- Email: [email protected]
SUBJECTIVE MEMORY COMPLAINTS ARE ASSOCIATED WITH BRAIN ACTIVATION SUPPORTING SUCCESSFUL MEMORY ENCODING
Poster Presentations: Saturday, July 23, 2016
Figure 1. Larger WMH volume is associated with a lower score on MFQ frequency of forgetting, indicating more severe memory complaints. Table 1 Subject Characteristics
Age (mean years, range) Sex (m/f) Systolic blood pressure Diastolic blood pressure IQ Geriatric Depression Scale Beck Depression Inventory Neuroticism (BFI) Conscientiousness (BFI) MFQ Frequency of forgetting
SCI (n¼25)
Controls (n¼42)
P¼value
68 (45-84) 7/18 138 81 101.8 5.4 6.9 19.4 34.2 143.9
68 (50-85) 17/25 140 81 104.9 3.1 4.4 17.1 36.5 175.9
0.961 0.303 0.596 0.773 0.420 0.0.26 0.090 0.110 0.107 0.000
Table 2 Cognitive functioning in the SCI and control group
MMSE WMS IV AMI WMS IV VMI WMS IV VWMI WMS IV IMI WMS IV DMI RAVLT total Verbal fluency Digital symbol Stroop 2 Stroop 3 TMT A TMT B
SCI (n¼25)
Controls (n¼42)
p-value
28.7 82.1 166.7 31.4 148.4 100.4 43.2 39.3 46.8 69.6 127.8 43.3 101.7
29 86.4 179.2 35.5 156.4 108.1 43.6 41.7 50.2 67.9 118.9 42.9 98.8
0.428 0.376 0.133 0.070 0.217 0.186 0.857 0.227 0.391 0.668 0.941 0.941 0.874
P107
Background: Subjective cognitive impairment (SCI) is associated with future cognitive decline. In SCI patients, Alzheimer’s disease (AD) - associated changes may already occur before cognitive decline becomes evident. Small vessel disease (SVD) is also related to cognitive decline. However little is known about SVD MRI markers in SCI. We investigate which MRI markers of AD and SVD are associated with severity of SCI. Methods: 67 healthy older adults (25 SCI and 42 controls) were included in the study (table 1). Severity of subjective memory complaints was assessed using the frequency of forgetting subscale of the Memory Functioning Questionnaire (Gilewski et al., Psychol Aging, 1990). All participants underwent 3T MRI with T1-w, T2-w, T2*-w and FLAIR scans. AD MRI markers were: whole brain gray and white matter volume and hippocampal volume. SVD MRI markers were: white matter hyperintensity (WMH) volume and number of microbleeds. To assess objective cognitive function we administered a neuropsychological test battery (table 2) and depression and personality questionnaires. Results: We found lower scores, i.e. more complaints, on frequency of forgetting in SCI than controls (table 1). We found no significant differences in cognitive function between groups (table 2). Of the AD and SVD MRI markers tested, WMH volume was significantly associated with frequency of forgetting; r¼-0.281, p¼0.027, adjusted for age, sex, nation and depression, indicating that increased severity of WMH volume is related to more severe memory complaints (figure 1). Other MRI markers were not associated with frequency of forgetting. Examination of the association between MRI markers and SCI participants versus controls (per MRI marker and for all MRI markers together), showed a trend level group effect on WMH volume (respectively p¼0.079 and p¼0.057 (table 3)) adjusted for age, sex, nation and depression, suggesting larger WMH volumes in SCI participants. Other MRI markers did not show any group differences. Conclusions: Our results indicate that severity of memory complaints is related to greater WMHs in healthy older adults, independent of objective cognitive function and depressive symptoms. WMHs are a prominent marker for SVD, which appears to be an important factor contributing to SCI and possibly future cognitive decline.
IC-P-145
SUBJECTIVE MEMORY COMPLAINTS ARE ASSOCIATED WITH BRAIN ACTIVATION SUPPORTING SUCCESSFUL MEMORY ENCODING
Jessica M. Hayes, Lingfei Tang, Noa Ofen, Jessica S. Damoiseaux, Wayne State University, Detroit, MI, USA. Contact e-mail: jessica.hayes2@wayne. edu Background: Subjective memory complaints (SMC), the perceived
decline in cognitive abilities in the absence of deficits on clinical
Table 3 MRI markers in the SCI and control group MRI marker AD Markers Vascular markers
3
GM volume (cm ) WM volume (cm3) Hippo (cm3) WMHS (cm3) Microbleeds
SCI (mean (SD)) (n¼25)
Controls (mean (SD)) (n¼42)
p-value per marker
p-value all in one model
698.7 (77.4) 794.9 (70.7) 6.8 (1.2) 16.3 (21.3) 0.16 (0.4)
713.4 (87.9) 781.6 (74.4) 7.0 (0.9) 739 (4.6) 0.06 (0.2)
0.505 0.754 0.222 0.079 0.234
0.165 0.416 0.609 0.057 0.485
p- values of logistic regression analysis.
P108
Poster Presentations: Saturday, July 23, 2016
Figure 1. Contrast map of high-confidence hits versus misses showing activation during successful memory formation that is associated with frequency of forgetting.
Figure 2. Results depicting the correlation between activation in the precuneus and PCC during successful memory formation and frequency of forgetting scores. Lower scores on frequency of forgetting indicate greater complaints. For visualization purposes the order of values on x-axis has been reversed so that from left to right scores indicate an increasing number of complaints.
ory effects (SME) have been found in the hippocampus among aMCI patients (Trivedi et al., 2008). Here we investigate the relationship between SME and frequency of memory complaints. Methods: 65 healthy older adults (mean age¼67.96, SD¼8.67, range 50-85) with concerning memory complaints (n¼23) and without (n¼42), were recruited and tested in Detroit and Leiden. Participants completed the frequency of forgetting (FoF) subscale of the Memory Functioning Questionnaire (Gilewski, Zelinski, Schaie, 1990), performed a memory encoding task in a 3T scanner, and a subsequent retrieval task post-scan. SME were calculated as the difference between activation during encoding of later remembered items (high-confidence hits) versus later forgotten items (misses). Whole-brain analyses with a General Linear Model, as implemented in FSL (Jenkinson et al., 2012) was used to identify regions in which SME correlated with FoF, controlling for age and gender. The correlation of task performance with FoF and with the magnitude of the SME was further explored. Results: The magnitude of the SME in the posterior cingulate and precuneus was positively correlated with FoF (Figure 1). Participants with more frequent memory complaints had more negative SME in this region (r¼.345, p<.01) (Figure 2). SME were also correlated with better task performance across the entire sample (r¼-.315, p<.05) (Figure 3). Both effects remained significant in just the SMC group (r¼.450, p<.05; and r¼-.491, p<.05 respectively). FoF was not correlated with task performance. Conclusions: The relation between SME in these areas and individuals’ level of frequent memory complaints may reflect a need for increased attention and effort among individuals with SMC to perform at normal levels. A compensatory mechanism could explain the disparity between levels of subjective and objective memory functioning in SMC. IC-P-146
MCI TRIAL ENRICHMENT USING MRI HIPPOCAMPUS TEXTURE
Lauge Sørensen1,2, Christian Igel1, Mads Nielsen1,2, 1University of Copenhagen, Copenhagen, Denmark; 2Biomediq A/S, Copenhagen, Denmark. Contact e-mail: [email protected] Background: Magnetic resonance imaging (MRI) hippocampal vol-
Figure 3. Results depicting the correlation between activation in the precuneus and PCC during successful memory formation and task performance.
assessments, may precede amnestic mild cognitive impairment (aMCI) in the Alzheimer’s disease timeline (Reisberg et al., 2008). Individuals with SMC show increased activation in the prefrontal cortex during memory encoding (Rodda et al., 2009), however, it is not clear whether the increase is specific for later remembered versus later forgotten items. Greater subsequent mem-
ume has been qualified by the European Medicines Agency (EMA) as an enrichment biomarker for mild cognitive impairment (MCI) trials [1]. We tested the potential of adding MRI hippocampal texture [2] for further enrichment of MCI trials. Methods: The MCI subjects from the “complete annual year 2 visit” 1.5T standardized Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset [3] that had an associated cerebrospinal fluid (CSF) measurement available from the Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia [4] were identified (127 subjects, age 74.567.4, 30.7% female, mini-mental state examination [MMSE] 26.961.8, Alzheimer’s Disease Assessment Scale-cognitive subscale [ADAS-Cog] 18.666.2).Two T1weighted MRI biomarkers were computed: hippocampal volume divided by intra-cranial volume (cross-sectional FreeSurfer v.5.1.0, default parameters), and hippocampal texture (in house software). In addition, we used log(total tau / Ab 1 to 42 peptide) as CSF biomarker. Biomarkers were combined using linear regression with change in cognitive score over two years as dependent variable. Costs were computed based on sample size estimates and using the same price for MRI and CSF assessment. Results: Effect size and corresponding cost were monitored as a function of number of subjects selected for both MMSE and ADAS-cog (see Figure). Texture generally demonstrated larger effect size while at the same time
Figure 1. Larger WMH volume is associated with a lower score on MFQ frequency of forgetting, indicating more severe memory complaints. Table 1 Subject Characteristics
Age (mean years, range) Sex (m/f) Systolic blood pressure Diastolic blood pressure IQ Geriatric Depression Scale Beck Depression Inventory Neuroticism (BFI) Conscientiousness (BFI) MFQ Frequency of forgetting
SCI (n¼25)
Controls (n¼42)
P¼value
68 (45-84) 7/18 138 81 101.8 5.4 6.9 19.4 34.2 143.9
68 (50-85) 17/25 140 81 104.9 3.1 4.4 17.1 36.5 175.9
0.961 0.303 0.596 0.773 0.420 0.0.26 0.090 0.110 0.107 0.000
Table 2 Cognitive functioning in the SCI and control group
MMSE WMS IV AMI WMS IV VMI WMS IV VWMI WMS IV IMI WMS IV DMI RAVLT total Verbal fluency Digital symbol Stroop 2 Stroop 3 TMT A TMT B
SCI (n¼25)
Controls (n¼42)
p-value
28.7 82.1 166.7 31.4 148.4 100.4 43.2 39.3 46.8 69.6 127.8 43.3 101.7
29 86.4 179.2 35.5 156.4 108.1 43.6 41.7 50.2 67.9 118.9 42.9 98.8
0.428 0.376 0.133 0.070 0.217 0.186 0.857 0.227 0.391 0.668 0.941 0.941 0.874
P107
Background: Subjective cognitive impairment (SCI) is associated with future cognitive decline. In SCI patients, Alzheimer’s disease (AD) - associated changes may already occur before cognitive decline becomes evident. Small vessel disease (SVD) is also related to cognitive decline. However little is known about SVD MRI markers in SCI. We investigate which MRI markers of AD and SVD are associated with severity of SCI. Methods: 67 healthy older adults (25 SCI and 42 controls) were included in the study (table 1). Severity of subjective memory complaints was assessed using the frequency of forgetting subscale of the Memory Functioning Questionnaire (Gilewski et al., Psychol Aging, 1990). All participants underwent 3T MRI with T1-w, T2-w, T2*-w and FLAIR scans. AD MRI markers were: whole brain gray and white matter volume and hippocampal volume. SVD MRI markers were: white matter hyperintensity (WMH) volume and number of microbleeds. To assess objective cognitive function we administered a neuropsychological test battery (table 2) and depression and personality questionnaires. Results: We found lower scores, i.e. more complaints, on frequency of forgetting in SCI than controls (table 1). We found no significant differences in cognitive function between groups (table 2). Of the AD and SVD MRI markers tested, WMH volume was significantly associated with frequency of forgetting; r¼-0.281, p¼0.027, adjusted for age, sex, nation and depression, indicating that increased severity of WMH volume is related to more severe memory complaints (figure 1). Other MRI markers were not associated with frequency of forgetting. Examination of the association between MRI markers and SCI participants versus controls (per MRI marker and for all MRI markers together), showed a trend level group effect on WMH volume (respectively p¼0.079 and p¼0.057 (table 3)) adjusted for age, sex, nation and depression, suggesting larger WMH volumes in SCI participants. Other MRI markers did not show any group differences. Conclusions: Our results indicate that severity of memory complaints is related to greater WMHs in healthy older adults, independent of objective cognitive function and depressive symptoms. WMHs are a prominent marker for SVD, which appears to be an important factor contributing to SCI and possibly future cognitive decline.
IC-P-145
SUBJECTIVE MEMORY COMPLAINTS ARE ASSOCIATED WITH BRAIN ACTIVATION SUPPORTING SUCCESSFUL MEMORY ENCODING
Jessica M. Hayes, Lingfei Tang, Noa Ofen, Jessica S. Damoiseaux, Wayne State University, Detroit, MI, USA. Contact e-mail: jessica.hayes2@wayne. edu Background: Subjective memory complaints (SMC), the perceived
decline in cognitive abilities in the absence of deficits on clinical
Table 3 MRI markers in the SCI and control group MRI marker AD Markers Vascular markers
3
GM volume (cm ) WM volume (cm3) Hippo (cm3) WMHS (cm3) Microbleeds
SCI (mean (SD)) (n¼25)
Controls (mean (SD)) (n¼42)
p-value per marker
p-value all in one model
698.7 (77.4) 794.9 (70.7) 6.8 (1.2) 16.3 (21.3) 0.16 (0.4)
713.4 (87.9) 781.6 (74.4) 7.0 (0.9) 739 (4.6) 0.06 (0.2)
0.505 0.754 0.222 0.079 0.234
0.165 0.416 0.609 0.057 0.485
p- values of logistic regression analysis.
P108
Poster Presentations: Saturday, July 23, 2016
Figure 1. Contrast map of high-confidence hits versus misses showing activation during successful memory formation that is associated with frequency of forgetting.
Figure 2. Results depicting the correlation between activation in the precuneus and PCC during successful memory formation and frequency of forgetting scores. Lower scores on frequency of forgetting indicate greater complaints. For visualization purposes the order of values on x-axis has been reversed so that from left to right scores indicate an increasing number of complaints.
ory effects (SME) have been found in the hippocampus among aMCI patients (Trivedi et al., 2008). Here we investigate the relationship between SME and frequency of memory complaints. Methods: 65 healthy older adults (mean age¼67.96, SD¼8.67, range 50-85) with concerning memory complaints (n¼23) and without (n¼42), were recruited and tested in Detroit and Leiden. Participants completed the frequency of forgetting (FoF) subscale of the Memory Functioning Questionnaire (Gilewski, Zelinski, Schaie, 1990), performed a memory encoding task in a 3T scanner, and a subsequent retrieval task post-scan. SME were calculated as the difference between activation during encoding of later remembered items (high-confidence hits) versus later forgotten items (misses). Whole-brain analyses with a General Linear Model, as implemented in FSL (Jenkinson et al., 2012) was used to identify regions in which SME correlated with FoF, controlling for age and gender. The correlation of task performance with FoF and with the magnitude of the SME was further explored. Results: The magnitude of the SME in the posterior cingulate and precuneus was positively correlated with FoF (Figure 1). Participants with more frequent memory complaints had more negative SME in this region (r¼.345, p<.01) (Figure 2). SME were also correlated with better task performance across the entire sample (r¼-.315, p<.05) (Figure 3). Both effects remained significant in just the SMC group (r¼.450, p<.05; and r¼-.491, p<.05 respectively). FoF was not correlated with task performance. Conclusions: The relation between SME in these areas and individuals’ level of frequent memory complaints may reflect a need for increased attention and effort among individuals with SMC to perform at normal levels. A compensatory mechanism could explain the disparity between levels of subjective and objective memory functioning in SMC. IC-P-146
MCI TRIAL ENRICHMENT USING MRI HIPPOCAMPUS TEXTURE
Lauge Sørensen1,2, Christian Igel1, Mads Nielsen1,2, 1University of Copenhagen, Copenhagen, Denmark; 2Biomediq A/S, Copenhagen, Denmark. Contact e-mail: [email protected] Background: Magnetic resonance imaging (MRI) hippocampal vol-
Figure 3. Results depicting the correlation between activation in the precuneus and PCC during successful memory formation and task performance.
assessments, may precede amnestic mild cognitive impairment (aMCI) in the Alzheimer’s disease timeline (Reisberg et al., 2008). Individuals with SMC show increased activation in the prefrontal cortex during memory encoding (Rodda et al., 2009), however, it is not clear whether the increase is specific for later remembered versus later forgotten items. Greater subsequent mem-
ume has been qualified by the European Medicines Agency (EMA) as an enrichment biomarker for mild cognitive impairment (MCI) trials [1]. We tested the potential of adding MRI hippocampal texture [2] for further enrichment of MCI trials. Methods: The MCI subjects from the “complete annual year 2 visit” 1.5T standardized Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset [3] that had an associated cerebrospinal fluid (CSF) measurement available from the Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia [4] were identified (127 subjects, age 74.567.4, 30.7% female, mini-mental state examination [MMSE] 26.961.8, Alzheimer’s Disease Assessment Scale-cognitive subscale [ADAS-Cog] 18.666.2).Two T1weighted MRI biomarkers were computed: hippocampal volume divided by intra-cranial volume (cross-sectional FreeSurfer v.5.1.0, default parameters), and hippocampal texture (in house software). In addition, we used log(total tau / Ab 1 to 42 peptide) as CSF biomarker. Biomarkers were combined using linear regression with change in cognitive score over two years as dependent variable. Costs were computed based on sample size estimates and using the same price for MRI and CSF assessment. Results: Effect size and corresponding cost were monitored as a function of number of subjects selected for both MMSE and ADAS-cog (see Figure). Texture generally demonstrated larger effect size while at the same time