Kate V. Papp

Tau positron emission tomographic imaging in aging and early Alzheimer disease

Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis of Alzheimer disease (AD), staging and monitoring of disease progression, and development of disease‐modifying therapies.

Tau PET imaging in aging and early Alzheimer's disease

Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis of Alzheimer disease (AD), staging and monitoring of disease progression, and development of disease‐modifying therapies.

FDG metabolism associated with tau‐amyloid interaction predicts memory decline

The aim of this article was to evaluate in normal older adults and preclinical Alzheimers disease (AD) the impact of amyloid and regional tauopathy on cerebral glucose metabolism and subsequent memory decline.

TAU AND HIPPOCAMPAL VOLUME REFLECT DISTINCT PROCESSES IN PRECLINICAL ALZHEIMER’S DISEASE

cognitively normal (with CDR1⁄40) and 14 cognitively impaired (CDR> 0, 9 CDR 0.5, 3 CDR 1, and 2 CDR 2) participants were drawn from studies on aging at Washington University in St. Louis. Participants had one or more MRI sessions preceding a visit where they acquired both a MRI scan and underwent PET imaging with AV-1451, with mean follow-up from first MRI of 5.3 (sd 2.3) yrs. A subset (n1⁄4 93) also underwent florbetapir beta-amyloid imaging. MRIs were processed using FreeSurfer to generate mean cortical thickness in each region of interest (ROI). PET data was converted to standardized uptake value ratios (SUVRs) normalized to the cerebellum and partial volume corrected. Global tau burden was estimated by the mean SUVR from entorhinal cortex, amygdala, inferior temporal cortex, and lateral occipital cortex ROIs. For each person, a slope estimating structural atrophy in each ROI was quantified by fitting all longitudinal MRI measurements in a generalized linear model (GLM). These slope estimates were then used to predict tau burden in a GLMwhile controlling for baseline age and gender. Participants who also had beta-amyloid imaging were fit into a second GLM, with an additional covariate of florbetapir mean cortical SUVR. Multiple comparisons were controlled using a false discovery rate. Results:Antecedent cortical thinning was significantly associated with tau deposition throughout the cortex in the entire cohort (Figure 1). The effects were most prominent in the lateral temporal lobe and inferior parietal areas. These associations remained even after controlling for florbetapir levels (Figure 2) and were evident even in cognitively normal cohorts alone (Figure 3). Conclusions:Antecedent cortical thinning predicts current PET Tau in preclinical AD and symptomatic AD. This relationship holds in AD even after controlling for PET beta-amyloid burden. This may be useful for participant selection for tau PET imaging or clinical trials.

THE IMPACT OF ANOSOGNOSIA AND ANOSODIAPHORIA ON THE PREDICTION OF PROGRESSION FROM MILD COGNITIVE IMPAIRMENT TO ALZHEIMER’S DISEASE

involved in self-referential processes as well as functional disconnection between these regions (Perrotin et al. 2015). The present study aims at extending these findings by better understanding the neural correlates of anosognosia in the prodromal stage of AD. Thus, here we used regional brain metabolism [FDG-PET] to unravel the metabolic correlates of anosognosia in patients with amnestic mild cognitive impairment (aMCI) and subsequently resting state fMRI [rs-fMRI] to investigate the intrinsic connectivity disruption between brain regions. Methods: Thirty-one subjects (mean age: 74.1; CDR: 0.5) with aMCI were included. All subjects underwent resting state 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) for glucose metabolism measurement and resting state fMRI for intrinsic connectivity measurement. An anosognosia index was obtained by calculating discrepancy scores between subjective and objective memory scores. Voxelwise correlations between anosognosia and neuroimaging data were conducted. All analyses were controlled for multiple comparison using pFDR 1⁄40.05. Results: Anosognosia in aMCI patients correlated with reduced glucose metabolism in posterior cingulate (PCC) cortices and hippocampus (Figure 1). Intrinsic connectivity analyses revealed a significant association between anosognosia and attenuated functional connectivity between the PCC seed region and orbitofrontal cortex (OFC) as well as bilateral inferior parietal lobes (IPL, Figure 2). Conclusions: These findings provide further evidence implicating cortical midline structures involved in awareness of memory deficits. MCI patients with anosognosia showed reduced metabolism as well as disconnection between OFC, PCC and hippocampus, brain regions vulnerable to changes in early Alzheimer’s disease, and therefore could be at increased risk of developing dementia. O4-06-05 MCI DIAGNOSIS: LESS IS MORE Liesbeth Aerts, John D. Crawford, Nicole A. Kochan, Megan Heffernan, Brian Draper, Julian N. Trollor, Perminder S. Sachdev, Henry Brodaty, Dementia Collaborative Research Centre, University of New SouthWales, Sydney, Australia; 2 Centre for Healthy Brain Ageing, UNSW, Sydney, Australia; 3 Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, Australia; Academic Department for Old Age Psychiatry, Prince of Wales Hospital, Randwick, Australia; 5 Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, Australia; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; 7 University of New South Wales, Sydney, Australia; 8 Centre for Healthy Brain Ageing UNSW Australia, Sydney, Australia; Dementia Collaborative Research Centre ABC, UNSWAustralia, Sydney, Australia. Contact e-mail: l.aerts@unsw.edu.au

COGNITIVE RESERVE RELATES TO GREATER FUNCTIONAL CONNECTIVITY AND STRONGER INTERCONNECTIVITY WITHIN AND BETWEEN NODES, INDEPENDENT OF β-AMYLOID: FINDINGS FROM THE HARVARD AGING BRAIN STUDY

reserve (CR) and an individual with low CR. The individual with high CR has a higher premorbid level of cognitive functioning, and is able to maintain this premorbid level at more advanced levels of neuropathology. However, once both individuals have reached their inflection point (i.e. the onset of cognitive decline), clinical progression from a certain level of cognition function will be faster for the individual with high CR. The blue area reflects the estimated interval in which baseline and follow up measurements were obtained from the pre-dementia subjects in our sample. Modified version of figure 1 from The Lancet Neurology, 11(11), by Y. Stern, “Cognitive reserve in ageing and Alzheimer’s disease” (2012), 1006-1012, with permission from Elsevier. Podium Presentations: Monday, July 17, 2017 P582

THE RELATIONSHIP BETWEEN RECALL OF RECENTLY VERSUS REMOTELY ENCODED FAMOUS FACES AND AMYLOID AND TAU BURDEN IN CLINICALLY NORMAL OLDER ADULTS

covariates.Models included all participants so thatWMH/cognition relationships could be explored independently from diagnostic category. Results:Right dorsolateral WMH volumes were negatively associated with Rey copy score (b1⁄4-2.6, p<.001); left dorsolateral WMH volumes were negatively associated with WCST total correct trials (b1⁄40.9, p1⁄4.036). Post-hoc analyses showed that WMH/Rey associations were driven primarily by AD participants, whileWMH/WCSTassociations were driven by CIND participants. Conclusions:Results indicate that not all executive functions are affected equally by SVD, and regional distribution of WMH may be selectively associated with different tests. Determining specific associations between SVD/executive processes at different stages of AD is the first step in developing targeted process-specific treatments, which may improve other areas of cognition downstream. This study increases understanding of brain-behavior relationships in SVD, a potentially modifiable risk factor for dementia, in the context of cognitive symptoms in persons with or at risk for AD.

HETEROGENEITY IN NEUROIMAGING PATTERNS PRESENT THROUGHOUT THE CLINICAL SPECTRUM OF TYPICAL LATE-ONSET AMNESTIC AD

Here, we studied the cognitive and emotional effectiveness of caregiver-implemented musical activities in persons with mild-moderate dementia (PWDs). Methods: In a three-arm randomized controlled trial (RCT), 89 PWD-caregiver dyads received a 10week singing intervention, a 10-week music listening intervention, or a usual care. Outcomewas assessed with neuropsychological tests and questionnaires on mood, quality of life (QOL) and caregiver burden at baseline, after the intervention (3-month stage, n 1⁄4 84), and 6 months later (9-month stage, n 1⁄4 74). Results:Compared to usual care, both singing and music listening enhanced general cognition and executive function and reduced depression at 3 months and enhanced orientation and autobiographical memory at 9 months. Singing also enhanced working memory at 3 months as well as reduced caregiver burden at 9 months. The positive effects of singing on working memory and of both musical activities on mood were larger in mild vs. moderate dementia. The musical background of the PWD did not influence the efficacy of the music interventions. Conclusions:PWD-caregivermusical activities have long-term cognitive, emotional, and social benefits in PWDs and could potentially be widely used in dementia care and rehabilitation.

LONGITUDINAL PEFORMANCE ON THE PRECLINICAL ALZHEIMER’S COGNITIVE COMPOSITE (PACC) IN SUBJECTS WITH BIOMARKER-DEFINED PRECLINCAL AD

“false positives” in amyloid imaging is subtle; for example, cognitively normal individuals may have brain Ab, and the presence of a positive amyloid scan does not mean that other important pathology is absent (i.e., multiple pathological causes of dementia). With regard to tau imaging, still in its infancy, it seems that the distribution of the radiotracer is more informative than is the distribution of an amyloid PET tracer. From both preexisting clinical-pathological data and the limited PET studies available, medial temporal lobe tau accumulation may not necessarily reflect the presence of AD. It seems that cognitive dysfunction and signs of brain degeneration may be more detectable as tau deposition is found in neocortex. Thus, both the sensitivity and specificity of tau as a biomarker of AD (in clinical or preclinical stages) is dependent on its location. Sensitivity and specificity, in this situation, may be more complex than a single scalar threshold. Finally, tau PET data may be complicated by binding of ligands to unusual sites such as the choroid plexus, brainstem, and basal ganglia. Conclusions:Although the availability of amyloidand tau-PET have greatly improved the characterization of the continuum of AD, a number of situations may arise in which PET data interpretation may be complex or ambiguous.

ASSOCIATIONS BETWEEN AMYLOIDOSIS AND LONGITUDINAL COGNITIVE DECLINE IN CLINICALLY NORMAL OLDER ADULTS

positives had 10-15% more often low memory and low MMSE scores than amyloid negatives at any age.Male sex, low educational level and APOE-e4 carriership increased the frequency of low memory and low MMSE scores independent of amyloid status. Conclusions:Amyloid pathology was already associated with low memory performance in individuals with normal cognition and alsowith lowMMSE score in patients withMCI. This was independent of sex, educational level and APOE-e4 carrier status. These results shed light on the temporal relationship of amyloid markers to development of the earliest cognitive changes.