Ana Baena

Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease

Importance It is critically important to improve our ability to diagnose and track Alzheimer disease (AD) as early as possible. Individuals with autosomal dominant forms of AD can provide clues as to which and when biological changes are reliably present prior to the onset of clinical symptoms. Objective To characterize the associations between amyloid and tau deposits in the brains of cognitively unimpaired and impaired carriers of presenilin 1 (PSEN1) E280A mutation. Design, Setting, and Participants In this cross-sectional imaging study, we leveraged data from a homogeneous autosomal dominant AD kindred, which allowed us to examine measurable tau deposition as a function of individuals’ proximity to the expected onset of dementia. Cross-sectional measures of carbon 11–labeled Pittsburgh Compound B positron emission tomography (PET) and flortaucipir F 18 (previously known as AV 1451, T807) PET imaging were assessed in 24 PSEN1 E280A kindred members (age range, 28-55 years), including 12 carriers, 9 of whom were cognitively unimpaired and 3 of whom had mild cognitive impairment, and 12 cognitively unimpaired noncarriers. Main Outcomes and Measures We compared carbon 11–labeled Pittsburgh Compound B PET cerebral with cerebellar distribution volume ratios as well as flortaucipir F 18 PET cerebral with cerebellar standardized uptake value ratios in mutation carriers and noncarriers. Spearman correlations characterized the associations between age and mean cortical Pittsburgh Compound B distribution volume ratio levels or regional flortaucipir standardized uptake value ratio levels in both groups. Results Of the 24 individuals, the mean (SD) age was 38.0 (7.4) years, or approximately 6 years younger than the expected onset of clinical symptoms in carriers. Compared with noncarriers, cognitively unimpaired mutation carriers had elevated mean cortical Pittsburgh Compound B distribution volume ratio levels in their late 20s, and 7 of 9 carriers older than 30 years reached the threshold for amyloidosis (distribution volume ratio level > 1.2). Elevated levels of tau deposition were seen within medial temporal lobe regions in amyloid-positive mutation carriers 6 years before clinical onset of AD in this kindred. Substantial tau deposition in the neocortex was only observed in 1 unimpaired carrier and in those with mild cognitive impairment. &bgr;-Amyloid uptake levels were diffusely elevated in unimpaired carriers approximately 15 years prior to expected onset of mild cognitive impairment. In carriers, higher levels of tau deposition were associated with worse performance on the Mini-Mental State Examination (entorhinal cortex: r = −0.60; P = .04; inferior temporal lobe: r = −0.54; P = .06) and the Consortium to Establish a Registry for Alzheimer Disease Word List Delayed Recall (entorhinal cortex: r = −0.86; P < .001; inferior temporal lobe: r = −0.70; P = .01). Conclusions and Relevance The present findings add to the growing evidence that molecular markers can characterize biological changes associated with AD in individuals who are still cognitively unimpaired. The findings also suggest that tau PET imaging may be useful as a biomarker to distinguish individuals at high risk to develop the clinical symptoms of AD and to track disease progression.

ENTORHINAL TAU PATHOLOGY IS ASSOCIATED WITH WHITE MATTER ABNORMALITIES IN UNCINATE FASCICULUS IN PRECLINICAL AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE

familiar objects”) was associated with EC tau (r1⁄40.317, p1⁄40.018) and item 13 (“Making decisions about everyday matters”) was associated with ITL tau (r1⁄40.296, p1⁄40.028). Conclusions: A mixture of language, executive function, and memory informant concerns as well as memory and executive self-concerns were most strongly associated with tau deposition. These findings suggest that concerns across both memory and non-memory domains are important markers of pathology. Given that the CCI-20 is relatively short and easy to administer, this measure may be useful to include in future studies. References: [1] Buckley et al. (2017) JAMA Neurology. [2] Jessen et al. (2010) Arch Gen Psychiatry.

TAU ACCUMULATION IN THE ENTORHINAL CORTEX AND PRECUNEUS IS ASSOCIATED WITH CORTICAL AMYLOID-BETA BURDEN, AGE AND WORSE MEMORY PERFORMANCE IN PRECLINICAL AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE

P4-299 TAU ACCUMULATION IN THE ENTORHINAL CORTEX AND PRECUNEUS IS ASSOCIATEDWITH CORTICAL AMYLOID-BETA BURDEN, AGE AND WORSE MEMORY PERFORMANCE IN PRECLINICAL AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE Yakeel T. Quiroz, Reisa A. Sperling, Francisco Lopera, Ana Baena, Sergio Alvarez, Edmarie Guzman-Velez, Enmanuelle Pardilla-Delgado, Joseph Arboleda-Velasquez, Jennifer R. Gatchel, Joshua Fuller, Arabiye Artola, Aaron P. Schultz, Kewei Chen, Pierre N. Tariot, Eric M. Reiman, Keith A. Johnson, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA; Center for Alzheimer Research and Treatment, Brigham andWomen’s Hospital, Harvard Medical School, Boston, MA, USA; Grupo de Neurociencias, Universidad de Antioquia, Medellin, Colombia; Hospital Pablo Tobon Uribe, Medellin, Colombia; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Schepens Eye Research Institute, Boston, MA, USA; HarvardMedical School, Boston, MA, USA; Banner Alzheimer’s Institute, Phoenix, AZ, USA; Department of Radiology, Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Boston, MA, USA. Contact e-mail: yquiroz@mgh.harvard.edu

TAU ACCUMULATION IN RHINAL CORTEX IS ASSOCIATED WITH MEMORY PERFORMANCE IN NON-DEMENTED YOUNG ADULTS WITH AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE

P2-452 TAUACCUMULATION INRHINALCORTEX IS ASSOCIATEDWITH MEMORY PERFORMANCE IN NONDEMENTED YOUNG ADULTS WITH AUTOSOMAL DOMINANTALZHEIMER’S DISEASE Justin S. Sanchez, Reisa A. Sperling, Francisco Lopera, Jean Augustinack, Alex Becker, Heidi IL. Jacobs, David Jin, Samantha Katz, Evelyn Luner, Kirsten Moody, Julie C. Price, Edmarie Guzman-Velez, Ana Baena, Enmanuelle Pardilla-Delgado, Kewei Chen, Eric M. Reiman, Keith A. Johnson, Yakeel T. Quiroz, Massachusetts General Hospital, Boston, MA, USA; Center for Alzheimer Research and Treatment, Brigham andWomen’s Hospital, Harvard Medical School, Boston, MA, USA; Grupo de Neurociencias, Universidad de Antioquia, Medellin, Colombia; Massachusetts General Hospital, Charlestown, MA, USA; Alzheimer Center Limburg, Maastricht University, Maastricht, Netherlands; University of Pittsburgh, Pittsburgh, PA, USA; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; University of Arizona, Tucson, AZ, USA; Arizona Alzheimer’s Consortium, Phoenix, AZ, USA; Department of Radiology, Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA. Contact e-mail: justin.sanchez@mgh. harvard.edu

TAU ACCUMULATION AND MEMORY DECLINE ARE MORE CLOSELY RELATED TO STRIATAL THAN CORTICAL AMYLOIDOSIS IN INDIVIDUALS WITH EARLY-ONSET AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE

GDS-slope, amyloid, GDS-slope X amyloid, and the covariates above. Results:In the model with baseline GDS, sex (p1⁄40.0005; females with higher scores), higher age (p<0.0001), lower education (p<0.0001), and amyloid X time (p1⁄40.0088; greater amyloid associated with greater PACC decline) were significant, but baseline GDS did not predict PACC decline. In the model with GDS-slope, higher age (p<0.0001), lower education (p1⁄40.03) and GDS-slope X amyloid (p1⁄40.0002) significantly predicted PACC decline, such that increasing GDS scores with baseline amyloid were associated with greater PACC decline. In secondary analyses holding time and all other predictors constant, longitudinally increasing GDS predicted decreasing PACC in those with amyloid levels above 1.10. Conclusions:Results suggest that worsening depressive symptoms in the setting of elevated amyloid are associated with cognitive decline. While future work is needed to determine causality, findings support the potential prognostic utility of depressive symptoms in identifying older adults at risk for cognitive decline and AD.

Cambios en el EEG en reposo de exparticipantes en el conflicto armado colombiano con trastorno de personalidad antisocial

INTRODUCTION Although the social and economic consequences of Colombian internal conflicts mainly affected the civilian population, they also had other implications. The ex-combatants, the other side of the conflict, have been the subject of many studies that question their personality structures and antisocial features. Results suggest that ex-combatants usually have characteristics of an antisocial personality disorder (ASPD) that is related with their behaviour. METHODS Quantitative EEG (qEEG) was used to evaluate differences in cortical activity patterns between an ex-combatants group and a control group. The Psychopathy Checklist-Revised (PCL-R) was used to assess the presence of ASPD in the ex-combatants group, as well as the Diagnostic Interview for Genetic Studies (DIGS) for other mental disorders classified in the DCI-10. RESULTS There are significant differences in psychopathy levels between groups, as well as in alpha-2 and beta waves, especially in left temporal and frontal areas for alpha-2 waves and left temporal-central regions for beta waves. CONCLUSIONS qEEG measurements allow spectral resting potential to be differentiated between groups that are related with features typically involved in antisocial personality disorder, and to correlate them with patterns in the questionnaires and clinical interview.

Precuneus failures in subjects of the PSEN1 E280A family at risk of developing Alzheimer's disease detected using quantitative electroencephalography

BACKGROUND Presenilin-1 (PSEN1) mutations are the most common cause of familial early onset Alzheimers disease (AD). The PSEN1 E280A (E280A) mutation has an autosomal dominant inheritance and is involved in the production of amyloid-β. The largest family group of carriers with E280A mutation is found in Antioquia, Colombia. The study of mutation carriers provides a unique opportunity to identify brain changes in stages previous to AD. Electroencephalography (EEG) is a low cost and minimally invasiveness technique that enables the following of brain changes in AD. OBJECTIVE To examine how previous reported differences in EEG for Theta and Alpha-2 rhythms in E280A subjects are related to specific regions in cortex and could be tracked across different ages. METHODS EEG signals were acquired during resting state from non-carriers and carriers, asymptomatic and symptomatic subjects from E280A kindred from Antioquia, Colombia. Independent component analysis (ICA) and inverse solution methods were used to locate brain regions related to differences in Theta and Alpha-2 bands. RESULTS ICA identified two components, mainly related to the Precuneus, where the differences in Theta and Alpha-2 exist simultaneously at asymptomatic and symptomatic stages. When the ratio between Theta and Alpha-2 is used, significant correlations exist with age and a composite cognitive scale. CONCLUSION Theta and Alpha-2 rhythms are altered in E280A subjects. The alterations are possible to track at Precuneus regions using EEG, ICA, and inverse solution methods.

ANXIETY, SUBJECTIVE COGNITIVE DECLINE, AND CORTICAL AMYLOID IN PRECLINICAL AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE: A PRELIMINARY REPORT

Common scanner models reported by ADNI MRI scanning sites. ADNI site selection is driven by the ability of a site to recruit study subjects. Scanner prevalence in ADNI should not be considered as indicative of the overall distribution of MRI scanners in production. Scanners with 70cm bores may have relatively slow gradients making diffusion imaging unworkably long for the limited total time available for ADNI imaging.ManyGE750 systems do not have sufficient head coils to support SMS. As of early 2017 some sites still do not have a scanner which has been chosen for use in ADNI-3

TAU AND AMYLOID PET IMAGING IN A COLOMBIAN KINDRED WITH AUTOSOMAL-DOMINANT ALZHEIMER'S DISEASE

was performed on 193 clinically normal (CN) and 36 cognitively impaired, AD-pathway-PiB+ participants (12 amnestic MCI, 24 AD). AV-1451 cortical-to-crus grey matter ratios (SUVr) by regions-of-interest (ROIs) were measured. Regional tau-PET diagnostic separability between CN and impaired groups (area-underthe-ROC-curve [AUROC]), voxel-based CN vs. impaired group differences, and clustering of all individuals on regional Tau-PET SUVr were each assessed. ROIs were ranked by Tau-PET abnormality, based on the number of CN participants with Tau-PET SUVr above the 95 percentile of CN<55yr. Associations between neuropsychological tests and AV-1451 and PiB among CN were evaluated, adjusting for age, sex, and education. Results:AV-1451 separability of CN and impaired in typical AD regions was high (AUROC 0.9-1.0). Voxel analysis showed widespread AV-1451 signal in impaired vs CN, most prominently in the temporal lobe, precuneus and posterior cingulate (Figure 1). There was a weak positive association between AV-1451 uptake and age in CN but a negative association in impaired. Clustering of participants on regional AV-1451 values demonstrated associated subsets as follows: CN, early tauopathy, early-age onset and late-age onset AD. Among CN, angular, occipital, posterior and middle cingulate, middle temporal, fusiform, lingual and precuneus in addition to medial temporal ROIs were identified as the ROIs with the most abnormal AV-1451 SUVr values (Figure 2). No significant associations with AV-1451 or PiB and memory, attention, language, visuospatial, or global z-scores were seen in CNs after adjusting for age, sex, and education. Conclusions:Tau-PETwith AV-1451 generally supports the Braak staging sequence of tau deposition in the AD dementia pathway (spread from medial temporal to basal temporal to other association corticial areas) with some important additions. Clustering identified subsets of participants with associated AV-1451 regional findings. No significant neuropsychologic associations with tau were seen in CNs. AV-1451 signal in CNs may suggest subclinical, early AD-pathology tau or primary age-related tauopathy.

FACE-NAME RECOGNITION MEMORY IN PRECLINICAL AUTOSOMAL-DOMINANT ALZHEIMER’S DISEASE: AN FMRI STUDY

moderate [Odds Ratios (OR): 3