Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC‐CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence‐based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

A recent model for the role of chromium in insulin signaling requires that the oligopeptide low-molecular-weight chromium-binding substance (LMWCr) tightly bind four chromic ions before the oligopeptide obtains a conformation required for binding to the tyrosine kinase active site of the insulin receptor. To test this model, the chromium-binding constant of LMWCr was determined, and the ability of LMWCr to remove chromium from Cr2-transferrin and the nutritional supplement chromium picolinate, Cr(pic)3, was examined. These results are consistent with the model of the mode of action of LMWCr; a Hill study indicates the four chromic ions bind to apoLMWCr in a highly cooperative fashion (n =3.47) with a binding constant of 1.54x 10(21). Chromium is readily transferred from transferrin to apoLMWCr at near neutral pH. The results also suggest that reduction of the chromic center of Cr(pic)3 may be required for the supplement to release chromium; thus, release of chromium is related to a mechanism by which Cr(pic)3 may generate hydroxyl radicals in cells.

Risk, II.

The in vivo effects of administration of the synthetic, functional biomimetic [Cr3O(O2CCH2CH3)6(H2O)3]+ 1 and a naturally occurring, biologically active form of chromium, low-molecular-weight chromium-binding substance (LMWCr), to rats are described. Given that the complexes are proposed to function by interacting with insulin receptor, trapping it in its active conformation, in contrast to current chromium-containing nutrition supplements, which only serve as sources of absorbable chromium, changes in lipid and carbohydrate metabolism would be expected. After 12 weeks administration (20 micrograms/kg body mass), compound 1 results in 40% lower levels of blood plasma LDL cholesterol, 33% lower levels of total cholesterol, and significantly lower HDL cholesterol and triglyceride; these results are in stark contrast to those of administration of other forms of Cr(III) to rats, which have no effect on these parameters. LMWCr, in contrast to 1, has no effect as it probably is degraded in vivo or excreted. These results are interpreted in terms of the mechanism of chromium action in response to insulin and the activation of insulin receptor, and the potential for the rational design of chromium-containing therapeutics is discussed.

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Background The demand for specialized care in neurocognitive disorders greatly surpasses its availability. Patients have complex needs and specialists are scarce. As a result, there is a gap between the needs of patients and the capacity of health systems to address them. Expert systems help fill this gap working towards early and accurate phenotyping (description) of neurocognitive disorders to better identify and successfully allocate the limited resources. We developed the Cognitive Behavioral Score (CBS), a 51‐item structured self‐administered questionnaire and its caregiver counterpart (cCBS), conducting exploratory analyses on clinical feasibility and diagnostic utility, as well as association to neuropsychological performance. Method We enrolled 29 patients (age: 71.5±11.7; education: 9.6±2.8 years) with minor or major neurocognitive disorder (late age‐of‐onset Alzheimer’s disease with various degrees of vascular comorbidity; MMSE= 26.0±4.3) through the Sleep & Memory Center of the Neurological Institute of Athens. CBS and cCBS were completed by patients and/or their caregivers, covering cognitive, behavior, autonomic, and sleep symptom severity and duration. Patients underwent physical examinations, neuropsychological, biochemical and imaging testing. Statistical analyses were conducted using Pearson ρ or Kendall τ as appropriate, depending on data deviation from normality. Results Both CBS and cCBS were completed in‐clinic or at home within 5 minutes and provided a clinical overview of symptom progression. CBS and cCBS congruence total score was 0.36, certain domain‐specific sub scores were even better (0.46 – 0.67). Correlation to MMSE was better for cCBS (‐0.30), a feature reflective of the patient population. CBS and cCBS sub scores had varying degrees of correlation to domain‐specific neuropsychological tests, with historic symptoms of anomia having most and highest associations (≤ ‐0.76). Non‐cognitive symptoms were correlated to executive function, hinting to possible comorbid synucleinopathies or sleep deprivation. Conclusion The study results suggest that both CBS and cCBS have diagnostic utility for the clinician. They allow faster and more accurate description and identification of syndromic neurocognitive disorders. With better understanding, resources can be allocated in a more directed and better‐planned manner, helping low resource settings. Also these questionnaires minimize the time in history taking, allowing health professionals to dedicate more time to the patients for better and individualized care.

Background Cognitive Behavioral Sleep Medicine is a rapidly growing discipline that aims at the comprehensive evaluation and treatment of people with cognitive or sleep symptoms, established on the bidirectional relationship between sleep disorders and neurodegeneration. On this basis, we established a comprehensive evaluation protocol for deep phenotyping of cognitive‐sleep syndromes, and present first results on its feasibility and novel cognitive to sleep associations. Method We enrolled 29 patients (age: 71.5 ± 11.7; education: 9.6 ± 2.8 years) with minor or major neurocognitive disorder due to predicted Alzheimer’s disease with various degrees of vascular comorbidity (MMSE = 26.0 ± 4.3) through the Sleep & Memory Center of the Neurological Institute of Athens. All patients underwent comprehensive clinical evaluations, including cognitive (Cognitive Behavioral Symptoms [CBS] score) and sleep questionnaires (Insomnia Severity Index [ISI]; Epworth Sleepiness Scale [ESS]), biochemical, imaging, and within‐day neuropsychological testing, whereas six patients have further completed novel sleep‐mediated neuropsychological tests, actigraphy and polysomnography. Exploratory analyses using Pearson ρ or Kendall τ, accordingly, were performed to examine associations of subjective complaints and daily functioning to objective cognitive and sleep metrics. Result Non‐memory cognitive CBS scores were highly correlated to sleep CBS scores (ρ,τ ∼ 0.51 ‐ 0.71), as well as ISI (0.56) and ESS (0.54). Memory CBS complaints in contrast correlated more with subjective insomnia symptoms (0.72 to ISI) but not hypersomnia (‐0.15 to ESS). Additionally, the CBS total score was associated to sleep‐mediated 9‐item recall (0.81) and to sleep‐mediated phonemic fluency (‐0.55), an association also noted between ESS to sleep‐mediated 9‐item recall (0.71). Of note, subjective cognitive and sleep complaints were not well correlated to within‐day neuropsychological testing (e.g., 0.13 ‐ 0.36 to MMSE). Patients who underwent actigraphy and polysomnography tolerated all procedures, and those diagnosed with sleep apnea or insomnia are effectively pursuing CPAP treatment and Cognitive Behavioral Therapy for Insomnia respectively. Conclusion Comprehensive evaluation of sleep and cognitive symptoms is feasible in patients with neurocognitive disorders and allows for deep phenotyping of neurodegenerative diseases. Finally, sleep‐mediated cognitive tests seem to be more sensitive than within‐day tests in reflecting real‐life symptoms, highlighting their potential utility.