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Background: The Cognitive Domains and Functional Assessment Questionnaire (CDFAQ) assesses cognitive domains and functional decline based on the DSM‐5 criteria for Neurocognitive Disorders. It has two versions, one for the patient (CDFAQ‐PV) and another for the informant (CDFAQ‐IV) assessing: Complex Attention (CA), Executive Functions (EF), Learning and Memory (LM), Language (L), Perceptual‐Motor Domain (PM) and Social Cognition. Recently, the CDFAQ was translated and adapted to English. Method: To describe the performance of the CDFAQ‐PV and CDFAQ‐IV assessing Brazilian older adults compared with the Informant Questionnaire on Cognitive Decline in the Elderly Long Version – IQCODE‐LV. This study was approved by the ethical committee of the UFMG and the CDFAQ was applied to 132 subjects in the University Hospital. The CDFAQ‐PV was applied to 66 older adults and the CDFAQ‐IV, as well as the IQCODE‐LV, to their 66 respective informants. Non‐parametric correlation with IQCODE‐LV and accuracy assessment by Receiver Operating Characteristic (ROC) with cutoff for dementia were performed. Result: The median age of the patients was 70.5 years (IQR = 13.5) and 5 years of schooling (IQR = 7), while the informants had a median age of 55 years (IQR = 24.5) and 12 years of schooling (IQR = 8). The CDFAQ‐IV showed a strong positive correlation (Rho:0.708, p<0.001) to IQCODE‐LV. Interestingly, the LM Domain had an even higher positive correlation (Rho:0.758, p<0.001), while the CDFAQ‐PV had moderate (Rho:0.405, p = 0.001) and its LM Domain had a weak (Rho:0.348, p = 0.004) positive correlations. The CDFAQ‐IV had a good area under the curve (0.871) as well as its LM (0.861), L (0.832), EF (0.854) Domains, while SC, PM were considered only fair. The cutoff values were assessed by Youden's J statistics: CDFAQ‐IV Total score ≥66.5 (SE:88.9%; SP:89.6%) and the LM Domain score ≥11,5 (SE:88.9; SP:77.1%) had the best performances. Conclusion: The strong correlation of the CDFAQ‐IV and its LM Domain to the IQCODE‐LV, as well as the good area under the curve, points a good accuracy for assessing neurocognitive disorders when applied to their informants. Nevertheless, this is still preliminary data, and more assessments in different scenarios, as well as, comparing with objective cognitive assessment is still needed. [ABSTRACT FROM AUTHOR]

Background: The immune system activation observed in Alzheimer's disease (AD) pathology contributes to its pathogenesis. It is proposed that ongoing interactions between β‐amyloid plaques, Tau protein, and neuroinflammatory mediators such as cytokines contribute to the maintenance of the inflammatory state in the brain. The aim was to evaluate whether cytokine profiles can predict variations in Aβ42, pTau, and pTau/Aβ42 cerebrospinal fluid (CSF) levels in older adults with and without objective cognitive impairment. Methods: Eighty older adults were recruited, with a clinical diagnosis of AD dementia (36), with Mild Cognitive Impairment (MCI) (24), and without objective cognitive impairment (20). CSF levels of Aβ42, pTau, and 27 cytokines were assessed by the Luminex xMAP technique. Significant associations between Aβ42, p‐Tau, and p‐Tau/Aβ42 CSF levels and cytokines were explored in multiple linear regression analyses adjusted for age, education, and APOE ε4 carrier status. Results: We found that Granulocyte and Macrophage colony‐stimulating factors (GM‐CSF) (β = ‐.375; p =.010) and IL‐6 (β = ‐.370; p =.014) had a negative significant association with Aβ42, while IL‐8 (β =.452; p =.002) and IL‐4 (β =.488; p =.001) had positive significant association and higher magnitude of effect on Aβ42. For pTau, age (β =.240; p =.029), IL‐2 (β =.314; p =.012) and ε4 allele (β = 0.349; p =.002) had a positive significant association. The variable with the greatest magnitude of the effect was the presence of the ε4 allele. For the p‐Tau/Aβ42 ratio, G‐CSF (β =.423; p =.003) and GM‐CSF (β =.317; p =.019) had a significant positive association, while for IL‐8 (β = ‐.554; p =.001) and IL‐12 (β = ‐.334; p =.019) the association was significantly negative. IL‐8 had the greatest magnitude of effect on p‐Tau/Aβ42 ratio values. Conclusion: The higher levels of IL‐4 and the IL‐8 associated to a higher Aβ42 suggest their role at the beginning of the disease. On the other hand, the lower level of IL‐8 associated with a higher p‐Tau/Aβ42 suggests its inactivation as the disease progresses. Conversely, the higher levels of GM‐CSF associated with higher p‐Tau/Aβ42 suggests a more robust recruitment of the immune cell system at later stages. Reference: Aksnes, M., et al., (2021). Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer's disease. Translational Neurodegeneration. [ABSTRACT FROM AUTHOR]

About 30% of patients diagnosed with major depressive disorder fail with the mainstream pharmacological treatment. Patients who do not achieve clinical remission of symptoms, even with two different antidepressants, are classified with treatment-resistant depression (TDR). This condition imposes an additional burden with increased Disability Adjusted Life Years. Therefore, complementary treatments, such as neuromodulation, are necessary. The transcranial focused ultrasound (tFUS) has emerged in the past few years as a reliable method for non-invasive neuromodulation in humans and may help treat TRD. This study aims to propose a research protocol for a non-inferiority randomized clinical trial of TDR with tFUS. Patients with documented TRD will be screened upon entering the TRD outpatient clinic at UFMG (Brazil). One hundred patients without a clinical history of other psychiatric illness, anatomical abnormalities on magnetic resonance imaging (MRI), or treatment with electroconvulsive therapy will be invited to participate. Patients will be randomized (1:1) into two groups: 1) treatment with a previously established protocol of transcranial magnetic stimulation; and 2) treatment with a similar protocol using the stimulation. Besides regular consultations in the outpatient clinic, both groups will attend 7 protocolled spaced days of brain stimulation targeted at the left dorsolateral prefrontal cortex. They will also be submitted to 4 sessions of image studies (2 MRIs, 2 positron-emission tomography), 3 of neuropsychological assessments (at baseline, 1 week and 2 months after treatment), the Montgomery-Åsberg Depression Rating Scale to analyze the severity of depressive symptoms. This clinical trial intends to verify the safety and clinical efficacy of tFUS stimulation of the dorsolateral prefrontal cortex of patients with TRD, compared with a previously established neuromodulation method. [ABSTRACT FROM AUTHOR]

Background: The Cognitive Domains and Functional Assessment Questionnaire (QACDF) assesses cognitive and functional decline based on the DSM‐5 criteria for Neurocognitive Disorders¹. The QACDF has two versions, one for the patient and another for the informant. It is composed of 30 items, each assessed by a likert scale. This questionnaire has appropriate semantic characteristics for the Brazilian older adult population. Method: The objective of this study was to translate, adapt and assess the semantic, idiomatic, experiential and conceptual equivalence of the QACDF. Firstly, the QADCF original version in Portuguese was translated to English by two Bilingual translators, a non‐specialist linguist and a specialist in the field. After this, the two translators (T1 and T2) together with a mediator translator synthesized the translations in a common version (T3). Then, the T3 version was back‐translated into Portuguese by a Bilingual translator, blind to the original version². The three versions (original, translated and back‐translated) were assessed by a committee of specialists. The committee was composed of the initial translators, an English native speaker, an expert in the methodology and the main researchers. Result: The QACDF Items were adjusted to conceive equivalent expressions for the target language, as well as to assess cognitive domains and the functionality of daily living of English speakers. Semantic, idiomatic, experiential and conceptual equivalence were debated by the committee until consensus was reached. Conclusion: The translation of the instrument followed the proposed methodology by Beaton et col. However, while the Brazilian Portuguese versions have been assessed by two pilot studies, pilot studies are still needed to further adjust the questionnaires for English speakers. [ABSTRACT FROM AUTHOR]

Obesity has reached epidemic proportions worldwide, affecting life quality and span. Susceptibility to obesity is partly mediated by genetic differences. Indeed, several genes from the clock gene family have already been shown to be intimately associated with obesity in diverse ethnic groups. In the present study, an association between BMI and the rs707467 , rs228697 and rs228729 PER3 (Period Circadian Clock 3) polymorphisms in subjects with class II (BMI ≥ 35.0–39.9 kg/m2) and class III obesity (>40 kg/m2, extreme obesity) were carried out using TaqMan real-time PCR. Overall, 259 Brazilian adults were genotyped, of whom 122 had class II or III obesity (BMI ≥ 35.0 kg/m2) and 137 were controls having normal weight (BMI > 18.5 and <24.9 kg/m2). PER3 tag SNP (rs228729) shows a significant association with extreme obesity (1000 permutation p = 0.03 and p = 0.04), for genotype and allele frequency respectively) and a haplotype among the three assessed SNPs (alleles G/T/A, rs228697 , rs228729 , and rs707467 , respectively, 1000 permutation p = 0.03) was significantly more prevalent in the group with obesity. This exploratory association study suggests that PER3 rs228729 may be associated with extreme obesity in Brazilian adults, however, replication is needed. [ABSTRACT FROM AUTHOR]

Background: The neuroinflammation process is one of the main pathological features of Alzheimer's disease (AD). In the course of AD, the deposits of β‐amyloid plaques and neurofibrillary tangles lead to over‐activation of the microglia, resulting in increased production of pro‐inflammatory and anti‐inflammatory cytokines that may contribute to neuronal dysfunction and cell death. Currently, several efforts have been made to discover the role of cytokines in AD's pathogenesis and the relationship between these inflammatory factors and the presence of AD's main biological markers (1). The present study aimed to determine the quantitative correlation between cytokines, β‐amyloid, and Tau proteins and the cognitive status of the participants. Method: CSF was collected by lumbar puncture from 80 older individuals with clinically defined AD (n=36), with amnestic mild cognitive impairment (aMCI) (n=24), and without objective cognitive impairment (n=20). CSF levels of β‐amyloid and p‐tau and t‐Tau and 27 cytokines were determined using the Luminex xMAP technique. Correlations were made between the cytokines, the β‐amyloid and Tau proteins levels, and the Mini‐Mental State test (MEEM). Result: considering all individuals, there was a significant positive correlation between Aβ42, IL‐4 and IL‐8; p‐Tau positively correlated with G‐CSF and GM‐CSF and finally p‐Tau/Aβ42 negatively correlated with IL8. The MEEM was correlated negatively with Eotaxin, IL‐6 and IL‐15. Focusing only in the AD group, there was a positive correlation for Aβ42 with IL‐4, IL‐8 and negatively with IL‐17; t‐Tau correlated negatively with IL‐1ra and IL‐5; p‐Tau/Aβ42 positively correlated with IL‐17 and negatively with IL‐8 and IP10. The MEEM showed a positive correlation with IL‐4. In the control group, Aβ42 and VEGF had a negative correlation; p‐Tau negatively correlated with TNF‐α; p‐Tau/Aβ42 were correlated positively with GM‐CSF, IL‐1β and IL‐6. The MEEM did not present any correlation. Between the aMCI group, t‐Tau was correlated positively with PDGF‐BB, and the MEEM was correlated negatively with Eotaxin. Conclusion: Changes in the neuroinflammatory profile are more prominent in AD patients compared to individuals without subjective cognitive impairment and those with aMCI. [ABSTRACT FROM AUTHOR]

Background: The incidence and prevalence of dementia are increasing, mainly in low‐ and middle‐income countries. Alzheimer's disease (AD) accounts for the majority of cases. Thus, cost‐effective techniques with lower cost are necessary for scaling up the number of tested individuals in these countries for research and clinical use. Luminex (Millipore xMap®) is a semi‐automated test that can analyze CSF biomarkers with a cost per sample of one fourth of ELISA's kits. Method: We performed a cross‐sectional, case‐control study. After consent, 35 older adults were submitted to clinical and neuropsychological assessment, and then to a lumbar puncture. Based on clinical and neuropsychological assessment, seven patients had a diagnosis of AD's dementia (McKhann criteria), 17 of amnestic mild cognitive impairment (MCI) (DSM‐5 criteria) and 11 without objective cognitive impairment. CSF biomarkers concentrations were measured by INNOTEST® (ELISA) and Millipore xMap®. Both techniques were compared and the accuracy of the latter was assessed. Result: Millipore xMap® measurements showed a robust accuracy for all biomarkers, with AUC of 0.808 for t‐Tau, 0.935 for p‐Tau and 0.952 for Aβ42 compared to ELISA as the reference test. The Aβ42 showed a great sensibility (100%) and the ratio p‐tau/Aβ42 a good specificity (0,944). So, we propose a stepwise approach for the diagnosis of AD based on CSF biomarkers. A patient with a cognitive assessment suggestive of AD (MCI or initial dementia) could be initially assessed for CSF biomarkers with a more affordable test, such as Luminex. If there is a need of a confirmation due low pretest probability or the need of a more specific test for a high‐cost treatment, researchers and clinicians could order an ELISA test in the same CSF sample or additional molecular neuroimaging techniques. For patients with a high pretest probability, Luminex has excellent accuracy and can define biological diagnosis. Conclusion: The use of Millipore xMap® as the first step in a stepwise approach for the assessment of suspected AD in middle‐ and low‐income countries cases is promising, considering its accuracy and lower cost per sample. Still, the implementation of the proposed approach in this study should be replicated in larger and different samples. [ABSTRACT FROM AUTHOR]

Background: Post Covid‐19 syndrome is recognized as the maintenance of disease symptoms for weeks to months after the disease has healed. It is suspected that the involvement of the ACE enzyme and IL‐6 may trigger an increased risk of dementia. Method: This is a cohort study that is evaluating over 12 months the functional status and cognition of elderly people after hospital discharge. One group is composed of elderly people admitted to the hospital for Covid‐19 and the other group is composed of elderly people hospitalized for other clinical reasons. The groups are evaluated with The Mattis (DRS), AD8, IQCODE, ADCS‐ADL, PCL‐C, GDS‐15, FIM, COPM, CFS, FSS, mMRC and SARC‐calf. We will describe the preliminary results of the first 15 patients included in the COVID‐19 group on functional status, cognition, mood and quality of life. Results: Fifteen patients with COVID‐19 were evaluated three months after hospital discharge. One was excluded due to previous mental disorder and another due to a request to be excluded from the study. We found a mean age of 67.7 ± 7.15 years, schooling 8.7 ± 4.7 years, 61.5% female, Charlson Comorbidity Index 1.9 ± 1.4, 69.2% with smoking history had incomplete vaccine protection for COVID‐19. Considering cognition, 15.4% of the sample had no impairment, 53.9% had mild cognitive impairment (MCI) (30.8% amnestic MCI and 23.1% non‐amnesic MCI) and 30.8% had dementia. 23.1% declared their health status and quality of life as fair or poor. Median CFS was 5 (3‐5), mean GDS‐15 was 4.7 ± 2.9, FSS 32.9 ± 18.9, PCL‐c 32.6 ± 12.5, SARC‐calf 3.2 ± 4.2. All had mMRC dyspnea classified between 2 and 4. Conclusion: There was a high prevalence of mild cognitive impairment and dementia among patients after three months of discharge, with a predominance of mild frailty due to CFS and the presence of fatigue. It is noteworthy that a quarter of the sample reported low quality of life. [ABSTRACT FROM AUTHOR]

Background: Studies on brain networks indicate that the functional integration between brain networks decreases progressively with Alzheimer's disease (AD). The intermittent Theta Burst Stimulation (ITBS) has been shown to modulate the connectivity of DMN administered to parietal (PPC) and dorsolateral prefrontal (DLPFC) cortex. Method: We selected 9 patients with AD, and a randomized double‐blind clinical trial was performed comparing the active iTBS (n=5) with sham group (n=4)of older adults with mild to moderate AD. Active iTBS condition were submitted to 21 iTBS sessions on the right and left DLPFC and the right and left PPC. All participants were assessed at baseline, week 3,week 6, 3 and 6 months. Executive functions were assessed by validated and standardized tests for this population. Behavioral symptoms were evaluated by Neuropsychiatric Inventory (NPI). The changes in performance between assessments were compared using the reliable change index (RCI). Result: On phonemic verbal fluency two participants from intervention group show decline of this ability. One of them in the 3rd week (RCI = ‐2.16) and in the 6th week (RCI = ‐3.24). And another only in the 6th week (RCI = ‐3.24). After this period, the performance was similar to that of the baseline for both. Despite this, there were three patients who showed change in phonemic verbal fluency in the third week. One participant from sham group also showed improvement in the sixth week (RCI = 2.16). Regarding working memory, a sham participant showed decline in this ability after the sixth week assessment (RCI = ‐7.38) and this performance remained below that presented in the baseline until the sixth month. And another from intervention group showed improvement in the third week (RCI = 2.46), but from the sixth week on, the performance returned to the same level as the baseline. Conclusion: The improvement and impairment of cognitive variables in comparison to baseline was associated with temporal proximity of neurostimulation procedures for both groups. It is still necessary to expand the sample size to clarify which factors impact on this outcomes. [ABSTRACT FROM AUTHOR]

Background: Comparison between functionality and cognition in elderly patients with Alzheimer’s dementia (AD) and without cognitive impairment with positive and negative Aβ‐42 and p‐Tau biomarkers evaluated using the Luminex technique. Method: Patients with Alzheimer’s dementia and normal cognition (control) were recruited. They were divided in two groups according to their clinical diagnosis: AD group (n=30) and control group (CTRL) (n=10). The AD group was then divided in patients with positive (n=21) and negative (n=9) Aβ‐42 and p‐Tau biomarkers. The participants were submitted to sociodemographic. The general cognition was evaluated through the following instruments: the Mini‐Mental State Examination (MMSE), semantic verbal fluency (SVF), animal fluency, short term memory, and recognition of CERAD battery, and functionality was evaluated by the Pfeffer scale. Samples from the cerebrospinal fluid (CSF) of patients were collected, processed, and stored at ‐80°C until use. The Luminex technique was then used for the Aβ‐42, t‐Tau, p‐Tau, t‐Tau/Aβ‐42 ratio, and p‐Tau/Aβ‐42 ratio biomarker analysis. Obtained data was processed and analyzed through the software SPSS 22.0. Result: Comparison between control patients and patients with AD, as defined by clinical diagnosis, did not show significant differences regarding to Aβ‐42 expression in CSF (U=91,000; p=0,067), (AD=1119,0360, SD=708,98952 vs CTRL=775,2623 SD=341,67835). However, there was a significant difference between groups concerning t‐Tau protein, (U=198,500; p=0,028), p‐Tau (U=250,00, p=0,001) and p‐Tau/Aβ‐42 ratio (U=238,00; p=0,005). In terms of cognitive variables, all showed significant differences between groups: MMSE (U=46,500, p=0,001), SVF (U=39,000; p<0,001), short term memory (U=27,000, p<0,001), recognition (U=72,500,p=0,014), as well as functionality (U=258,500, p<0,001). There was no difference regarding the age (U= 201,500; p=0,109) and formal education (U=201,500, p=0,109). As for the AD groups with positive and negative biomarkers, there was no significant difference in cognitive variables, age, formal education, and functionality. Conclusion: AD group with negative biomarkers non differ in terms of cognition. Comparing the control and AD groups, there were differences in functionality, cognition, and biomarkers. However, comparing AD groups in terms of biomarkers, there was no difference in functionality performance, short‐term memory, fluency and general cognition. Therefore, the biomarkers do not indicate significant cognitive differences in the group of patients with dementia. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the association between polymorphisms (SNP) in the tryptophan hydroxylase-2 (TPH2) gene and late-onset depression (LOD) in the Brazilian population. Methods: We genotyped 8 tag SNPs in the TPH2 gene in 84 outpatients with LOD and 79 individuals belonging to the comparison group to investigate an association between the TPH2 gene and LOD. Results: Our findings suggested an association between tag SNP rs4565946 heterozygous C/T (p = 0.034; χ² = 6.7; df = 2) and decreased risk of LOD. The tag SNP rs 11179000 ancestral homozygous A/A (p = 0.025; χ² = 7.3; df = 2) and increase risk of LOD and allelic association of ancestral allele A and increase risk of LOD was demonstrated (p = 0.005; χ² = 7.8; df = 1). Conclusion: We found the statistically significant association between two tag SNPs and LOD. Our results support the hypothesis that the TPH2 gene is associated with LOD. [ABSTRACT FROM AUTHOR]