Carolina Minguillon

The ALFA project: A research platform to identify early pathophysiological features of Alzheimer's disease

The preclinical phase of Alzheimers disease (AD) is optimal for identifying early pathophysiological events and developing prevention programs, which are shared aims of the ALFA project, including the ALFA registry and parent cohort and the nested ALFA+ cohort study.

Alzheimer’s disease prevention: from risk factors to early intervention

Due to the progressive aging of the population, Alzheimer’s disease (AD) is becoming a healthcare burden of epidemic proportions for which there is currently no cure. Disappointing results from clinical trials performed in mild–moderate AD dementia combined with clear epidemiological evidence on AD risk factors are contributing to the development of primary prevention initiatives. In addition, the characterization of the long asymptomatic stage of AD is allowing the development of intervention studies and secondary prevention programmes on asymptomatic at-risk individuals, before substantial irreversible neuronal dysfunction and loss have occurred, an approach that emerges as highly relevant.In this manuscript, we review current strategies for AD prevention, from primary prevention strategies based on identifying risk factors and risk reduction, to secondary prevention initiatives based on the early detection of the pathophysiological hallmarks and intervention at the preclinical stage of the disease. Firstly, we summarize the evidence on several AD risk factors, which are the rationale for the establishment of primary prevention programmes as well as revising current primary prevention strategies. Secondly, we review the development of public–private partnerships for disease prevention that aim to characterize the AD continuum as well as serving as platforms for secondary prevention trials. Finally, we summarize currently ongoing clinical trials recruiting participants with preclinical AD or a higher risk for the onset of AD-related cognitive impairment.The growing body of research on the risk factors for AD and its preclinical stage is favouring the development of AD prevention programmes that, by delaying the onset of Alzheimer’s dementia for only a few years, would have a huge impact on public health.

Incidental findings on brain MRI of cognitively normal first-degree descendants of patients with Alzheimer's disease: a cross-sectional analysis from the ALFA (Alzheimer and Families) project

Objectives To describe the prevalence of brain MRI incidental findings (IF) in a cohort of cognitively normal first-degree descendants of patients with Alzheimers disease (AD). Design Cross-sectional observational study. Setting All scans were obtained with a 3.0 T scanner. Scans were evaluated by a single neuroradiologist and IF recorded and categorised. The presence of white matter hyperintensities (WMH) was determined with the Fazekas scale and reported as relevant if ≥2. Participants 575 participants (45–75 years) underwent high-resolution structural brain MRI. Participants were cognitively normal and scored over the respective cut-off values in all the following neuropsychological tests: Mini-Mental State Examination (≥26), Memory Impairment Screen (≥6), Time Orientation Subtest of the Barcelona Test II (≥68), verbal semantic fluency (naming animals ≥12). Clinical Dementia Rating (CDR) had to be 0. Results 155 participants (27.0%) presented with at least one IF. Relevant WMH were present in 7.8% of the participants, and vascular abnormalities, cyst and brain volume loss in 10.7%, 3.1% and 6.9% of the study volunteers, respectively. Neoplastic brain findings were found in 2.4% of participants and within these, meningiomas were the most common (1.7%) and more frequently found in women. A positive correlation between increasing age and the presence of IF was found. Additionally, brain atrophy greater than that expected by age was significantly more prevalent in participants without a parental history of AD. Conclusions Brain MRIs of healthy middle-aged participants show a relatively high prevalence of IF even when study participants have been screened for subtle cognitive alterations. Most of our participants are first-degree descendants of patients with AD, and therefore these results are of special relevance for novel imaging studies in the context of AD prevention in cognitively healthy middle-aged participants. Trial registration number NCT02198586.

Effects of APOE-ε4 allele load on brain morphology in a cohort of middle-aged healthy individuals with enriched genetic risk for Alzheimer's disease

Apolipoprotein E (APOE)‐ε4 is the major genetic risk factor for Alzheimers disease. However, the dose‐dependent impact of this allele on brain morphology of healthy individuals remains unclear.

The Rationale Behind the New Alzheimer’s Disease Conceptualization: Lessons Learned During the Last Decades

In the last decades, progress in neuroimaging techniques and cerebrospinal fluid assays has enabled the characterization of several Alzheimer’s disease (AD) biomarkers. This knowledge has shifted the conceptualization of AD from a clinical-pathological construct, where its diagnosis required the presence of dementia with distinct pathologic features, toward a clinical-biological one that recognizes AD as a pathological continuum with a clinical picture that ranges from normal cognition to a dementia stage. Specifically, AD is now divided into three stages: preclinical (abnormal biomarkers and no or only subtle cognitive impairment), mild cognitive impairment or prodromal AD (abnormal pathophysiological biomarkers and episodic memory impairment), and dementia (abnormal biomarkers and clear cognitive and functional impairment). The possibility of assessing AD pathophysiology in vivo before the onset of clinical symptoms in the preclinical stage provides the unprecedented opportunity to intervene at earlier stages of the continuum in secondary prevention trials. Currently, large cohort studies of cognitively healthy participants are undergoing with the main aim of disentangling the natural history of AD to identify individuals with an increased risk of developing AD in the near future to be recruited in these clinical trials. In this paper, we review how the concept of AD has changed over the years as well as discuss the implications of this conceptual change.

INTERACTION BETWEEN AGE AND APOE GENOTYPE ON THE COGNITIVE PERFORMANCE OF HEALTHY INDIVIDUALS AT RISK FOR ALZHEIMER’S DISEASE

P3-550 INTERACTION BETWEEN AGE AND APOE GENOTYPE ON THE COGNITIVE PERFORMANCE OF HEALTHY INDIVIDUALSATRISKFORALZHEIMER’S DISEASE Marta Crous-Bou, Gonzalo S anchez-Benavides, Raffaele Cacciaglia, Nina Gramunt, Carolina Minguillon, Karine Fauria, Juan Domingo Gispert, Jos e Luis Molinuevo, Barcelonabeta Brain Research Center, Barcelona, Spain; Barcelonabeta Brain Research Center, Barcelona, Spain. Contact e-mail: mcrous@fpmaragall.org

IMPACT OF APOE GENETIC VARIANT ON BRAIN MORPHOLOGY IN A COHORT OF COGNITIVELY HEALTHY MIDDLE-AGED INDIVIDUALS WITH ENRICHED GENETIC RISK FOR ALZHEIMER’S DISEASE

526 middle-aged healthy adults. A) Mean-centered bar plots showing GM volumetric differences among the five APOE genotype groups. Spatial coordinates are given in the Montral Neurological Institute (MNI) standard space. B) Statistical parametric maps displaying main effects of APOE genotype on GM volumes. The bilateral hippocampus and thalamus are represented in cold and warm colors, respectively. Podium Presentations: Thursday, July 20, 2017 P1465