Alberto Villarejo-Galende

• MD
• attending neurologist at Hospital 12 de Octubre

Purpose: We aimed to address fears and lived experiences of cognitive decline among adults via whole-person conversations that elicit problems and goals that matter most to patients. Currently, 6.7 million Americans have Alzheimer disease or related dementias, with an additional 28 million people reporting subjective cognitive decline-a possible i...

Alzheimer’s disease (AD), the most common cause of dementia, is a complex and multifactorial condition without cure at present. The latest treatments, based on anti-amyloid monoclonal antibodies, have only a modest effect in reducing the progression of cognitive decline in AD, whereas the possibility of preventing AD has become a crucial area of re...

Objective To estimate the test-retest and inter-rater reliability of the new Spanish abbreviated version of the Luria Neuropsychological Diagnosis (DNA-2) battery for older adults. Method A total of thirty cognitively healthy volunteers were examined in this study. The participants completed a comprehensive standardized assessment, encompassing c...

Background and Objectives Older adults experiencing neurocognitive disease (NCD) contend with complex care often characterized by high emotional strain. Mitigating complex care with decision support tools can clarify options. When used in conjunction with the practice of Shared Decision Making (SDM) these tools can improve satisfaction and confiden...

INTRODUCTION Biomarker‐informed criteria were proposed for the diagnosis of Alzheimer's disease (AD) by the National Institute on Aging and the Alzheimer's Association (NIA‐AA) in 2011; however, the adequacy of this criteria has not been sufficiently evaluated. METHODS ReDeMa ( Red de Demencias de Madrid ) is a regional cohort of patients attendin...

Background Limited information is available on the active process of seeking medical help in patients with Alzheimer’s disease (AD) at early stages. The aim of this study was to assess the phenomenon of medical help-seeking in early AD and to identify associated factors. Methods A multicenter, non-interventional study was conducted including patie...

Introduction. Limbic encephalitis (LE) can have a wide range of etiologies, most frequently infectious (especially viral) or autoimmune. Behçet’s disease (BD) can present with heterogeneous neurological manifestations. However, LE is not considered a typical presentation of neuro-Behçet’s disease (NBD). Case report. A 40-years-old male presented wi...

Introduction: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an entity characterised by an inflammatory response to β-amyloid deposition in the walls of cerebral microvessels. Methods: We conducted a retrospective review of a series of patients with a diagnosis of CAA-ri according to histopathological study findings or clinical-rad...

Objective: To study the correlation between a static PET image of the first-minute-frame (FMF) acquired with 18F-labeled amyloid-binding radiotracers and brain [18F]FDG PET in patients with primary progressive aphasia (PPA). Material and methods: The study cohort includes 17 patients diagnosed with PPA with the following distribution: 9 nonfluen...

Neurodegenerative parkinsonisms affect mainly cognitive and motor functions and are syndromes of overlapping symptoms and clinical manifestations such as tremor, rigidness, and bradykinesia. These include idiopathic Parkinson’s disease (PD) and the atypical parkinsonisms, namely progressive supranuclear palsy (PSP), corticobasal degeneration (CBD),...

Background There is a need to better understand the experience of patients living with Alzheimer's disease (AD) in the early stages. Objective The aim of the study was to evaluate the perception of quality of life in patients with early-stage AD. Methods A multicenter, non-interventional study was conducted including patients of 50–90 years of ag...

Introduction: Limited information is available on people's experiences of living with Alzheimer's disease (AD) at earlier stages. This study assessed awareness of diagnosis among people with early-stage AD and its impact on different person-centered outcome measures. Methods: We conducted an observational, cross-sectional study in 21 memory clin...

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive vascular disorder caused by biallellic variants in HTRA1. Recently, it has been reported that several heterozygous mutations in HTRA1 are responsible for a milder late-onset cerebral small vessel disease (CSVD) with an aut...

In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL...

Background and Objectives To investigate the natural history and outcomes following treatment for spontaneous amyloid-related imaging abnormalities (ARIA)-like in cerebral amyloid angiopathy-related inflammation (CAA-ri). Methods A multicenter, hospital-based, longitudinal, prospective observational study of inpatients meeting CAA-ri diagnostic cr...

The haploinsufficiency of the methyl-binding domain protein 5 (MBD5) gene has been identified as the determinant cause of the neuropsychiatric disorders grouped under the name MBD5-neurodevelopment disorders (MAND). MAND includes patients with intellectual disability, behavioral problems, and seizures with a static clinical course. However, a few r...

Neuroinflammation is a common feature in Alzheimer’s (AD) and Parkinson’s (PD) disease. In the last few decades, a testable hypothesis was proposed that protein-unfolding events might occur due to neuroinflammatory cascades involving alterations in the crosstalk between glial cells and neurons. Here, we tried to clarify the pattern of two of the mo...

Dynamic early-phase PET images acquired with radiotracers binding to fibrillar amyloid-beta (Aβ) have shown to correlate with [¹⁸F]fluorodeoxyglucose (FDG) PET images and provide perfusion-like information. Perfusion information of static PET scans acquired during the first minute after radiotracer injection (FMF, first-minute-frame) is compared to...

To investigate whether physical activity (PA) is a protective factor for the incidence of Parkinsońs disease (PD) and parkinsonism after three years of follow-up. All participants of this study were obtained from the Neurological Disorders in Central Spain (NEDICES), a prospective population-based cohort survey of older subjects (≥ 65 years) that c...

Objective: SQSTM1-variants associated with frontotemporal lobar degeneration have been described recently. In this study, we investigated a heterozygous in-frame duplication c.436_462dup p. (Pro146_Cys154dup) in the SQSTM1 gene in a family with a new phenotype characterized by a personality disorder and behavioral variant frontotemporal dementia (b...

Introduction and aim: COVID-19 pandemic has disturbed many hospital activities, including medical education. We describe the switch from in-person didactic sessions to videoconferencing in a Neurology department. We analyse the opinions and satisfaction of participants. Material and methods: Narrative description of the adopted measures; Online...

Resumen Introducción La inflamación relacionada con la angiopatía amiloide es una entidad caracterizada por una respuesta inflamatoria alrededor de los depósitos de beta amiloide de la microcirculación cerebral. Métodos Revisión retrospectiva de una serie de pacientes con inflamación relacionada con angiopatía amiloide, que cumplieran criterios c...

Amyloid positron emission tomography (PET) brain imaging with radiotracers like [¹⁸F]florbetapir (FBP) or [¹⁸F]flutemetamol (FMM) is frequently used for the diagnosis of Alzheimer’s disease. Quantitative analysis is usually performed with standardized uptake value ratios (SUVR), which are calculated by normalizing to a reference region. However, th...

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused predominantly by pathogenic variants in NOTCH3 gene. Neither germline nor somatic mosaicism has been previously published in NOTCH3 gene. CADASIL is inherited in an autosomal dominant manner; only rare cas...

Background The SORL1 gene encodes a type‐I transmembrane protein termed sortilin‐related receptor (SorLA). SorLA regulates the intracellular transport and processing of the amyloid precursor protein in neurons, and therefore, it has been implicated in the pathogenesis of Alzheimer’s disease (AD). Several SORL1 mutations have been described as a ris...

Background Efforts focused on developing new less invasive biomarkers for early Alzheimer’s disease (AD) diagnosis are substantial. Evidences of infectious pathogens in AD brains may suggest a deteriorated defensive system in AD pathology. Lactoferrin (Lf), one of the major antimicrobial peptides in saliva, is an important oral defensive system tha...

Purpose of Review to provide an updated analysis of the possible use of non-steroidal anti-inflammatory drugs (NSAIDs) as treatments for Alzheimer´s disease (AD). Recent Findings Neuroinflammation in AD is an active field of research, with increasing evidence from basic and clinical studies for an involvement of innate or adaptive immune responses...

We analyzed the frequency of cognitive impairment (CI) in deceased COVID-19 patients at a tertiary hospital in Spain. Among the 477 adult cases who died after admission from March 1 to March 31, 2020, 281 had confirmed COVID-19. CI (21.1% dementia and 8.9% mild cognitive impairment) was a common comorbidity. Subjects with CI were older, tended to l...

In Alzheimer’s disease (AD) amyloid-β (Aβ) deposits may cause impairments in choroid plexus, a specialised brain structure which forms the blood–cerebrospinal fluid (CSF) barrier. We previously carried out a mass proteomic-based study in choroid plexus from AD patients and we found several differentially regulated proteins compared with healthy sub...

Introduction: Little is known about the relation of cognitive impairment (CI) to COVID-19 mortality. Here, we analyse the frequency of CI in deceased COVID-19 patients. Methods: We included 477 adult cases that died after admission from March 1 to March 31, 2020: 281 with confirmed COVID-19, 58 probable COVID-19, and 138 who died of other causes. R...

The original version of this article unfortunately contained some mistakes.

Background Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients. Methods To assess the clinical utility of salivary Lf for AD diagnosis,...

Kynurenic acid (KYNA) is a product of the tryptophan (TRP) metabolism via the kynurenine pathway (KP). This pathway is activated in neurodegenerative disorders, such as Alzheimer´s disease (AD). KYNA is primarily produced by astrocytes and is considered neuroprotective. Thus, altered KYNA levels may suggest an inflammatory response. Very recently,...

Background Efforts focused on developing new less invasive biomarkers for early Alzheimer’s disease (AD) diagnosis are substantial. Evidences of infectious pathogens in AD brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary levels of Lf in AD patients, one of the major antimicrob...

Background: To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer's disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (Aβ) levels with the presence of pathological accumulation of Aβ in the brain measured by amyloid-PET. B...

Introduction: Chronic traumatic encephalopathy (CTE) is a tauopathy associated to repetitive head trauma. There are no validated in vivo biomarkers of CTE and a definite diagnosis can only be made at autopsy. Recent studies have shown that positron emission tomography (PET) tracer AV-1451 (Flortaucipir) exhibits high binding affinity for paired he...

Hereditary cerebral amyloid angiopathies (CAA) are rare disorders of early onset and severe course. We describe a 47-year-old patient with Iowa-type amyloid precursor protein (APP) mutation-related hereditary CAA that manifested with concomitant lobar hemorrhage and venous sinus thrombosis. To analyze the cerebral amyloid-β burden, an amyloid-PET w...

Alzheimer disease (AD) mortality risk in a large cohort of subjects treated or not with non-steroidal anti-inflammatory drugs (NSAIDs) is unknown. Our objective was to determine whether NSAIDs use is associated with decreased risk of AD mortality. In this prospective, population-based study (Neurological Disorders in Central Spain [NEDICES]) of 5,0...

Positron emission tomography (PET) with amyloid binding tracers and 18F-fluordesoxyglucose (FDG) is used in the diagnosis of Alzheimer’s disease and other dementias. The dual-phase amyloid PET protocol acquires an early perfusion image immediately after the radiotracer injection that resembles FDG images. We studied the correlation of early phase 1...

Introduction Knowledge of the socioeconomic impact of dementia-related disorders is essential for appropriate management of healthcare resources and for raising social awareness. Methods We performed a literature review of the published evidence on the epidemiology, morbidity, mortality, associated disability and dependence, and economic impact of...

Semantic variant primary progressive aphasia (svPPA) is a clinical syndrome included in the frontotemporal dementia (FTD) spectrum. Unlike other forms of FTD, it is sporadic in the majority of cases and not commonly associated with motor neuron disease (MND). We describe a case of svPPA associated with MND in the same family, due to a mutation of t...

Background: Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive deterioration of language. Being rare, reports of PPA in multilingual individuals are scarce, despite more than half of the world population being multilingual. Methods: We describe clinical characteristics of 33 bilingual patients with PPA...

Platelets are considered a good model system to study a number of elements associated with neuronal pathways as they share biochemical similarities. Platelets represent the major source of amyloid-β (Aβ) in blood contributing to the Aβ accumulation in the brain parenchyma and vasculature. Peripheral blood platelet alterations including cytoskeletal...

Objective: We investigated the mortality rates of three subtypes of disability and their specific explanatory factors in older adults. Methods: Our data come from NEDICES, a population-based longitudinal cohort study of Spanish older adults. We examined 3816 participants without dementia who completed the Pfeffer's Functional Activities Questionnai...

BACKGROUND The Neurological Disorders in Central Spain, second survey (NEDICES-2) is a population-based, closed-cohort study that will include over 8000 subjects aged ≥55 years. It will also include a biobank. OBJECTIVE The objective of this study was to evaluate all major aspects of the NEDICES-2 (methods, database, screening instruments, and que...

Objective To report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody‐negative after a comprehensive immunological study. Methods Review of clinical records of 163 patients with LE. Immunohistochemistry on rat brain, cultured neurons, and cell‐based assays were used to identify neuronal autoantibodies. Pat...

The SORL1 gene encodes a protein involved in the amyloidogenic process, and its variants have been associated with Alzheimer’s disease (AD) physiopathology. We screened for SORL1 variants in 124 familial (44 early- and 80 late-onset) dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes (three not previously reported and six r...

We present a 86-year-old woman without relevant medical history and two brothers who died by dementia, who started at 55 years with depression and personality changes with ongoing worsening (>30 years) and functional decline. Screening dementia blood test and brain magnetic resonance imaging did not show results that pointed to a secondary cause. T...

Introduction: Knowledge of the socioeconomic impact of dementia-related disorders is essential for appropriate management of healthcare resources and for raising social awareness. Methods: We performed a literature review of the published evidence on the epidemiology, morbidity, mortality, associated disability and dependence, and economic impac...

OBJECTIVE: We investigated whether educational attainment influences the cognitive trajectories of older adults with different dementia subtypes. METHODS: All participants were selected from NEDICES, a prospective population-based cohort study of Spanish older adults. A total sample of 53 individuals with dementia completed the MMSE-37 at Times 1...

Currently there are different tools based on Luria’s neuropsychological assessment approach, but empirical data on Spanish popula-tions are limited. The main objective of this study is to review scientific evidences about the psychometric properties of the Luria Spa-nish Battery Neuropsychological Diagnosis in adults (Luria DNA) but empirical data...

Introduction The Alzheimer's disease (AD) process is likely initiated many years before clinical onset. Biomarkers of preclinical disease are critical for the development of disease-modifying or even preventative therapies. Current biomarkers for early disease, including cerebrospinal fluid tau and amyloid β (Aβ) levels, structural and functional m...

Objective: We aimed to analyse the clinical utility of the Mattis Dementia Rating Scale (MDRS-2) for early detection of Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) in a sample of Spanish older adults. Methods: A total of 125 participants (age = 75.12 ± 6.83, years of education =7.08 ± 3.57) were classified in three diag...

The immunosuppressant tacrolimus (FK506) is widely used in transplantation medicine. An acute leukoencephalopathy with clinical and radiologic features similar to posterior reversible encephalopathy syndrome (PRES) is a common side effect of tacrolimus, and usually develops within the first year of commencing treatment,¹ but a delayed and chronic l...

Primary progressive aphasia (PPA) is considered a heterogeneous syndrome, with different clinical subtypes and neuropathological causes. Novel PET biomarkers may help to predict the underlying neuropathology, but many aspects remain unclear. We studied the relationship between amyloid PET and PPA variant in a clinical series of PPA patients. A syst...

Background Essential tremor (ET) and Parkinson’s disease (PD) are two of the most common movement disorders. Leaving aside their motor features, these two conditions share several non-motor features, including cognitive dysfunction and personality changes. However, there are few data comparing the cognitive and personality profiles of ET with PD. H...

To analyze whether Physical activity (PA) reduces mortality risk at thirteen years' follow-up in a population-based cohort of Spanish older adults. The NEDICES (Neurological Disorders in Central Spain) is a prospective population-based survey of older adults (age≥65years) that comprised 5278 participants at baseline. A modified version of the Rosow...

Background: The effect of different educational indices on clinical diagnosis of dementia requires more investigation. Objective: We compared the differential influence of two educational indices (EIs): years of schooling and level of education (i.e., null/low literacy, can read and write, primary school, and secondary school) on global cognitio...

Background: To assess the diagnostic agreement of cognitive status (dementia, mild cognitive impairment (MCI), normal cognition) among neurologists in the field of neurological disorders in Central Spain 2 study. Methods: Full medical histories of 30 individuals were provided to 27 neurologists: 9 seniors, 10 juniors and 8 residents. For each ca...

This review proposes a more optimistic view of Alzheimer's disease (AD), in contrast to that contributed by the ageing of the population and the failure of potentially curative therapies (vaccines and others). Treatment failure is likely due to the fact that AD gestates in the brain for decades but manifests in old age. This review updates the conc...

This review proposes a more optimistic view of Alzheimer's disease (AD), in contrast to that contributed by the ageing of the population and the failure of potentially curative therapies (vaccines and others). Treatment failure is likely due to the fact that AD gestates in the brain for decades but manifests in old age. This review updates the conc...

Introduction: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. Development: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take l...

Descriptive report of the variant adult visceral form non-neuronopathic of Νiemann-Ρick type C disease in a Spanish series

Background The predictive value of diverse subtypes of mild cognitive impairment (MCI) for dementia and death is highly variable. Objective To compare the predictive value of several MCI subtypes in progression to dementia and/or mortality in the NEDICES (Neurological Disorders in Central Spain) elderly cohort. Methods Retrospect algorithmic MCI...

The aim of this study was to analyze whether physical activity (PA) is a protective factor for the incidence of dementia after 3 years of follow-up. The Neurological Disorders in Central Spain (NEDICES) is a prospective population-based survey of older adults (age 65 years and older) that comprised 5278 census-based participants at baseline (1994-1...

Early separation of mild cognitive impairment (MCI) from normal aging and mild cases of dementia remains a challenge, especially in the general population. We aimed to analyze the diagnostic accuracy of a brief neuropsychological battery (BNB) in dementia and MCI cases from the Neurological Disorders in Central Spain (NEDICES) population-based coho...

Introduction: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in theclinical setting. Several BCT have been developed and/or validated in our country, but we lackspecific recommendations for use. Development: Review of studies on the diagnostic accuracy of BCT for CI, using studies conduc-ted in Spain with BCT which take less...

Megalin or low-density lipoprotein receptor related protein-2 (LRP-2) is a member of the low-density lipoprotein (LDL) receptor family which has been linked to Alzheimer’s disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood-cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from c...

Essential tremor (ET), a highly-prevalent, progressive, aging-associated neurological disease, poses a significant public health challenge. Aside from its associated motor features, the disease affects cognition in some patients, mood, and morale, and has been associated with increased risk of mortality in the elderly. Studies have not investigated...

Studies investigating the association between hypercholesterolemia in the elderly and cognitive decline report discrepant outcomes. We determined in a prospective population-based cohort (NEDICES) in elders whether hypercholesterolemia was associated with slower cognitive decline. Participants were evaluated at baseline and 3years later. Baseline d...

A 56-year-old woman presented to the emergency department with sudden onset of left-sided ptosis, perioral paraesthesias and dizziness, without imbalance or vertigo, after getting up from bed. She had hyperlipidaemia and was a smoker. General examination was normal. On neurological examination there was asymmetric bilateral ptosis, more on the left...

Dear Sirs,Amyloidosis is a heterogeneous group of diseases characterized by the extracellular deposition of an amorpho us material, composed of insoluble fibrillar proteins. Cerebral amyloidoma is a type of localized amyloidosis that can rarely affect the brain, with around 30 cases described in the literature [1-5].Florbetapir is an amyloid radiol...