- Email: [email protected]
The relationship of cognition, cognitive reserve, and in vivo tau and amyloid burden
Podium Presentations: Monday, July 20, 2015
and non-carriers. We also sought to determine the extent to which ε4 carriage moderated EM decline in prodromal AD over the same interval. Methods: CN older adults (n¼333) and adults with MCI (n¼56) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Ab neuroimaging and ε4 genotyping. EM was assessed at baseline, 18-, 36-, 54- and 72-month followups. Ab PET neuroimaging was used to classify participants as Ab- or Ab+. Results: Relative to Ab-ε4- CNs, both Ab+ε4+ CNs and Ab+ε4- CNs showed significantly faster rates decline on EM over 72-months; however, Ab+ε4+ CNs showed significantly faster decline than Ab+ε4- CNs (Figure 1). Relative to Ab-ε4- CNs, both Ab+ε4- MCIs and Ab+ε4+ MCIs showed significantly faster rates of EM decline of a large magnitude over 72-months. There were no differences in rates of EM change between Ab-ε4- CNs and Ab-ε4+ CNs. Similarly, there were no differences in rates of EM change between Ab-ε4- CNs and Ab-ε4- MCIs (Figure 1). Conclusions: The results show for the first time that in CN older adults, Ab+ is associated with EM decline in ε4 non-carriers; however, the rate of this decline is much slower than that for ε4 carriers. Once individuals’ EM impairment is sufficient to meet clinical criteria for MCI, Ab related EM decline is unaffected by ε4 carriage. Thus, Ab and ε4 carriage act synergistically act to moderate the development of AD.
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left temporal lobe with intercept (baseline) and change (3 occasions) in Word List Recall and in Memory Functioning Questionnaire – Frequency of Forgetting. Higher connectivity in edges associated with DMN left temporal lobe at first occasion was associated both with level (intercept) and with decline (slope) in Word List Recall over 3 occasions. Higher connectivity in left temporal lobe edges at first occasion was also associated with subjects who reported increased (slope) frequency of forgetting over 3 occasions. Conclusions: Higher connectivity in DMN edges involving the left temporal lobe may be associated with longitudinal decline in memory recall and in longitudinal increase in frequency of forgetting. Higher connectivity in resting state may represent failure to deactivate or compensation. O2-02-03
THE RELATIONSHIP OF COGNITION, COGNITIVE RESERVE, AND IN VIVO TAU AND AMYLOID BURDEN
Dorene M. Rentz1,2,3, Elizabeth C. Mormino1, Rebecca Amariglio2,3, Kathryn V. Papp2,4, Reisa A. Sperling2,3,5, Keith A. Johnson2,6,7, 1 Massachusetts General Hospital, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Brigham and Women’s Hospital, Boston, MA, USA; 4Brigham and Women’s Hosptial, Boston, MA, USA; 5Massachusetts General Hospital and the Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA; 6Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 7Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Contact e-mail: [email protected] Background: The relationship between Alzheimer Disease (AD) bio-
Figure. *** O2-02-02
ASSOCIATION OF DEFAULT MODE CONNECTIVITY WITH MEMORY DECLINE AND SELF REPORT OF FREQUENCY OF FORGETTING
Sherry L. Willis, K. Warner Schaie, Paul Robinson, University of Washington, Seattle, WA, USA. Contact e-mail: [email protected] Background: Decline in memory recall is hallmark of progression to mild cognitive impairment (MCI) and possibly to Alzheimer’s Disease. While decreased connectivity in DMN occurs in AD, progression to MCI may be marked by early increase in activation/ connectivity. Methods: DMN fcMRI assessed at 2 occasions, over 2-years for 120 at risk older adults (mean age 70). Resting state fMRI conducted and processed through FSL melodic utility to decompose the data into group-level independent components and identify Default Mode Network (DMN). Cluster peaks from the DMN served as centers for 10mm radius R0Is. Mean time course from each R0I was correlated with every other R0I within subject to produce subject-specific correlation matrix. Neuropsychological assessment conducted at 3 occasions and scores derived on Word List Recall measure and Memory Functioning Questionnaire. Results: Word List Recall was correlated with DMN edges involving left temporal lobe (PCC-LTL; LPL-LTL; RPL-LTL). Growth curve analyses examined association of edges involving
markers and cognitive reserve (CR) on neuropsychological performance (NP) has important implications for understanding treatment effects in AD clinical trials. In this study we sought to determine whether NP is associated with Tau deposition using T807 Positron Emission Tomography (T807 Tau PET); Amyloid Beta (Ab) deposition using Pittsburgh Compound B (PiB PET) and whether CR modifies this relationship across a sample of cognitively normal elderly (CN), and patients with mild cognitive impairment (MCI) and AD dementia. Methods: A total of 106 subjects (CN¼95, MCI¼9, mild AD¼2), (mean age¼74.068.0; mean MMSE¼28.861.8) underwent NP testing, PiB PET and T807 Tau PET. CR was assessed with AMNART IQ. Using Multiple Linear Regression, we related a summary score of 11 NP tests (SUMCOG) to T807 Tau deposition in the inferior temporal lobe (IFT- Log transformed) and to PiB PETAb in an aggregate of AD cortical regions. In separate models predicting SUMCOG, we examined both the CR x T807 interaction and the CR x PIB interactions (controlling for age and sex). Results: In separate models, both greater T807 Tau (b¼-12.8, p <0.0001) and Ab (b¼-2.0, p<0.001) predicted lower SUMCOG. When T807 Tau and Ab were together in the model, T807 Tau remained significant (b¼-11.3, p<0.0001) but the effect of Ab diminished to trend level (b¼-0.6, p¼0.060). CR modified the relationship of T807 Tau and SUMCOG (b¼-0.5, p¼0.002) but not Ab and SUMCOG (b-0.0, p¼0.984). Conclusions: Higher Tau and Ab were both associated with lower NP, however, higher Tau had a more proximal effect on poorer cognition than Ab burden. These findings support the hypothetical AD model that Ab may have an earlier but weaker effect on cognition whereas elevation in inferior temporal Tau occurs more concurrently with cognitive decline. CR modified the association between NP and T807 Tau but not between NP and Ab burden. This finding suggests that CR may be protective against Tau-related cognitive impairment because of its proximal relationship to cognition. These findings may have important implications for AD clinical trials.
and non-carriers. We also sought to determine the extent to which ε4 carriage moderated EM decline in prodromal AD over the same interval. Methods: CN older adults (n¼333) and adults with MCI (n¼56) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Ab neuroimaging and ε4 genotyping. EM was assessed at baseline, 18-, 36-, 54- and 72-month followups. Ab PET neuroimaging was used to classify participants as Ab- or Ab+. Results: Relative to Ab-ε4- CNs, both Ab+ε4+ CNs and Ab+ε4- CNs showed significantly faster rates decline on EM over 72-months; however, Ab+ε4+ CNs showed significantly faster decline than Ab+ε4- CNs (Figure 1). Relative to Ab-ε4- CNs, both Ab+ε4- MCIs and Ab+ε4+ MCIs showed significantly faster rates of EM decline of a large magnitude over 72-months. There were no differences in rates of EM change between Ab-ε4- CNs and Ab-ε4+ CNs. Similarly, there were no differences in rates of EM change between Ab-ε4- CNs and Ab-ε4- MCIs (Figure 1). Conclusions: The results show for the first time that in CN older adults, Ab+ is associated with EM decline in ε4 non-carriers; however, the rate of this decline is much slower than that for ε4 carriers. Once individuals’ EM impairment is sufficient to meet clinical criteria for MCI, Ab related EM decline is unaffected by ε4 carriage. Thus, Ab and ε4 carriage act synergistically act to moderate the development of AD.
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left temporal lobe with intercept (baseline) and change (3 occasions) in Word List Recall and in Memory Functioning Questionnaire – Frequency of Forgetting. Higher connectivity in edges associated with DMN left temporal lobe at first occasion was associated both with level (intercept) and with decline (slope) in Word List Recall over 3 occasions. Higher connectivity in left temporal lobe edges at first occasion was also associated with subjects who reported increased (slope) frequency of forgetting over 3 occasions. Conclusions: Higher connectivity in DMN edges involving the left temporal lobe may be associated with longitudinal decline in memory recall and in longitudinal increase in frequency of forgetting. Higher connectivity in resting state may represent failure to deactivate or compensation. O2-02-03
THE RELATIONSHIP OF COGNITION, COGNITIVE RESERVE, AND IN VIVO TAU AND AMYLOID BURDEN
Dorene M. Rentz1,2,3, Elizabeth C. Mormino1, Rebecca Amariglio2,3, Kathryn V. Papp2,4, Reisa A. Sperling2,3,5, Keith A. Johnson2,6,7, 1 Massachusetts General Hospital, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Brigham and Women’s Hospital, Boston, MA, USA; 4Brigham and Women’s Hosptial, Boston, MA, USA; 5Massachusetts General Hospital and the Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA; 6Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 7Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Contact e-mail: [email protected] Background: The relationship between Alzheimer Disease (AD) bio-
Figure. *** O2-02-02
ASSOCIATION OF DEFAULT MODE CONNECTIVITY WITH MEMORY DECLINE AND SELF REPORT OF FREQUENCY OF FORGETTING
Sherry L. Willis, K. Warner Schaie, Paul Robinson, University of Washington, Seattle, WA, USA. Contact e-mail: [email protected] Background: Decline in memory recall is hallmark of progression to mild cognitive impairment (MCI) and possibly to Alzheimer’s Disease. While decreased connectivity in DMN occurs in AD, progression to MCI may be marked by early increase in activation/ connectivity. Methods: DMN fcMRI assessed at 2 occasions, over 2-years for 120 at risk older adults (mean age 70). Resting state fMRI conducted and processed through FSL melodic utility to decompose the data into group-level independent components and identify Default Mode Network (DMN). Cluster peaks from the DMN served as centers for 10mm radius R0Is. Mean time course from each R0I was correlated with every other R0I within subject to produce subject-specific correlation matrix. Neuropsychological assessment conducted at 3 occasions and scores derived on Word List Recall measure and Memory Functioning Questionnaire. Results: Word List Recall was correlated with DMN edges involving left temporal lobe (PCC-LTL; LPL-LTL; RPL-LTL). Growth curve analyses examined association of edges involving
markers and cognitive reserve (CR) on neuropsychological performance (NP) has important implications for understanding treatment effects in AD clinical trials. In this study we sought to determine whether NP is associated with Tau deposition using T807 Positron Emission Tomography (T807 Tau PET); Amyloid Beta (Ab) deposition using Pittsburgh Compound B (PiB PET) and whether CR modifies this relationship across a sample of cognitively normal elderly (CN), and patients with mild cognitive impairment (MCI) and AD dementia. Methods: A total of 106 subjects (CN¼95, MCI¼9, mild AD¼2), (mean age¼74.068.0; mean MMSE¼28.861.8) underwent NP testing, PiB PET and T807 Tau PET. CR was assessed with AMNART IQ. Using Multiple Linear Regression, we related a summary score of 11 NP tests (SUMCOG) to T807 Tau deposition in the inferior temporal lobe (IFT- Log transformed) and to PiB PETAb in an aggregate of AD cortical regions. In separate models predicting SUMCOG, we examined both the CR x T807 interaction and the CR x PIB interactions (controlling for age and sex). Results: In separate models, both greater T807 Tau (b¼-12.8, p <0.0001) and Ab (b¼-2.0, p<0.001) predicted lower SUMCOG. When T807 Tau and Ab were together in the model, T807 Tau remained significant (b¼-11.3, p<0.0001) but the effect of Ab diminished to trend level (b¼-0.6, p¼0.060). CR modified the relationship of T807 Tau and SUMCOG (b¼-0.5, p¼0.002) but not Ab and SUMCOG (b-0.0, p¼0.984). Conclusions: Higher Tau and Ab were both associated with lower NP, however, higher Tau had a more proximal effect on poorer cognition than Ab burden. These findings support the hypothetical AD model that Ab may have an earlier but weaker effect on cognition whereas elevation in inferior temporal Tau occurs more concurrently with cognitive decline. CR modified the association between NP and T807 Tau but not between NP and Ab burden. This finding suggests that CR may be protective against Tau-related cognitive impairment because of its proximal relationship to cognition. These findings may have important implications for AD clinical trials.