Assessing subjective cognitive decline in older adults attending primary health care centers: what question should be asked?

INTRODUCTION: Subjective Cognitive Decline (SCD) refers to a self-perceived experience of decreased cognitive function without objective signs of cognitive impairment in neuropsychological tests or daily living activities. Despite the abundance of instruments addressing SCD, there is no consensus on the methods to be used. Our study is founded on 11 questions selected due to their recurrence in most instruments. The objective was to determine which one of these questions could be used as a simple screening tool. METHODS: 189 participants aged 65 and over selected from Primary Care centers in Santiago de Chile responded to these 11 questions and were evaluated with the MiniMental State Examination (MMSE), the Free and Cued Selective Reminding Test (FCSRT), the Pfeffer functional scale, and the Geriatric Depression Scale (GDS). An Item ResponseTheory (IRT) method was performed to assess the contribution of each of the 11 questions to the SCD latent trait and its discrimination ability. RESULTS: Based on the results of the exploratory factor analysis showing very high/low saturation of several questions on the factors, and the high residual correlation between some questions, the IRT methods led to select one question ("Do you feel like your memory has become worse?") which revealed to be the most contributive and discriminant. Participants who answered yes had a higher GDS score. There was no association with MMSE, FCSRT, and Pfeffer scores. CONCLUSION: The question "Do you feel like your memory has become worse?" may be a good proxy of SCD and could be included in routine medical checkups.

The "when" matters: Evidence from memory markers in the clinical continuum of Alzheimer's disease.

OBJECTIVE: Cognitive assessment able to detect impairments in the early neuropathological stages of Alzheimer's disease (AD) is urgently needed. The visual short-term memory binding task (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT) have been recommended by the neurodegenerative disease working group as promising tests to aid in the early detection of AD. In this study, we investigated their complementary value across the clinical stages of the AD continuum. METHOD: One hundred and seventeen older adults with subjective cognitive complaint (SCC), 79 with mild cognitive impairment (MCI), 31 patients with AD dementia (ADD), and 37 cognitively unimpaired (CU) subjects, underwent assessment with the VSTMBT and the picture version of the Spanish FCSRT. RESULTS: After controlling for multiple comparisons, significant differences were found across groups. The VSTMBT was the only test that "marginally" differentiated between CU and SCC (d = 0.47, p = .052). Moreover, whereas the FCSRT showed a gradient (CU = SCC) > MCI > ADD, the VSTMBT gradient was CU > SCC > (MCI = ADD) suggesting that conjunctive binding deficits assessed by the latter may be sensitive to the very early stages of the disease. CONCLUSIONS: Our results suggest that the VSTMBT and the FCSRT are sensitive to the clinical continuum of AD. Whereas the former detects changes in the early prodromal stages, the latter is more sensitive to the advanced prodromal stages of AD. These novel tests can aid in the early detection, monitor disease progression and response to treatment, and thus support drug development programs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Insulin-like growth factor 2 and autophagy gene expression alteration arise as potential biomarkers in Parkinson's disease.

Insulin-like growth factor 2 (IGF2) and autophagy-related genes have been proposed as biomolecules of interest related to idiopathic Parkinson's disease (PD). The objective of this study was to determine the IGF2 and IGF1 levels in plasma and peripheral blood mononuclear cells (PBMCs) from patients with moderately advanced PD and explore the potential correlation with autophagy-related genes in the same blood samples. IGF1 and IGF2 levels in patients' plasma were measured by ELISA, and the IGF2 expression levels were determined by real-time PCR and Western blot in PBMCs. The expression of autophagy-related genes was evaluated by real-time PCR. The results show a significant decrease in IGF2 plasma levels in PD patients compared with a healthy control group. We also report a dramatic decrease in IGF2 mRNA and protein levels in PBMCs from PD patients. In addition, we observed a downregulation of key components of the initial stages of the autophagy process. Although IGF2 levels were not directly correlated with disease severity, we found a correlation between its levels and autophagy gene profile expression in a sex-dependent pattern from the same samples. To further explore this correlation, we treated mice macrophages cell culture with α-synuclein and IGF2. While α-synuclein treatment decreased levels Atg5, IGF2 treatment reverted these effects, increasing Atg5 and Beclin1 levels. Our results suggest a relationship between IGF2 levels and the autophagy process in PD and their potential application as multi-biomarkers to determine PD patients' stages of the disease.

Automated text-level semantic markers of Alzheimer's disease.

INTRODUCTION: Automated speech analysis has emerged as a scalable, cost-effective tool to identify persons with Alzheimer's disease dementia (ADD). Yet, most research is undermined by low interpretability and specificity. METHODS: Combining statistical and machine learning analyses of natural speech data, we aimed to discriminate ADD patients from healthy controls (HCs) based on automated measures of domains typically affected in ADD: semantic granularity (coarseness of concepts) and ongoing semantic variability (conceptual closeness of successive words). To test for specificity, we replicated the analyses on Parkinson's disease (PD) patients. RESULTS: Relative to controls, ADD (but not PD) patients exhibited significant differences in both measures. Also, these features robustly discriminated between ADD patients and HC, while yielding near-chance classification between PD patients and HCs. DISCUSSION: Automated discourse-level semantic analyses can reveal objective, interpretable, and specific markers of ADD, bridging well-established neuropsychological targets with digital assessment tools.

Caracterización clínica e imagenológica de una serie de pacientes con disección de arterias cervicales e intracraneales / Cervicocranial arterial dissection: experience in 57 patients

Background: Cervicocranial arterial dissection (CIAD) is an important cause of stroke. Aim: To describe the clinical and imaging characteristics of patients with CIAD. Material and Methods: An anonymous registry was made including all patients admitted to a private hospital with a diagnosis of CIAD. Patients were subdivided as having an anterior or posterior circulation dissection (ACD or PCD, respectively). Results: Fifty-seven patients aged 40 ± 8 years (60% women) were included in the study, 39 with PCD and 18 with ACD. Cervical pain was the most common symptom. CIAD was diagnosed with no clinical or imaging signs of stroke in 49% of patients. Fifty one percent of patients had focal neurological deficits and 72% had a NIH stroke score below five. No significant differences between patients with ACD or PCD were found. Fifty patients received antiplatelet therapy (simple or dual), seven patients were anticoagulated and 13 were subjected to stenting due to progression of stenosis with hemodynamic involvement or bilateral dissection with scarce collaterals. The lesion was located in V3 segment in 27 patients and cervical segment of the internal carotid in 16 cases. A favorable Modified Rankin Scale (0-2) was achieved in 85.9%, with a trend towards achieving better functional prognosis in PCD. Conclusions: Due to the greater availability of non-invasive imaging methods, 50% of these patients with CIAD did not have a stroke. Thus, an earlier and more timely management is feasible.

Interoception Primes Emotional Processing: Multimodal Evidence from Neurodegeneration.

Recent frameworks in cognitive neuroscience and behavioral neurology underscore interoceptive priors as core modulators of negative emotions. However, the field lacks experimental designs manipulating the priming of emotions via interoception and exploring their multimodal signatures in neurodegenerative models. Here, we designed a novel task that involves interoceptive and control-exteroceptive priming conditions followed by post-interoception and post-exteroception facial emotion recognition (FER). We recruited 114 participants, including healthy controls (HCs) as well as patients with behavioral variant frontotemporal dementia (bvFTD), Parkinson's disease (PD), and Alzheimer's disease (AD). We measured online EEG modulations of the heart-evoked potential (HEP), and associations with both brain structural and resting-state functional connectivity patterns. Behaviorally, post-interoception negative FER was enhanced in HCs but selectively disrupted in bvFTD and PD, with AD presenting generalized disruptions across emotion types. Only bvFTD presented impaired interoceptive accuracy. Increased HEP modulations during post-interoception negative FER was observed in HCs and AD, but not in bvFTD or PD patients. Across all groups, post-interoception negative FER correlated with the volume of the insula and the ACC. Also, negative FER was associated with functional connectivity along the (a) salience network in the post-interoception condition, and along the (b) executive network in the post-exteroception condition. These patterns were selectively disrupted in bvFTD (a) and PD (b), respectively. Our approach underscores the multidimensional impact of interoception on emotion, while revealing a specific pathophysiological marker of bvFTD. These findings inform a promising theoretical and clinical agenda in the fields of nteroception, emotion, allostasis, and neurodegeneration.SIGNIFICANCE STATEMENT We examined whether and how emotions are primed by interoceptive states combining multimodal measures in healthy controls and neurodegenerative models. In controls, negative emotion recognition and ongoing HEP modulations were increased after interoception. These patterns were selectively disrupted in patients with atrophy across key interoceptive-emotional regions (e.g., the insula and the cingulate in frontotemporal dementia, frontostriatal networks in Parkinson's disease), whereas persons with Alzheimer's disease presented generalized emotional processing abnormalities with preserved interoceptive mechanisms. The integration of both domains was associated with the volume and connectivity (salience network) of canonical interoceptive-emotional hubs, critically involving the insula and the anterior cingulate. Our study reveals multimodal markers of interoceptive-emotional priming, laying the groundwork for new agendas in cognitive neuroscience and behavioral neurology.

[Cervicocranial arterial dissection. Experience in 57 patients]. / Caracterización clínica e imagenológica de una serie de pacientes con disección de arterias cervicales e intracraneales.

BACKGROUND: Cervicocranial arterial dissection (CIAD) is an important cause of stroke. AIM: To describe the clinical and imaging characteristics of patients with CIAD. MATERIAL AND METHODS: An anonymous registry was made including all patients admitted to a private hospital with a diagnosis of CIAD. Patients were subdivided as having an anterior or posterior circulation dissection (ACD or PCD, respectively). RESULTS: Fifty-seven patients aged 40 ± 8 years (60% women) were included in the study, 39 with PCD and 18 with ACD. Cervical pain was the most common symptom. CIAD was diagnosed with no clinical or imaging signs of stroke in 49% of patients. Fifty one percent of patients had focal neurological deficits and 72% had a NIH stroke score below five. No significant differences between patients with ACD or PCD were found. Fifty patients received antiplatelet therapy (simple or dual), seven patients were anticoagulated and 13 were subjected to stenting due to progression of stenosis with hemodynamic involvement or bilateral dissection with scarce collaterals. The lesion was located in V3 segment in 27 patients and cervical segment of the internal carotid in 16 cases. A favorable Modified Rankin Scale (0-2) was achieved in 85.9%, with a trend towards achieving better functional prognosis in PCD. CONCLUSIONS: Due to the greater availability of non-invasive imaging methods, 50% of these patients with CIAD did not have a stroke. Thus, an earlier and more timely management is feasible.

GERO Cohort Protocol, Chile, 2017-2022: Community-based Cohort of Functional Decline in Subjective Cognitive Complaint elderly.

BACKGROUND: With the global population aging and life expectancy increasing, dementia has turned a priority in the health care system. In Chile, dementia is one of the most important causes of disability in the elderly and the most rapidly growing cause of death in the last 20 years. Cognitive complaint is considered a predictor for cognitive and functional decline, incident mild cognitive impairment, and incident dementia. The GERO cohort is the Chilean core clinical project of the Geroscience Center for Brain Health and Metabolism (GERO). The objective of the GERO cohort is to analyze the rate of functional decline and progression to clinical dementia and their associated risk factors in a community-dwelling elderly with subjective cognitive complaint, through a population-based study. We also aim to undertake clinical research on brain ageing and dementia disorders, to create data and biobanks with the appropriate infrastructure to conduct other studies and facilitate to the national and international scientific community access to the data and samples for research. METHODS: The GERO cohort aims the recruitment of 300 elderly subjects (> 70 years) from Santiago (Chile), following them up for at least 3 years. Eligible people are adults not diagnosed with dementia with subjective cognitive complaint, which are reported either by the participant, a proxy or both. Participants are identified through a household census. The protocol for evaluation is based on a multidimensional approach including socio-demographic, biomedical, psychosocial, neuropsychological, neuropsychiatric and motor assessments. Neuroimaging, blood and stool samples are also obtained. This multidimensional evaluation is carried out in a baseline and 2 follow-ups assessments, at 18 and 36 months. In addition, in months 6, 12, 24, and 30, a telephone interview is performed in order to keep contact with the participants and to assess general well-being. DISCUSSION: Our work will allow us to determine multidimensional risks factors associated with functional decline and conversion to dementia in elderly with subjective cognitive complain. The aim of our GERO group is to establish the capacity to foster cutting edge and multidisciplinary research on aging in Chile including basic and clinical research. TRIAL REGISTRATION: NCT04265482 in ClinicalTrials.gov. Registration Date: February 11, 2020. Retrospectively Registered.

Epidemiology of chronic inflammatory demyelinating polyneuropathy in the South-Eastern area of Santiago, Chile.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated polyneuropathy. It usually has an insidious onset, progressive course and heterogeneous clinical features. As far as we know, there is no epidemiological information on CIDP in South America and the Caribbean. Our aim was to estimate the frequency of CIDP in the South-Eastern region of Santiago, where our hospital is based and the population number assigned is officially reported every year by the health authorities. Records of 581 patients registered with the diagnosis of neuropathy were found and all patients meeting the diagnostic criteria of the EFNS/PNS for definitive and possible CIDP were included. Data were collected using a data extraction protocol designed by the authors and which included demographic, clinical, laboratory and electrophysiological information. The estimated prevalence and incidence of CIDP were 2.95/100,000 and 0.46/100,000 respectively. Fifteen patients (8 men, 7 women) were classified as definitive or possible CIDP. Nine patients had typical CIDP and three also had diabetes mellitus. The prevalence and incidence rates were similar to those reported in other regions of the world.

Alzheimer's Disease or Behavioral Variant Frontotemporal Dementia? Review of Key Points Toward an Accurate Clinical and Neuropsychological Diagnosis.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common neurodegenerative early-onset dementias. Despite the fact that both conditions have a very distinctive clinical pattern, they present with an overlap in their cognitive and behavioral features that may lead to misdiagnosis or delay in diagnosis. The current review intends to summarize briefly the main differences at the clinical, neuropsychological, and behavioral levels, in an attempt to suggest which aspects would facilitate an adequate diagnosis in a clinical setting, especially in Latin American and low- and middle-income countries, where the resources needed for a differential diagnosis (such as MRI or biomarkers) are not always available. A timely diagnosis of AD and FTD have significant implications for the medical management and quality of life of patients and careers.

Dopamine Receptor D3 Expression Is Altered in CD4+ T-Cells From Parkinson's Disease Patients and Its Pharmacologic Inhibition Attenuates the Motor Impairment in a Mouse Model.

Neuroinflammation constitutes a fundamental process involved in Parkinson's disease (PD). Microglial cells play a central role in the outcome of neuroinflammation and consequent neurodegeneration of dopaminergic neurons in the substantia nigra. Current evidence indicates that CD4+ T-cells infiltrate the brain in PD, where they play a critical role determining the functional phenotype of microglia, thus regulating the progression of the disease. We previously demonstrated that mice bearing dopamine receptor D3 (DRD3)-deficient CD4+ T-cells are completely refractory to neuroinflammation and consequent neurodegeneration induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study we aimed to determine whether DRD3-signalling is altered in peripheral blood CD4+ T-cells obtained from PD patients in comparison to healthy controls (HC). Furthermore, we evaluated the therapeutic potential of targeting DRD3 confined to CD4+ T-cells by inducing the pharmacologic antagonism or the transcriptional inhibition of DRD3-signalling in a mouse model of PD induced by the chronic administration of MPTP and probenecid (MPTPp). In vitro analyses performed in human cells showed that the frequency of peripheral blood Th1 and Th17 cells, two phenotypes favoured by DRD3-signalling, were significantly increased in PD patients. Moreover, naïve CD4+ T-cells obtained from PD patients displayed a significant higher Th1-biased differentiation in comparison with those naïve CD4+ T-cells obtained from HC. Nevertheless, DRD3 expression was selectively reduced in CD4+ T-cells obtained from PD patients. The results obtained from in vivo experiments performed in mice show that the transference of CD4+ T-cells treated ex vivo with the DRD3-selective antagonist PG01037 into MPTPp-mice resulted in a significant reduction of motor impairment, although without significant effect in neurodegeneration. Conversely, the transference of CD4+ T-cells transduced ex vivo with retroviral particles codifying for an shRNA for DRD3 into MPTPp-mice had no effects neither in motor impairment nor in neurodegeneration. Notably, the systemic antagonism of DRD3 significantly reduced both motor impairment and neurodegeneration in MPTPp mice. Our findings show a selective alteration of DRD3-signalling in CD4+ T-cells from PD patients and indicate that the selective DRD3-antagonism in this subset of lymphocytes exerts a therapeutic effect in parkinsonian animals dampening motor impairment.

Aging and Health Policies in Chile: New Agendas for Research.

Abstract-Population aging is among the most important global transformations. Compared to European and North American countries, Chile is among the countries with the fastest growth of life expectancy at birth during recent decades. The aging of Chile's population is related to the improvement of living conditions, but also entails risks that tend to be associated with a rapid economic growth accompanied by large income inequalities and a chronic deficit of basic social benefits. The rapid demographic transition towards an aged population has unfolded in a context of poor development of public policies to tackle the opportunities and needs associated with an aging society. This article provides a brief overview of current Chilean public policy on aging, with a focus on healthy aging as defined by World Health Organization. The discussion addresses core challenges to successfully achieve healthy aging in Chile.

Investigation of c9orf72 in 4 neurodegenerative disorders.

OBJECTIVE To estimate the allele frequency of C9orf72 (G4C2) repeats in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer disease (AD), and Parkinson disease (PD). DESIGN The number of repeats was estimated by a 2-step genotyping strategy. For expansion carriers, we sequenced the repeat flanking regions and obtained APOE genotypes and MAPT H1/H2 haplotypes. SETTING Hospitals specializing in neurodegenerative disorders. SUBJECTS We analyzed 520 patients with FTLD, 389 patients with ALS, 424 patients with AD, 289 patients with PD, 602 controls, 18 families, and 29 patients with PD with the LRRK2 G2019S mutation. MAIN OUTCOME MEASURE The expansion frequency. RESULTS Based on a prior cutoff (>30 repeats), the expansion was detected in 9.3% of patients with ALS, 5.2% of patients with FTLD, and 0.7% of patients with PD but not in controls or patients with AD. It was significantly associated with family history of ALS or FTLD and age at onset of FTLD. Phenotype variation (ALS vs FTLD) was not associated with MAPT, APOE, or variability in the repeat flanking regions. Two patients with PD were carriers of 39 and 32 repeats with questionable pathological significance, since the 39-repeat allele does not segregate with PD. No expansion or intermediate alleles (20-29 repeats) were found among the G2019S carriers and AD cases with TAR DNA-binding protein 43-positive inclusions. Surprisingly, the frequency of the 10-repeat allele was marginally increased in all 4 neurodegenerative diseases compared with controls, indicating the presence of an unknown risk variation in the C9orf72 locus. CONCLUSIONS The C9orf72 expansion is a common cause of ALS and FTLD, but not of AD or PD. Our study raises concern about a reliable cutoff for the pathological repeat number, which is important in the utility of genetic screening.

Association of GST M1 null polymorphism with Parkinson's disease in a Chilean population with a strong Amerindian genetic component.

We have studied the association of a null mutation of Glutathione Transferase M1 (GST M1*0/0) with Parkinson's disease (MIM 168600) in a Chilean population with a strong Amerindian genetic component. We determined the genotype in 349 patients with idiopathic Parkinson's disease (174 female and 175 male; 66.84+/-10.7 years of age), and compared that to 611 controls (457 female and 254 male; 62+/-13.4 years of age). A significant association of the null mutation in GST M1 with Parkinson's disease was found (p=0.021), and the association was strongest in the earlier age range. An association of GSTM1*0/0 with Parkinson's disease supports the hypothesis that Glutathione Transferase M1 plays a role in protecting astrocytes against toxic dopamine oxidative metabolism, and most likely by preventing toxic one-electron reduction of aminochrome.