Fiona Lamb

Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study

Background We assessed the clinical utility of β-amyloid (Aβ) imaging with 18F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimers disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time. Methods 45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <−1.5. Results At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB−, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB− developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB− had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB−. Conclusions 18F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline. Trial registration number NCT01138111.

18F-florbetaben Aβ imaging in mild cognitive impairment

Introduction18F-florbetaben and positron emission tomography were used to examine the relationships between β-amyloid (Aβ) deposition, cognition, hippocampal volume, and white matter hyperintensities in mild cognitive impairment (MCI).MethodsForty-five MCI participants were evaluated. A neocortical standardized uptake value ratio threshold ≥ 1.45 was used to discriminate high from low Aβ burden. Correlations were adjusted for age, gender and years of education.ResultsHigh Aβ burden was found in 53% of MCI. Regression analyses showed standardized uptake value ratio (r = -0.51, P = 0.0015) and hippocampal volume (r = 0.60, P = 0.024) both contributing to episodic memory impairment in independent fashion. White matter hyperintensities correlated with nonmemory cognition, and this correlation was particularly associated with Aβ burden.ConclusionHigher Aβ deposition in MCI is associated with more severe memory impairment and is contributing to early amnestic symptoms independent of hippocampal atrophy.

Prediction of Amyloid-β Pathology in Amnestic Mild Cognitive Impairment with Neuropsychological Tests

Assessment of disease biomarkers, particularly the in vivo assessment of amyloid-β (Aβ) burden with positron emission tomography (PET), is gradually becoming central to the diagnosis of mild cognitive impairment (MCI) due to Alzheimers disease (AD). However, the incorporation of biomarker evidence to the diagnostic process is currently restricted mainly to research settings. The identification of memory measures that are associated with Aβ is of clinical relevance as this may enhance the confidence in making a diagnosis of MCI due to AD in clinical settings. Forty one persons with amnestic MCI underwent Aβ imaging with (18)F-Florbetaben PET, magnetic resonance imaging, and a comprehensive neuropsychological assessment. All measures of episodic memory were significantly correlated with Aβ burden, but regression analyses revealed a strong and selective association between story recall and Aβ over and beyond the effects of age, education, global cognition, hippocampal volume, or other memory tests. Analyses of sensitivity and specificity of memory measures to detect high versus low Aβ scans suggested that word-list recall performed better when high sensitivity was preferred, whereas story recall performed better when high specificity was preferred. In conclusion, a measure of story recall may increase the confidence in making a diagnosis of MCI due to AD in clinical settings.

Conversion from mild cognitive impairment to Alzheimer's disease over 12 months: Predictive value of Aβ imaging with 18F-Florbetaben

in mild cognitive impairment patients subsequently diagnosed with probable Alzheimer’s disease (Olichney et al., 2008), and a feedback-locked P300 which we believe is reflective of participants’ confidence in their category learning. Younger adults showed similar patterns for the late positive complex and P300 event-related potentials as in our original study (Morrison, Reber, and Paller, 2009). Because of the previously described differences in accuracy between the rule and no-rule subgroups, we examined event-related potentials separately in these two subgroups. The rule subgroup showed a larger late positive complex for correct than incorrect trials, similar in magnitude to that observed for younger adults. The no-rule subgroup showed no late positive complex differences between correct and incorrect trials. The rule subgroup also showed a feedback P300 difference for correct/incorrect trials, but it was smaller than that in younger adults, suggesting decreased rule-learning confidence (despite similar accuracy across groups). The no-rule subgroup showed event-related potentials characteristic of chance performance, with no differences between correct and incorrect trials in the feedback-locked P300, paralleling the lack of an effect on the stimulus-locked late positive complex.There were no significant differences in the control task between younger and older adults. Rule and norule older adults also performed similarly showing performance approximately equal to the asymptotic categorization performance for the rule-subgroup during the primary task. This suggests that no-rule subgroup categorization performance was likely reflecting deficits in long-term memory or executive functions. Conclusions: Preliminary results in this study showed that a simple rule-based category-learning task elicited differential performance and event-related potential findings as a function of age. We focused on findings from a group of older adults known to have long-term memory within the normal range on standard neuropsychological tests. Yet, some members of this group were successful in learning to categorize stimuli and some were not. We thus identified two distinct subgroups of healthy older individuals, one subgroup with category learning similar to college students and the other with dramatic deficits. Event-related potentialss recorded during categorization confirmed this stratification. Specifically a stimulus-locked late positive complex believed to index long-term memory was preserved in older adults who learned to categorize, but not in the others. Secondly a feedback-locked P300 believed to reflect the degree to which the participant is confident in their category learning showed a graded decrement. P300 differences for feedback on correct versus incorrect trials were greatest in amplitude in younger adults, intermediate in rulelearning older adults, and smallest in those older adults who failed to learn to categorize. The current study suggests that rule-based category learning, a task utilizing long-termmemory and executive functions, may be an effective means for identifying individuals at increased risk for mild cognitive impairment and probable Alzheimer’s disease. Event-related potentials recorded during this task may provide a more sensitive measure of changes in cognition compared to simple neuropsychological tests by measuring neural function even when participants perform well, thus providing an objective measure of confidence in learning. Future work will be directed at testing patients with mild cognitive impairment and Alzheimer’s disease using this paradigm.

EVALUATION OF [F-18]-PI-2620, A SECOND-GENERATION SELECTIVE TAU TRACER, FOR THE ASSESSMENT OF ALZHEIMER’S AND NON-ALZHEIMER’S TAUOPATHIES

III) in subjects with PD. In a cross-sectional analysis, we detected no effect of the monoamine oxidase B (MAO-B) inhibitor rasagiline on Flortaucipir binding. Conclusions: DLB patients show increased parietal Flortaucipir uptake. An increase in parietal tau is associated with executive impairment in patients with synocleinopathies. Decreased retention in the substantia nigra is associated with higher scores on the UPDRS motor scale. Further, our data indicate that Flortaucipir does not significantly bind to MAO-B in vivo. The retention levels of Flortaucipir in synucleinopathies are generally low compared to the retention seen in Alzheimer’s Disease, and the clinical usefulness of Flortaucipir in the differential diagnosis of PD/DLB is questionable.

TAU, Aβ-AMYLOID, BRAIN STRUCTURE AND COGNITIVE FUNCTION FOLLOWING SERVICE-RELATED TRAUMATIC BRAIN INJURY IN AUSTRALIAN VIETNAM WAR VETERANS

IC-P-091 TAU, Ab-AMYLOID, BRAIN STRUCTURE AND COGNITIVE FUNCTION FOLLOWING SERVICE-RELATED TRAUMATIC BRAIN INJURY IN AUSTRALIAN VIETNAM WARVETERANS Tia L. Cummins, Ying Xia, Alby Elias, Fiona Lamb, Kerstin Pannek, Vincent Dore, Pierrick Bourgeat, Robert Williams, Olivier Salvado, Jurgen Fripp, Jennie Ponsford, Victor L. Villemagne, Mal Hopwood, Christopher Rowe, Austin Health, Melbourne, Australia; The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; Commonwealth Scientific and Industrial Research Organisation, Brisbane, Australia; Commonwealth Scientific and Industrial Research Organisation, Brisbane, Australia; Commonwealth Scientific and Industrial Research Organisation, Brisbane, Australia; Monash University, Melbourne, Australia; University of Melbourne, Melbourne, Australia. Contact e-mail: tia.cummins@florey.edu.au

PTSD AND RISK OF ALZHEIMER’S DISEASE IN AUSTRALIAN VIETNAM VETERANS: AMYLOID AND TAU PET FINDINGS FROM AIBL-VETS

ambiguous (“Hard”) and unambiguous (“Easy”) words for animacy. Modulatory capacity was measured by contrasting hard vs. easy in functional activation. Age, amyloid and crystallized ability were entered in a multiple regression model for each of the 8 brain regions in the frontoparietal cognitive control network to assess whether amyloid and crystallized knowledge accounted for variance in modulation beyond age. Results:We first replicated our previous findings that older adults had decreased modulatory capacity in the frontoparietal network. After controlling for age, amyloid accumulation was related to declined modulatory capacity in parietal and right prefrontal but not left prefrontal cortex, and such depletive effects were found in middle-aged (40-60 years) but not older (60-69 years) adults. After controlling for age and continuous accumulation of amyloid, better crystallized knowledge predicted higher modulation in the frontoparietal network. Because we were particularly interested in whether the facilitating role of crystallized knowledge in modulatory capacity was related to amyloid positivity status, in a second analysis, we conducted multiple regressions with age and crystallized knowledge predicting brain modulation for amyloid negative and positive individuals, respectively.We found that better crystallized knowledge predicted higher modulatory capacity in prefrontal regions and left angular gyrus for amyloid negative individuals but only mildly (p1⁄4 0.057) in medial superior frontal gyrus for amyloid positive individuals. Conclusions: Our findings suggested that brain modulatory capability is impaired with age and amyloid. Crystallized knowledge protects modulatory capacity, which seems to have stronger effects for amyloid negative individuals, compared to amyloid positive individuals.

β-AMYLOID AND TAU IMAGING IN OBSTRUCTIVE SLEEP APNOEA: AUSTRALIAN IMAGING BIOMARKERS AND LIFESTYLE-VETERANS STUDY (AIBL-VETS)

Age -0.023 6 0.00478 £0.0001 -0.01 6 0.00413 0.0132 0.006 6 0.00296 0.043 Women 0.16909 6 0.0349 £0.0002 0.1122 6 0.03 0.0002 -0.02569 6 0.02160 0.2353 Level of education 0.0007 6 0.008 0.9274 -0.01256 6 0.00699 0.0731 -0.00131 6 0.00499 0.7931 ApoE4 status -0.0811 6 0.0417 0.0527 -0.00742 6 0.03596 0.8367 0.12261 6 0.02582 <0.0001 WMH volume -0.00172 6 0.00136 0.2 0.00106 6 0.00117 0.3645 0.00322 6 0.0008411 0.0002 Podium Presentations: Monday, July 17, 2017 P568

IN VIVO ASSESSMENT OF MARKERS OF ALZHEIMER’S DISEASE PATHOLOGY IN VIETNAM WAR VETERANS WITH CHRONIC POST-TRAUMATIC STRESS DISORDER

Geriatriezentrum Berlin, Berlin, Germany; Jung Diagnostics GmbH, Hamburg, Germany; 4 University Hospital Magdeburg, Magdeburg, Germany; 5 Vivantes Ida Wolff Krankenhaus, Berlin, Germany; 6 Sorbonne Universites, Universite Pierre et Marie Curie, Paris, France; Hopital de la Pitie-Salpetriere, Paris, France; AXA Research Fund & UPMC Chair, Paris, France; 9 Inserm U1127, Institut du Cerveau et de la Moelle Epiniere (ICM), Paris, France. Contact e-mail: catharina.lange@charite.de