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Publications (639)
Background: Dementia, marked by cognitive decline, is a global health challenge. Alzheimer's disease (AD), the leading type, accounts for ~70% of cases. Electroencephalography (EEG) measures show promise in identifying AD risk, but obtaining large samples for reliable comparisons is challenging. Objective: This study integrates signal processing, h...
Introduction: Deficits in executive function and processing speed have traditionally been viewed as the chief cognitive manifestation of vascular contributions to cognitive impairment and dementia. This case study describes the longitudinal progression of cognitive symptoms in a 42-year-old Colombian woman with cerebral autosomal dominant arteriopa...
Background:
Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch varia...
Antecedentes y objetivos: menos del 1% de los casos de enfermedad de Alzheimer (EA) son causados por mutacio-nes autosómicas dominantes E280A presenilina 1 (PSEN1) o presenilina 2 (PSEN2), que se relacionan con un inicio tem-prano y acelerada progresión de los síntomas clínicos. Poco se conoce de la relación entre el estado nutricional y los marca-...
INTRODUCTION
Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains.
METHODS
Using an α‐synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27)...
A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch (APOE3Ch) displayed extreme resistance to Alzheimer’s disease (AD) cognitive decline and tauopathy, despite having a high amyloid burden. To further investigate the differences in biological processes attributed to APOE3Ch, we generated induced pluripotent stem (iPS) cell...
INTRODUCTION
Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost‐effective technique for studying dementia globally, but lacks mechanistic models and produces non‐replicable res...
INTRODUCTION
Rate of cognitive decline (RCD) in Alzheimer's disease (AD) determines the degree of impairment for patients and of burden for caretakers. We studied the association of RCD with genetic variants in AD.
METHODS
RCD was evaluated in 62 familial AD (FAD) and 53 sporadic AD (SAD) cases, and analyzed by whole‐exome sequencing for associati...
Objectives:Since its first implementation in 1998, significant evidence has been presented of the positive impact of the TimeSlips creative expression method for people with dementia in long-term care (LTC) settings. Our research with people with dementia in Colombia extends this evidence in important new directions: it is the longest TimeSlips stu...
Contextual memory, the ability to remember spatial or temporal features related to an event, is affected in Alzheimer’s disease (AD). There is a shortfall of tests that measure contextual memory. To evaluate visuospatial contextual memory, we developed a computerized cognitive test, the MAPP Room Memory Test, which requires participants to identify...
Aging diminishes social cognition, and changes in this capacity can indicate brain diseases. However, the relative contribution of age, diagnosis and brain reserve to social cognition, especially among older adults and in global settings, remains unclear when considering other factors. Here, using a computational approach, we combined predictors of...
Background
Multicentric initiatives to study brain cognition in the elderly offers us a unique collection of brain imaging data accompanied by detailed neuroclinical and neuropsychological evaluations. U.S. POINTER and LatAm‐FINGERS, part of the World Wide FINGERS, are both large‐scale investigations of lifestyle interventions and its impact on cog...
Background
Previous work showed that females at risk for autosomal dominant Alzheimer’s disease (AD) due to a single mutation (E280A) in the Presenilin‐1 gene (PSEN1) may have greater cognitive resilience to AD‐pathology and neurodegeneration than males. However, more research is needed to clarify the effect of sex on AD risk and progression. We in...
Background
A number of extended families in Colombia with early‐onset ADAD have a PSEN1 mutation at codon 280 (E280A), comprise the largest ADAD kindred in the world. Trial participants have been treated with crenezumab (an experimental anti‐amyloid monoclonal antibody) or placebo. Topline results were presented in August, 2022 at AAIC. Although th...
Background
Vascular pathology is a main contributor to Alzheimer’s disease (AD) progression and severity. We have previously characterized vascular pathology in the PSEN1E280A Colombian kindred. In postmortem analyses we identified that the occipital cortex (OC) is the most affected region by small vessel disease (SVD), including other cortical are...
Background
We previously examined the impact of using a cerebellar, pons, or cerebral white matter (WM) reference region (RR) on the ability of each to distinguish cortical measures of fibrillar amyloid‐(Aβ) deposition with baseline data in unimpaired presenilin (PSEN1) E280A mutation carriers and non‐carriers (NC) from the Alzheimer’s Prevention I...
Background
Multidomain lifestyle interventions hold great promise world‐wide as interventions to slow cognitive aging, and delay and prevent Alzheimer’s Disease and Related Disorders (ADRD). To have the greatest reach, they must be tailored for and assessed within local cultures in clinical trials. For trials to have the greatest impact, it’s impor...
Background
Autosomal Dominant Alzheimer’s disease (ADAD) is a subtype of AD in which the symptoms begin before age 65. ADAD is an important subtype of AD as it affects people at productive and reproductive age, has a genetic origin in most of the cases and is one of the 10 causes of years lost to disability (YDLs) (1). Colombia has the largest kind...
Background
Recruiting cognitively‐unimpaired volunteers at high genetic risk of developing dementia into the Alzheimer’s Prevention Initiative (API) Colombia trial, and maintaining study adherence for at least 5 years has been a monumental challenge. Major barriers included inclusion criteria, protocol visit schedule, long informed consent form (IC...
Background
We previously reported a case of a homozygous woman with the APOE3 Christchurch (R136S, APOE3Ch) variant who demonstrated extreme resistance to autosomal dominant Alzheimer’s disease (ADAD) caused by the PSEN1 E280A variant. In this study, we examined the potential protective effects of APOE3Ch against ADAD by characterizing the clinical...
Background
the study of the medium and long‐term consequences of coronavirus infection (SARS‐CoV‐2) is of great relevance from the clinical and public health perspective. Recent evidence has shown that patients may present cognitive complaints after overcoming the acute stage of infection, particularly memory disturbances. Although significant prog...
Background
In most prevention clinical trials contraceptive use is required. The API ADAD Colombia Trial was a phase II, double‐blind, placebo‐controlled clinical trial to evaluate the safety and efficacy of the investigational product crenezumab. Trial period A was carried out from 2013 to 2021, during which 252 cognitively unimpaired PSEN1 E280A...
Background
Alzheimer’s disease (AD) is the leading cause of dementia in the world. Synaptic dysfunction is a pathophysiological event that alters neuronal connections at multiple scales: molecular, cellular, brain networks, cerebral cortex, among others. There are different mechanisms that interact to trigger alterations in the homeostasis of synap...
Background
Greater aerobic fitness, objectively measured by VO2‐max, is considered a critical component of overall health and a strong predictor of cognitive functioning. It has been associated with less neurodegeneration in Alzheimer’s disease (AD) and greater functional brain connectivity and plasticity in healthy older adults. Yet, less is known...
Background
LatAm‐FINGERS is the first non‐pharmacological multicenter randomized clinical trial to prevent cognitive impairment in Latin America (LA). The trial congregates the effort of 12 Countries, including Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Peru, Puerto Rico, and Uruguay. The main aim...
Background
We have described two cases with ∼ 30 years of delayed disease onset among carriers of PSEN1 mutation E280A, suffering from familial Alzheimer’s disease (FAD). One case was homozygous for the ApoE Christchurch (hApoEch) mutation. This case showed sparse hyperphosphorylated tau (pTau) pathology in several cortical areas. The second case w...
Background
The cognitive reserve (CR) has been associated with the extension/compensation of the mental functioning of individuals affected by a neurodegenerative disease in the early stages of the disease. Most of the analyses evaluating CR are in high‐income countries, while there is a lack of capturing the variability related to low‐middle‐incom...
Background
Hypometabolism is observed in early Alzheimer’s disease (AD), though its relation to underlying pathology remains uncertain. We first examined the relationships between glucose metabolism, β‐amyloid (Aβ), and tau in Presenilin‐1 ( PSEN1 ) E280A mutation carriers and non‐carriers from the Massachusetts General Hospital Colombia‐Boston (CO...
Objective
Contextual memory, which refers to the ability to remember spatial or temporal circumstances related to an event, is affected early in Alzheimer’s Disease (AD). Computerized cognitive tasks have been suggested to be an ecological way to assess memory, but there are few studies that utilize these tools. Studying contextual memory via a com...
Objective
High levels of stress may increase risk for Alzheimer’s disease (AD) dementia. Religious coping practices to deal with stress (i.e., prayer, having faith, attending religious services) may reduce risk of dementia. Studying religious stress coping in cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dem...
Objective
Neurofilament light chain (NfL), a plasma-based biomarker for neurodegeneration, is a promising marker for early Alzheimer disease (AD) detection in individuals at increased risk. We previously reported that Presenilin1 (PSEN1) E280A carriers have increased levels of plasma NfL relative to non-carrier family members twenty years before th...
Objective
Semantic processing dysfunction has been shown to be an early indicator of cognitive decline in Alzheimer's disease (AD) and has been linked to early accumulation of AD-pathology. We examined semantic processing and its relation to AD pathology in non-demented individuals from a Colombian kindred with autosomal dominant AD due to the Pres...
Objective
Associative memory is impacted early in Alzheimer’s disease (AD). Poorer performance on associative memory tests has been related to greater amyloid and regional tau burden in preclinical AD. Our group previously examined the association of brain pathology and performance on the Free and Cued Selective Reminding Test (FCSRT) in Autosomal...
Objective
Sleep contributes to memory retention and recall. Alzheimer’s disease (AD) patients experience decreased slow wave activity (SWA) during sleep. This decrease in SWA is associated with impaired memory consolidation (Lee et al., 2020). Long-term forgetting (LTF) over days or weeks has been linked to memory consolidation deficits and has bee...
Background
“Brain-predicted age” estimates biological age from complex, nonlinear features in neuroimaging scans. The brain age gap (BAG) between predicted and chronological age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD), in which AD progression is highly predictable with minimal confounding...
The Latin American Brain Health Institute (BrainLat) has released a unique multimodal neuroimaging dataset of 780 participants from Latin American. The dataset includes 530 patients with neurodegenerative diseases such as Alzheimer’s disease (AD), behavioral variant frontotemporal dementia (bvFTD), multiple sclerosis (MS), Parkinson’s disease (PD),...
Objective: Evaluate the reliability of neural components obtained from the application of the group ICA (gICA) methodology to resting-state EEG datasets acquired from multiple sites.
Methods: Five databases from three sites, covering a total of 292 healthy subjects, were analyzed. Each dataset was segmented into groups of 15 subjects, for a total...
The Electroencephalogram (EEG) provides a very high temporal resolution of brain
activity. This allows for directly recording the electromagnetic activity of the brain during cognitive tasks. In theory, the EEG contains important discriminative information
relating to sequential processes of the brain’s response to different tasks. Using measures o...
Objective: Evaluate the reliability of neural components obtained from the group ICA (gICA) methodology applied to resting-state EEG datasets acquired from multiple sites.
Methods: Five databases from 3 sites, covering a total of 292 healthy subjects, were analyzed. Each dataset was segmented into groups of 15 subjects, for a total of 19 groups. Da...
Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD), leading to earlier age of clinical onset and exacerbating pathologies. There is a critical need to identify protective targets. Recently, a rare APOE variant, APOE3-R136S (Christchurch), was found to protect against early-onset AD in a PSEN1-E2...
Importance
Increased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic...
INTRODUCTION
Depressive symptoms are among early behavioral changes in Alzheimer's disease (AD); however, the relationship between neurodegeneration and depressive symptoms remains inconclusive. To better understand this relationship in preclinical AD, we examined hippocampal volume and depressive symptoms in cognitively unimpaired carriers of the...
Objective
Declines in non-verbal reasoning abilities have been linked to Alzheimer’s disease (ad) progression. Individuals with autosomal dominant ad (ADAD) are genetically determined to develop early-onset dementia. We examined the relation between non-verbal reasoning abilities and brain pathology in a Colombian cohort with ADAD due to the Presen...
INTRODUCTION
We discovered that the APOE3 Christchurch (APOE3Ch) variant may provide resistance to Alzheimer's disease (AD). This resistance may be due to reduced pathological interactions between ApoE3Ch and heparan sulfate proteoglycans (HSPGs).
METHODS
We developed and characterized the binding, structure, and preclinical efficacy of novel anti...
INTRODUCTION
Studies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD).
METHODS
Three hundred twenty‐five mutation carriers (55...
Background:
The SARS-CoV2 global pandemic impacted participants in the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) clinical trial, who faced three stressors: 1) fear of developing dementia; 2) concerns about missing treatment; and 3) the possibility of becoming infected with SARS-CoV2.
Objective:
To desc...
Autosomal dominant Alzheimer’s disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E ( APOE ) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To inve...
Familial Alzheimer’s disease (FAD) is a complex neurodegenerative disorder for which there are no therapeutics to date. Several mutations in presenilin 1 (PSEN 1), which is the catalytic component of γ-secretase complex, are causal of FAD. Recently, the p.Ile416Thr (I416T) PSEN 1 mutation has been reported in large kindred in Colombia. However, cel...
Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease m...
Background:
Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear.
Objective:
The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort.
Methods:
We used data from three...
Alzheimer’s disease (AD) represents a substantial burden to patients, their caregivers, health systems, and society in Latin America and the Caribbean (LAC). This impact is exacerbated by limited access to diagnosis, specialized care, and therapies for AD within and among nations. The region has varied geographic, ethnic, cultural, and economic con...
Background
Awareness of memory was previously found to be reduced in the pre‐dementia stages, reaching unawareness/anosognosia 6‐years before dementia onset in individuals who carry the PSEN1 E280A mutation for autosomal dominant Alzheimer’s disease (Vannini et al.,2021). Whether there are potential differences in awareness for specific types of si...
Background
Long‐term forgetting (LTF) over days or weeks may be a sensitive early marker of Alzheimer’s disease (AD), useful for preclinical AD trials. We examined associations between LTF and markers of brain pathology in individuals from the world’s largest kindred with autosomal dominant AD due to the Presenilin‐1 (PSEN1) E280A mutation.
Method...
Background
Cerebrospinal fluid (CSF) biomarkers have potentially important roles in Alzheimer’s disease (AD) treatment and prevention trials. The Alzheimer’s Prevention Initiative Autosomal‐Dominant AD (API ADAD) trial protocol (NCT01998841) includes optional CSF biomarker measurements at baseline, 24 months, and 60 months. We determined the adhere...
Background
Some but not all studies have found compromised myocardial function and amyloid deposition, related or unrelated to amyloid‐β pathology itself, in persons with late‐onset Alzheimer’s Disease (AD). Other changes in QT interval, heart rate variability, and QRS voltages have been described in the electrocardiogram (ECG), but those are not c...
Background
The disruption of brain functional connections has been linked to cognitive impairment in Alzheimer’s disease. The functional architecture of the brain can be modeled using graph theory, which provides metrics to describe both local and global network properties. Autosomal dominant Alzheimer’s disease (ADAD) provides a unique opportunity...
Introduction:
Plasma tau phosphorylated at threonine 217 (P-tau217) and neurofilament light (NfL) have emerged as markers of Alzheimer's disease (AD) pathology. Few studies have examined the role of sex in plasma biomarkers in sporadic AD, yielding mixed findings, and none in autosomal dominant AD.
Methods:
We examined the effects of sex and age...
Aging may diminish social cognition, which is crucial for interaction with others, and significant changes in this capacity can indicate pathological processes like dementia. However, the extent to which non-specific factors explain variability in social cognition performance, especially among older adults and in global settings, remains unknown. A...
Introduction:
Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization....
Alzheimer’s disease (AD) is a chronic neurological condition characterized by the severe loss of cholinergic neurons. Currently, the incomplete understanding of the loss of neurons has prevented curative treatments for familial AD (FAD). Therefore, modeling FAD in vitro is essential for studying cholinergic vulnerability. Moreover, to expedite the...
We characterized the world’s second case with ascertained extreme resilience to autosomal dominant Alzheimer’s disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact...
Objectives
Alzheimer’s disease (AD) is known to impact semantic access, which is frequently evaluated using the Category Fluency (Animals) test. Recent studies have suggested that in addition to overall category fluency scores (total number of words produced over time), poor clustering could signal AD-related cognitive difficulties. In this study,...
Objective:
This study aims 1) To analyse differences in resting-state electroencephalogram (rs-EEG) spectral features of Parkinson's Disease (PD) and healthy subjects (non-PD) using Functional Data Analysis (FDA) and 2) To explore, in four independent cohorts, the external validity and reproducibility of the findings using both epoch-to-epoch FDA...
Introduction:
Genetic associations with Alzheimer's disease (AD) age at onset (AAO) could reveal genetic variants with therapeutic applications. We present a large Colombian kindred with autosomal dominant AD (ADAD) as a unique opportunity to discover AAO genetic associations.
Methods:
A genetic association study was conducted to examine ADAD AA...
Background:
Depression is associated with Alzheimer's disease (AD).
Objective:
To evaluate the association between depressive symptoms and age of onset of cognitive decline in autosomal dominant AD, and to determine possible factors associated to early depressive symptoms in this population.
Methods:
We conducted a retrospective study to ident...
Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium...
Early cognitive changes due to Alzheimer’s disease (AD) include difficulties in semantic access and working memory. Using a computerized cognitive test developed by our group, called the Memory for Semantically Related Objects test (MESERO), we evaluated if cognitively unimpaired carriers of an autosomal dominant AD (ADAD) mutation performed worse...