Edmarie Guzman-Velez

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 levelu2009>u20091.2). 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: ru2009=u2009−0.60; Pu2009=u2009.04; inferior temporal lobe: ru2009=u2009−0.54; Pu2009=u2009.06) and the Consortium to Establish a Registry for Alzheimer Disease Word List Delayed Recall (entorhinal cortex: ru2009=u2009−0.86; Pu2009<u2009.001; inferior temporal lobe: ru2009=u2009−0.70; Pu2009=u2009.01). 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.

A novel two-day intervention reduces stress in caregivers of persons with dementia

Caregivers of individuals with dementia are at heightened risk for stress‐related mental and physical illnesses, and this problem is growing. There is a critical need to develop effective interventions for caregivers. This study tested whether a 2‐day intervention improved psychological health in caregivers of individuals with dementia.

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

SOCIOCULTURAL FACTORS AND COGNITIVE IMPAIRMENT IN OLDER LATINOS LIVING IN BOSTON

Background: Global initiatives for Alzheimer’s disease (AD) need cognitive screening tools that hold global reliability. Such tools would allow screening for dementia in ageing populations across countries with different socio-demographic structures. Psychometric tests have for long faced the negative impact of confounding factors such as education, age and ethnicity, which have proved difficult to fully control for. A recently developed temporary memory binding test appears to overcome these limitations. Here we present global data collected with the Short-Term Memory Binding Test (STMBT) to support the hypothesis that the cognitive construct underlying temporary binding remains stable across populations with different socio-demographic backgrounds. Methods:We present data from 293 subjects (142 healthy controls and 151 patients with AD dementia) who have performed the STMBT following procedures harmonized across countries. We show data from 6 countries (Brazil, Italy, Colombia, Romania, Spain, and the UK) which have very different socio-cultural backgrounds. The STMBT requires participants to detect whether or not two combinations of shape and colour change across two sequential arrays. The percentage of correct recognition is measured along with other neuropsychological variables. Results: Significant temporary binding deficits are found in all the AD samples (Figure 1). Such samples significantly differed in age (F(5,287)1⁄4126.22, p < 0.001) and education (F(5,287)1⁄4 11.89, p < 0.001). However, neither factor accounted for the effect of Group (F(1,228)1⁄4238.16, p < 0.001) or modified the Group x Country interaction, which failed to meet the significance threshold (F(4,228)1⁄42.38, p1⁄40.06). Education was excluded from a step-wise regression model which retained the STMB score as the main Group predictor (i.e., total adjusted R: 59.4% -F(3,288)1⁄4142.86, p<0.001-; STMB: 54.7% -F(1,290)1⁄4352.2, p<0.001-, Country contributed only 2% and Age 3% of the explained variance). Conclusions:A simple, quick, and easy to administer test which can be applied using computers or flash cards is providing solutions that can meet the needs of global dementia strategies. STMB reveals the presence of AD in pre-symptomatic or in early symptomatic stages. It has helped differentiate AD form other non-AD dementias. Thus, STMB is a transcultural cognitive marker of AD.