Examination of distributed learning on recent and remote memory using in-person and online experimental paradigms

Learning is crucial in everyday life. However, how much information we retain depends on the type and schedule of training. It has been widely acknowledged that spaced learning holds a distinct advantage over massed learning for cognitively healthy adults and should be considered an educational standard, particularly when consolidating long-term memory. Given that many experiments have been required to be conducted online as a result of social distancing regulations during the Covid-19 pandemic, we examined whether the spacing advantage could be replicated in an online setup. Two experiments were conducted to examine the effects of spacing across recent (24 hours) and remote (one-month) retention intervals using the Face-Name Pairs task either in-person (Experiment 1) or online (Experiment 2). The results of Experiment 1 suggest that the beneficial memory effects of spaced training are particularly observed with remote memory. The results of Experiment 2 suggest that although participants learn and recall better in an online setup compared to in-person, the spacing effects were not as robust and did not confer any real advantage. These results are discussed in terms of advantages and disadvantages of the two procedures and the implications for online studies.

Deterministic Constant-Amortized-RMR Abortable Mutex for CC and DSM

The abortable mutual exclusion problem, proposed by Scott and Scherer in response to the needs in real-time systems and databases, is a variant of mutual exclusion that allows processes to abort from their attempt to acquire the lock. Worst-case constant remote memory reference algorithms for mutual exclusion using hardware instructions such as Fetch&Add or Fetch&Store have long existed for both cache coherent (CC) and distributed shared memory multiprocessors, but no such algorithms are known for abortable mutual exclusion. Even relaxing the worst-case requirement to amortized, algorithms are only known for the CC model. In this article, we improve this state of the art by designing a deterministic algorithm that uses Fetch&Store to achieve amortized O (1) remote memory reference in both the CC and distributed shared memory models. Our algorithm supports Fast Abort (a process aborts within six steps of receiving the abort signal) and has the following additional desirable properties: it supports an arbitrary number of processes of arbitrary names, requires only O (1) space per process, and satisfies a novel fairness condition that we call Airline FCFS . Our algorithm is short with fewer than a dozen lines of code.

Predictive Factors for Conversion to Dementia in Individuals with Early-Onset Mild Cognitive Impairment

<b><i>Introduction:</i></b> There is little research on factors predicting conversion to dementia in early-onset mild cognitive impairment (eoMCI), a transitional stage between healthy ageing and dementia in individuals below the age of 65. We aimed to examine whether sociodemographic and clinical factors at initial presentation predicted dementia progression in a cohort of eoMCI patients attending a memory service, at a university teaching hospital in the UK. <b><i>Methods:</i></b> This is a retrospective case note study of individuals diagnosed with eoMCI between 2000 and 2013 at the Younger Person’s Memory Service (YPMS) in Leicestershire, England. Data collected at assessment included social factors, demographic characteristics, and medical and psychiatric history, as well as standardized cognitive assessment scores. Variables were analysed using χ² or independent sample <i>t</i> tests to identify associations. A Cox regression survival analysis was done to identify predictive factors for dementia conversion. An ROC analysis for total CAMCOG was used to investigate sensitivity and specificity for dementia converters versus non-converters. <b><i>Results:</i></b> Out of 531 subjects who attended YPMS, 65 patients were given a diagnosis of eoMCI (47.7% female; mean age 56.4 ± 7.54 years). Of these, 21 (32.3%) converted to dementia during their course within the service. Comparison between subgroups revealed a significant association between dementia conversion and higher years of education and lower MMSE and CAMCOG (total and subscale) scores at baseline. Smoking history, alcohol use, or medical history such as diabetes or heart disease were not associated with conversion. Cox regression survival analysis showed higher education in years and lower total CAMCOG scores were significant predictors for conversion. Lower scores on the recent memory, remote memory, learning memory, and executive function subscales of the CAMCOG were also significant predictors for conversion. ROC curve analysis for total CAMCOG demonstrated that the best detection of dementia converters can be achieved with a cutoff score of 90.5/107 (sensitivity of 76.2% and specificity of 68.2%). Area under the curve was 0.808 (95% CI: 0.697–0.920). <b><i>Conclusion:</i></b> More years in education and lower cognitive scores on CAMCOG at initial assessment are associated with progression to dementia from eoMCI. Further research is required to explore these predictive factors more.

Functional ultrasound imaging of recent and remote memory recall in the associative fear neural network in mice

Emotional learning and memory are affected in numerous psychiatric disorders. At a systems level, however, the underlying neural circuitry is not well defined. Rodent fear conditioning (FC) provides a translational model to study the networks underlying associative memory retrieval. In the current study, functional connectivity among regions related to the cue associative fear network were investigated using functional ultrasound (fUS), a novel imaging technique with great potential for detecting regional neural activity through cerebral blood flow. Behavioral fear expression and fUS imaging were performed one and thirty-one days after FC to assess recent and remote memory recall. Cue-evoked increases in functional connectivity were detected throughout the amygdala, with the lateral (LA) and central (CeA) amygdalar nuclei emerging as major hubs of connectivity, though CeA connectivity was reduced during remote recall. The hippocampus and sensory cortical regions displayed heightened connectivity with the LA during remote recall, whereas interconnectivity between the primary auditory cortex and temporal association areas was reduced. Subregions of the prefrontal cortex exhibited variable connectivity changes, where prelimbic connectivity with the amygdala was refined while specific connections between the infralimbic cortex and amygdalar subregions emerged during remote memory retrieval. Moreover, freezing behavior positively correlated with functional connectivity between hubs of the associative fear network, suggesting that emotional response intensity reflected the strength of the cue-evoked functional network. Overall, our data provide evidence of the functionality of fUS imaging to investigate the neural dynamics of memory encoding and retrieval, applicable in the development of innovative treatments for affective disorders.

P.015 What Happens to the Worried Well? – Follow-up of Subjective Cognitive Impairment

Background: Concern around perceived neurocognitive decline is increasing, leading to increased number of referrals and anxiety for patients. We aimed to explore the likelihood of the “worried well” experiencing neurocognitive decline. Methods: 166 “worried well” patients who attended the Rural and Remote Memory Clinic between 2004 and 2019 were included. Mini Mental Status Examination, Center for Epidemiologic Studies Depression Scale, and Functional Assessment Questionnaire scores were measured and compared at initial assessment and at 1-year follow-up. MMSE scores over time were assessed with a mean follow-up of 2.95 years (SD 2.87). Results: There was no statistically significant difference in MMSE, CESD, or FAQ scores between clinic day and one-year follow-up, and no consistent pattern of MMSE score over time. Of the 166 patients with SCI on initial assessment, nine were eventually given a neurological diagnosis. Conclusions: There is no pattern of neurologic decline observed in the “worried well”. Though the likelihood of a patient with SCI developing a neurological diagnosis is reassuringly low, (9/166), it is not irrelevant. This, along with the benefits of early diagnosis and treatment for dementia, leads us to believe that patients with SCI should still be seen in follow-up at least at the one-year mark.

The use of a computerised cognitive assessment to improve the efficiency of primary care referrals to memory services: Protocol for the ADePT study (Preprint)

BACKGROUND Existing primary care cognitive assessment tools are crude or time-consuming screening instruments which can only detect cognitive impairment when it is well established. Due to the COVID-19 pandemic, memory services have adapted to the new environment by moving to remote patient assessments to continue meeting service user demand. However, the remote use of cognitive assessments has been variable while there has been scant evaluation of the outcome of such a change in clinical practice. Emerging research in remote memory clinics has highlighted computerised cognitive tests, such as the Integrated Cognitive Assessment (ICA), as a prominent candidate for adoption in clinical practice both during the pandemic and for post-COVID implementation as part of healthcare innovation. OBJECTIVE We initiated the Accelerating Dementia Pathway Technologies (ADePT) study. The intention of conducting this study is to develop a real-world evidence basis to support the adoption of ICA as an inexpensive screening tool for the detection of cognitive impairment and improving the efficiency of the dementia care pathway. METHODS Patients who have been referred to a memory clinic from GPs are recruited. Participants complete the ICA either at home or in the clinic along with medical history and usability questionnaires. The GP referral and ICA outcome are compared with the specialist diagnosis obtained at the memory clinic. The clinical outcomes as well as NHS reference costing data will be used to assess the potential health economic benefits of the use of the ICA in the dementia diagnosis pathway. RESULTS The ADePT study was funded in January 2020 by Innovate UK (Project reference 105837). As of September 2021, 86 participants have been recruited in the study, with 23 participants also completing a retest visit. Initially the study was designed for in person visits at the memory clinic, however in light of the COVID-19 pandemic, the study was amended to allow remote as well as face-to-face visits. The study was also expanded from a single site to 4 sites in the United Kingdom. We expect results to be published by the second quarter of 2022. CONCLUSIONS The ADePT project aims at improving the efficiency of the dementia pathway at its very beginning and supports systems integration at the intersection between primary and secondary care. The introduction of a standardised, self-administered, digital assessment tool for the timely detection of neurodegeneration as part of a decision-support system that can signpost accordingly can reduce unnecessary referrals, reduce service backlog and assessment variability. CLINICALTRIAL ISRCTN Number: 16596456

Developmental emergence of persistent memory for contextual and auditory fear in mice

The ability to generate memories that persist throughout a lifetime (that is, memory persistence) emerges in early development across species. Although it has been shown that persistent fear memories emerge between late infancy and adolescence in mice, it is unclear exactly when this transition takes place, and whether two major fear conditioning tasks, contextual and auditory fear, share the same time line of developmental onset. Here, we compared the ontogeny of remote contextual and auditory fear in C57BL/6J mice across early life. Mice at postnatal day (P)15, 21, 25, 28, and 30 underwent either contextual or auditory fear training and were tested for fear retrieval 1 or 30 d later. We found that mice displayed 30-d memory for context– and tone–fear starting at P25. We did not find sex differences in the ontogeny of either type of fear memory. Furthermore, 30-d contextual fear retrieval led to an increase in the number of c-Fos positive cells in the prelimbic region of the prefrontal cortex only at an age in which the contextual fear memory was successfully retrieved. These data delineate a precise time line for the emergence of persistent contextual and auditory fear memories in mice and suggest that the prelimbic cortex is only recruited for remote memory recall upon the onset of memory persistence.