworks such as hierarchical taxonomy (HiTOP) will depend on explicitly separating MGS from ungrounded symptoms. This approach of sign-first psychiatry will provide a non-circular foundation to tether abstract constructs affiliated with psychosis to biological realities that have eluded us for long.

Abstract Numerous studies have shown that adults with depression have distinct oculomotor alterations during saccade tasks, but whether similar alterations occur in adolescents is largely unknown. The purpose of this study was to test if eye-tracking during a structured saccade task could distinguish a group of adolescents with depression from healthy controls. We hypothesized that, due to overlapping circuitry between depression pathology and the oculomotor system, adolescents with depression would show alterations in fixation, saccade, and pupil behaviour. 51 adolescents with depression and 66 age-matched healthy controls completed the Interleaved Pro- and Anti-Saccade Task (IPAST) and several self-reported questionnaires for psychiatric symptoms. Oculomotor outcomes included fixation acquisition, fixation breaks, correct rate, saccadic reaction time, rate of correct express-latency pro-saccades, rate of express- and regular-latency anti-saccade errors, baseline pupil size, as well as pupil constriction and dilation sizes following task instruction. In comparison to healthy controls, adolescents with depression displayed impairments acquiring fixation ( p &lt;.001), made more fixation breaks in pro- ( p =.023) and anti-saccade trials (p =.005), more anti-saccade errors ( p =.013), more express-latency saccades overall ( p s=.016), had a smaller pupil constriction in pro-saccade trials ( p =.047) and had a smaller pupil dilation in pro- ( p =.011) and anti-saccade trials ( p =.041). No differences were found for saccadic reaction time, rate of correct pro-saccades, rate of regular-latency anti-saccade errors, pupil constriction size during anti-saccade trials, or baseline pupil size. Patients had psychiatric comorbidities and were using psychotropic medication. While this reflected clinical reality, these factors may have influenced oculomotor behaviour. Adolescents with depression had altered fixation, saccade, and pupil behaviour during IPAST. Given that many cases of adolescent depression remain undetected, accessible and objective screening approaches are highly needed. This oculomotor phenotype may be used in the development of such a screening tool to detect those at risk.

Over the past few years, several fluid biomarker candidates have been proposed for frontotemporal dementia (FTD). We have previously identified CSF proteins that could separate individuals with genetic FTD from controls. However, it is unknown whether alterations in these CSF protein levels are associated with neurodegenerative processes. The aim of this study was to explore how these CSF biomarker candidates correlate with symptom severity as well as cortical and subcortical atrophy. The levels of fourteen proteins were measured in CSF from 202 individuals, 131 mutation carriers with mutations in C9orf72, GRN, or MAPT, and 71 controls, in a cross-sectional subset from the GENFI cohort. The association between the levels of these proteins and CDR plus NACC FTLD-NM sum-of-boxes, cortical thickness, and subcortical volumes were estimated in the mutation carriers. Elevated CSF levels of five out of fourteen proteins were associated with an increased CDR score in the mutation carriers. Additionally, elevated levels of three of these proteins, NEFM, PTPRN2 and SERPINA3, were associated with reduced cortical thickness and/or subcortical volume among all mutation carriers. Some mutation-specific associations were also observed, with SPP1 and CTSS being associated with CDR and atrophy only in MAPT mutation carriers, while NPTX2 was specific for GRN mutation carriers. As indicated by the association to brain atrophy, the proposed fluid biomarker candidates continue to show promise and additional studies will further elucidate their relationship to cortical atrophy in genetic FTD, and their potential as biomarkers for diagnosis, prognosis, and disease staging.

BACKGROUND:Patient reports are the standard when examining subjective cognitive decline (SCD). Recent research suggests that informant and clinician reports may also be associated with cognition. This study examined differences between patient, informant, and clinician definitions of SCD and their relationship to cognition.METHODS:Data from 4290 older adults (n=1690 normal controls, NC; n=840 mild cognitive impairment, MCI; n=1760 Alzheimer’s disease, AD) were examined from the National Alzheimer’s Coordinating Center. Linear models examined the relationships between SCD status using the three definitions and cognition at baseline and over time.RESULTS:In NC, informant and clinician SCD were associated with worse cognition at baseline, with patient and clinician SCD associated with worse cognition over time. All definitions were associated with worse cognition at baseline and over time in MCI and AD.DISCUSSION:Our findings suggest the importance of examining different SCD definitions, especially the inclusion of clinician SCD.