Objectives: Dementia assessment includes cognitive and behavioral testing with informant verification. Conventional testing is resource-intensive, with uneven access. Online unsupervised assessments could reduce barriers to risk assessment. The aim of this study was to assess the relationship between informant-rated behavioral changes and participant-completed neuropsychological test performance in older adults, both measured remotely via an online unsupervised platform, the Brain Health Registry (BHR). Design: Observational cohort study. Setting: Community-dwelling older adults participating in the online BHR. Informant reports were obtained using the BHR Study Partner Portal. Participants: The final sample included 499 participant–informant dyads. Measurements: Participants completed online unsupervised neuropsychological assessment including Forward Memory Span, Reverse Memory Span, Trail Making B, and Go/No-Go tests. Informants completed the Mild Behavioral Impairment Checklist (MBI-C) via the BHR Study Partner portal. Cognitive performance was evaluated in MBI+/− individuals, as was the association between cognitive scores and MBI symptom severity. Results: Mean age of the 499 participants was 67, of which 308/499 were females (61%). MBI + status was associated with significantly lower memory and executive function test scores, measured using Forward and Reverse Memory Span, Trail Making Errors and Trail Making Speed. Further, significant associations were found between poorer objectively measured cognitive performance, in the domains of memory and executive function, and MBI symptom severity. Conclusion: These findings support the feasibility of remote, informant-reported behavioral assessment utilizing the MBI-C, supporting its validity by demonstrating a relationship to online unsupervised neuropsychological test performance, using a previously validated platform capable of assessing early dementia risk markers.

Background Non‐cognitive markers may be utilized in dementia risk assessments. Mild behavioural impairment (MBI) is a validated neurobehavioural syndrome developed by an Alzheimer’s Association‐ISTAART working group including the following criteria: 1) later life emergent and persistent neuropsychiatric symptoms; 2) representing a change from longstanding personality or patterns of behaviour; 3) not better accounted for by psychiatric conditions or life stressors. MBI as an at‐risk state for cognitive decline and dementia and may be the earliest manifestations of disease for some. We investigated whether MBI, measured with the MBI checklist, was associated with cognitive changes in older adults in the Brain Health Registry (BHR). Methods We analyzed data from 5225 participants in BHR. Participants were included if they completed Lumosity cognitive tests (memory span, reverse memory span, trailmaking, go‐no‐go) and an informant‐rated MBI‐C. We excluded participants with major neurological, psychiatric or developmental disorders. Using cutpoints to dichotomize MBI+ and MBI‐ participants (MBI‐C > 5, 6, 7), univariate ANOVA was used to determine whether people with MBI also showed impairment in cognitive test performance. ANOVAs covaried for age, sex, education, and time between test administration and MBI‐C completion. All assessments were completed remotely, using the BHR online registry. Results The final sample included 802 participants with a mean age of 66.97(SD 10.71), of which 515/802 were females (64.21%). The number and percent of MBI‐C+ participants was 62 (7.7%), 53 (6.6%), and 48 (6.0%) at cutpoints of MBI‐C >5, >6, and >7 respectively. MBI+ participants had significantly poorer memory span, poorer reverse memory span, longer trail‐making completion time, and more trail‐making errors (see Table 1 for statistical reporting). A significantly greater number of men were classified as MBI+ at all 3 cutpoints (p< 0.001). Conclusions In a large cohort of older adults in BHR, MBI assessed remotely and unsupervised using an online interface, was associated with poorer cognition in the domains of memory and executive function compared to those without MBI. Utilizing the MBI‐C in case finding may be a simple, efficient, and scalable way to detect individuals with subtle cognitive changes, for further assessment and workup, or potential inclusion in clinical trials.

In patients suffering from post-traumatic stress disorder (PTSD), fear evoked by trauma-related memories lasts long past the traumatic event and it is often complicated by general anxiety and depressed mood. This poses a treatment challenge, as drugs beneficial for some symptoms might exacerbate others. For example, in preclinical studies, antagonists of the NR2B subunit of N-methyl-d-aspartate receptors and activators of cAMP-dependent protein kinase (PKA) act as potent antidepressants and anxiolytics, but they block fear extinction. Using mice, we attempted to overcome this problem by interfering with individual NR2B and PKA signaling complexes organized by scaffolding proteins. We infused cell-permeable Tat peptides that displaced either NR2B from receptor for activated C kinase 1 (RACK1), or PKA from A-kinase anchor proteins (AKAPs) or microtubule-associated proteins (MAPs). The infusions were targeted to the retrosplenial cortex, an area involved in both fear extinction of remotely acquired memories and in mood regulation. Tat-RACK1 and Tat-AKAP enhanced fear extinction, all peptides reduced anxiety and none affected baseline depression-like behavior. However, disruption of PKA complexes distinctively interfered with the rapid antidepressant actions of the N-methyl-D-aspartate receptors antagonist MK-801 in that Tat-MAP2 blocked, whereas Tat-AKAP completely inverted the effect of MK-801 from antidepressant to depressant. These effects were unrelated to the MK-801-induced changes of brain-derived neurotrophic factor messenger RNA levels. Together, the findings suggest that NR2B–RACK1 complexes specifically contribute to fear extinction, and may provide a target for the treatment of PTSD. AKAP-PKA, on the other hand, appears to modulate fear extinction and antidepressant responses in opposite directions.

INTRODUCTION: Dementia assessment includes cognitive and behavioral testing with informant validation. Conventional testing is resource intensive, with uneven access. Online unsupervised assessments could reduce barriers to risk assessment. We interrogated the relationship between informant-rated behavioral changes and neuropsychological test performance in older adults in the Brain Health Registry. METHODS: Participants completed online unsupervised cognitive tests, and informants completed the Mild Behavioral Impairment Checklist via a Study Partner portal. Cognitive performance was evaluated in MBI+/- individuals, as was the association between cognitive scores and MBI symptom severity. RESULTS: Mean age of the 499 participants was 67, 61% of which were female. MBI+ participants had lower working memory and executive function test scores. Lower cognitive test scores associated with greater MBI burden. DISCUSSION: Our findings support the feasibility of remote, informant-reported behavioral assessment and support its validity by demonstrating a relationship to cognitive test performance using online unsupervised assessments for dementia risk assessment.