Clinical utility of Phototest via teleneuropsychology in Chilean rural older adults / Utilidade clínica do phototest via teleneuropsicologia em idosos rurais chilenos

ABSTRACT. The COVID-19 pandemic has shown the need for neuropsychological care for older adults with memory complaints in different contexts, including rural areas or areas with difficult access. Objective: This study aimed to analyze the clinical utility of the Phototest, through telemedicine, to identify mild cognitive impairment in rural older adults with memory complaints, during the COVID-19 pandemic. Methods: We performed a cross-sectional, case-control, and clinical utility comparison of brief cognitive tests (BCTs). The sample included 111 rural elderly people with mild cognitive impairment (MCI) and 130 healthy controls from the Los Lagos region, Chile. The instruments adopted were modified Mini-Mental State Examination (MMSEm) and adapted version of the Phototest (PT) for Chile. Results: To identify mild cognitive impairment, using a cutoff score of 27-28 points, the Phototest showed a sensitivity of 96.6% and a specificity of 81.8%; indicators superior to those of the MMSEm. Conclusions: The Phototest is more accurate than the MMSEm in identifying cognitive alterations in rural older adults with cognitive memory complaints through telemedicine. Therefore, its use in primary care is recommended in order to perform early detection of preclinical cognitive alterations in mild cognitive impairment or neurodegenerative diseases.

RESUMO. A pandemia de COVID-19 mostrou a necessidade de cuidados neuropsicológicos para adultos idosos com queixas de memória em diferentes contextos, incluindo áreas rurais ou áreas de difícil acesso. Objetivo: Analisar a utilidade clínica do Phototest, por meio da telemedicina, para identificar uma leve deficiência cognitiva em adultos idosos rurais com queixas de memória, durante a pandemia de COVID-19. Métodos: Realizamos uma comparação transversal, caso-controle e utilidade clínica dos testes cognitivos breves. Amostra: Cento e onze idosos rurais com deficiência cognitiva leve (DCL) e 130 controles saudáveis da região de Los Lagos, Chile. Instrumentos: Minimental modificado (MMSEm) e versão do teste fotográfico (PT) adaptada para o Chile. Resultados: Para identificar a DCL, usando pontuação de corte de 27-28 pontos, o Phototest mostrou sensibilidade de 96,6% e especificidade de 81,8%; indicadores superiores aos do MMSEm. Conclusões: O Phototest é mais preciso que o MMSEm para identificar, por meio da telemedicina, alterações cognitivas em adultos idosos rurais com queixas de memória cognitiva. Sendo assim, seu uso na atenção primária é recomendado para realizar a detecção precoce de alterações cognitivas pré-clínicas em DCL ou doenças neurodegenerativas.

Clinical utility of Phototest via teleneuropsychology in Chilean rural older adults.

The COVID-19 pandemic has shown the need for neuropsychological care for older adults with memory complaints in different contexts, including rural areas or areas with difficult access. Objective: This study aimed to analyze the clinical utility of the Phototest, through telemedicine, to identify mild cognitive impairment in rural older adults with memory complaints, during the COVID-19 pandemic. Methods: We performed a cross-sectional, case-control, and clinical utility comparison of brief cognitive tests (BCTs). The sample included 111 rural elderly people with mild cognitive impairment (MCI) and 130 healthy controls from the Los Lagos region, Chile. The instruments adopted were modified Mini-Mental State Examination (MMSEm) and adapted version of the Phototest (PT) for Chile. Results: To identify mild cognitive impairment, using a cutoff score of 27-28 points, the Phototest showed a sensitivity of 96.6% and a specificity of 81.8%; indicators superior to those of the MMSEm. Conclusions: The Phototest is more accurate than the MMSEm in identifying cognitive alterations in rural older adults with cognitive memory complaints through telemedicine. Therefore, its use in primary care is recommended in order to perform early detection of preclinical cognitive alterations in mild cognitive impairment or neurodegenerative diseases.

A pandemia de COVID-19 mostrou a necessidade de cuidados neuropsicológicos para adultos idosos com queixas de memória em diferentes contextos, incluindo áreas rurais ou áreas de difícil acesso. Objetivo: Analisar a utilidade clínica do Phototest, por meio da telemedicina, para identificar uma leve deficiência cognitiva em adultos idosos rurais com queixas de memória, durante a pandemia de COVID-19. Métodos: Realizamos uma comparação transversal, caso-controle e utilidade clínica dos testes cognitivos breves. Amostra: Cento e onze idosos rurais com deficiência cognitiva leve (DCL) e 130 controles saudáveis da região de Los Lagos, Chile. Instrumentos: Minimental modificado (MMSEm) e versão do teste fotográfico (PT) adaptada para o Chile. Resultados: Para identificar a DCL, usando pontuação de corte de 27-28 pontos, o Phototest mostrou sensibilidade de 96,6% e especificidade de 81,8%; indicadores superiores aos do MMSEm. Conclusões: O Phototest é mais preciso que o MMSEm para identificar, por meio da telemedicina, alterações cognitivas em adultos idosos rurais com queixas de memória cognitiva. Sendo assim, seu uso na atenção primária é recomendado para realizar a detecção precoce de alterações cognitivas pré-clínicas em DCL ou doenças neurodegenerativas.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Neurological Entity?

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disorder of unknown physiopathology with multisystemic repercussions, framed in ICD-11 under the heading of neurology (8E49). There is no specific test to support its clinical diagnosis. Our objective is to review the evidence in neuroimaging and dysautonomia evaluation in order to support the neurological involvement and to find biomarkers serving to identify and/or monitor the pathology. The symptoms typically appear acutely, although they can develop progressively over years; an essential trait for diagnosis is "central" fatigue together with physical and/or mental exhaustion after a small effort. Neuroimaging reveals various morphological, connectivity, metabolic, and functional alterations of low specificity, which can serve to complement the neurological study of the patient. The COMPASS-31 questionnaire is a useful tool to triage patients under suspect of dysautonomia, at which point they may be redirected for deeper evaluation. Recently, alterations in heart rate variability, the Valsalva maneuver, and the tilt table test, together with the presence of serum autoantibodies against adrenergic, cholinergic, and serotonin receptors were shown in a subgroup of patients. This approach provides a way to identify patient phenotypes. Broader studies are needed to establish the level of sensitivity and specificity necessary for their validation. Neuroimaging contributes scarcely to the diagnosis, and this depends on the identification of specific changes. On the other hand, dysautonomia studies, carried out in specialized units, are highly promising in order to support the diagnosis and to identify potential biomarkers. ME/CFS orients towards a functional pathology that mainly involves the autonomic nervous system, although not exclusively.

Effects of Cycloleucine in the Nucleus Accumbens Septi on the Elevated plus Maze Test in Rats.

INTRODUCTION: In recent years, an important number of studies have emphasized the psychopharmacological actions of cycloleucine (1-aminocyclopentanecarboxylic acid) acting on the NR1 subunit (glycine allosteric site) of NMDA (N-methyl-D-aspartic acid) receptor. We studied the effects of its injection in an anxiety test. METHODS: The elevated plus maze test was used. Male rats bilaterally cannulated into the nucleus accumbens septi (NAS) were employed. Rats were divided into 5 groups that received either 1 µL injections of saline or cycloleucine (0.5, 1, 2, or 4 µg) 15 min before testing. RESULTS: Time spent in the open arm was significantly increased by cycloleucine treatment with all doses (1 and 2 µg, p < 0.05; 0.5 and 4 µg, p < 0.01), like number of extreme arrivals (0.5 and 1 µg, p < 0.05; 2 µg, p < 0.01; and 4 µg, p < 0.001). Open arm entries were increased by the highest dose only (4 µg, p < 0.01). DISCUSSION/CONCLUSION: Present results show no difference between all doses in the time spent in the open arm, suggesting an indirect, noncompetitive action of the drug. The increase in extreme arrivals and open arm entries suggests a dose influence in these parameters. We conclude that cycloleucine influence on the NMDA receptors within NAS leads to anxiolytic-like effects and behavioral disinhibition, which once more confirms the involvement of NAS in anxiety processing.

Erratum to: Short-Term Exposure to Enriched Environment in Adult Rats Restores MK-801-Induced Cognitive Deficits and GABAergic Interneuron Immunoreactivity Loss.

The original version of this article unfortunately contained a mistake. The name of author was changed from "Pascual Gargiulo" to "Pascual Ángel Gargiulo.

Short-Term Exposure to Enriched Environment in Adult Rats Restores MK-801-Induced Cognitive Deficits and GABAergic Interneuron Immunoreactivity Loss.

Perinatal injections of N-methyl-D-aspartate (NMDA) receptor antagonist in rodents emulate some cognitive impairments and neurochemical alterations, such as decreased GABAergic (gamma aminobutyric acid) interneuron immunoreactivity, also found in schizophrenia. These features are pervasive, and developing neuroprotective or neurorestorative strategies is of special interest. In this work, we aimed to investigate if a short exposure to enriched environment (EE) in early adulthood (P55-P73) was an effective strategy to improve cognitive dysfunction and to restore interneuron expression in medial prefrontal cortex (mPFC) and hippocampus (HPC). For that purpose, we administered MK-801 intraperitoneally to Long Evans rats from postnatal days 10 to 20. Twenty-four hours after the last injection, MK-801 produced a transient decrease in spontaneous motor activity and exploration, but those abnormalities were absent at P24 and P55. The open field test on P73 manifested that EE reduced anxiety-like behavior. In addition, MK-801-treated rats showed cognitive impairment in novel object recognition test that was reversed by EE. We quantified different interneuron populations based on their calcium-binding protein expression (parvalbumin, calretinin, and calbindin), glutamic acid decarboxylase 67, and neuronal nuclei-positive cells by means of unbiased stereology and found that EE enhanced interneuron immunoreactivity up to normal values in MK-801-treated rats. Our results demonstrate that a timely intervention with EE is a powerful tool to reverse long-lasting changes in cognition and neurochemical markers of interneurons in an animal model of schizophrenia.

Glutamate and modeling of schizophrenia symptoms: review of our findings: 1990-2014.

In the early 90s, we studied the role of perception disturbances in schizophrenia in our first clinical approaches, using the Bender test in schizophrenic patients. Results were clear, showing a shape discrimination failure. Following this initial results, we reproduced nuclear symptoms of schizophrenia in animal models, showing that perceptual disturbances, acquisition disturbances, decrease in affective levels and working memory disturbances can be induced by specific N-methyl-D-aspartic acid (NMDA) glutamatergic blockade within the nucleus accumbens septi (NAS). We studied also another glutamatergic and dopaminergic drugs, finding that a decrease in glutamatergic transmission within NAS led to cognitive disturbances and affective flattening. An increase in glutamatergic transmission fully enhances cognition in the tasks used. Dopaminergic D-2 antagonists partially improved cognition. Our results link the proposed corticostriatal dysfunction with the thalamocortical disturbances underlying perceptual problems, but also influencing affective levels and cognitive variables. According to our translational findings, core schizophrenia symptoms may be translationally reproduced antagonizing NMDA receptors within NAS, and improved blocking the glutamate auto-receptor. Dopaminergic transmission appears to have a role in therapeutic but not in the early pathophysiology of schizophrenia.

Alpha and beta noradrenergic mediation of NMDA glutamatergic effects on lordosis behaviour and plasmatic LH concentrations in the primed female rat.

In previous studies we have found that blockade of NMDA (N-Methyl-D-Aspartic-Acid)-type glutamatergic receptor with intracerebroventricular (ICV) selective drugs induces an inhibition of lordosis in ovariectomized (OVX) estrogen primed rats receiving progesterone or luteinizing hormone releasing hormone (LHRH). By the opposite way, stimulation with NMDA in OVX estrogen primed rats induced a significant increase of lordosis. In the present study the action of an alpha1-noradrenergic antagonist, HEAT (BE 2254/2-beta-4-Hydroxyphenyl-Ethyl-Aminomethyl-1-Tetralone), and Metoprolol, a beta-noradrenergic antagonist, were studied injecting them ICV previously to NMDA administration in treated OVX estrogen primed rats. In experiment 1, the enhancing effect on lordosis induced by NMDA at high dose (1 microg) was abolished by HEAT administration (P < 0.001 for 3 and 6 microg), and the LH plasma levels were decreased only with the higher dose (P < 0.05), suggesting that behavioral effects are quite more sensitive to the alpha-blockade than hormonal effects. In experiment 2, enhancing effects on lordosis behavior were not observed with neither the NMDA at low dose (0.5 microg) nor the metoprolol alone (5.71 microg), but a synergism was observed when both were simultaneously administered (P < 0.001). The LH plasma levels were increased by Metoprolol alone (P < 0.05), and powered by the combination with NMDA at low dose (P < 0.01 vs. SAL and NMDA alone); no differences were observed with Metoprolol. LH increase was observed with Metoprolol even without behavioural modifications. These findings strongly suggest that facilitatory and inhibitory effects of NMDA in this model are mediated by alpha- and beta-adrenergic transmission in both, behavioral and hormonal effects.