- Email: [email protected]
NEUROPSYCHIATRIC SYMPTOMS AND ALZHEIMER DISEASE BIOMARKERS PREDICT DRIVING DECLINE
Poster Presentations: Wednesday, July 19, 2017
P1335
University in St. Louis School of Medicine, St. Louis, MO, USA; Knight Alzheimer Disease Center, St. Louis, MO, USA. Contact e-mail: [email protected] 8
Background: Changes in cognitive and neurobehavioral processes
Background: Subjective cognitive decline (SCD) is considered an early aspecific clinical marker for Alzheimer’s disease (AD). In this study, we wanted to search for a specific pattern of SCD in asymptomatic individuals at risk for AD. Methods: Cognitively normal older adults (N¼318) reporting SCD and their informants were enrolled in the INSIGHT-PreAD cohort. Subjects performed 6 questionnaires assessing different aspects of SCD. We examined the relationship between these SCD measures and AD neuroimaging markers (amyloid burden assessed by 18F-florbetapir (18F-AV-45 [AmyvidÔ, Avid Radiopharmaceuticals]) PET, hippocampal atrophy by structural magnetic resonance imaging and brain hypometabolism by FDG-PET). We introduced an index of cognitive awareness resorting to the subject-informant discrepancy in a questionnaire of SCD, and compared the participants with high versus low awareness of their cognitive functioning. Results: None of the SCD questionnaires was correlated with AD neuroimaging markers (all r<.206). Comparing subjects with a low (n¼19) and high (n¼86) level of awareness, there was no significant difference in terms of demography, neuropsychiatric symptoms, autonomy, quality of life, cognition and hippocampal volume. The mean amyloid standardized uptake value ratio was significantly higher for the “low awareness” group compared to the “high awareness” group (p¼.011). In addition, the proportion of amyloid positive subjects in the “low awareness” group was twice as large as in the “high awareness” group (47% vs 24%, p¼.045). Furthermore, the “low awareness” group showed glucose hypometabolism, particularly in all the brain regions affected by AD (posterior cingulate cortex, inferior parietal lobule, precuneus and inferior temporal gyrus). Conclusions: This study provided additional evidence that reporting SCD by itself is not a specific clinical marker of preclinical AD. Conversely, a low level of cognitive awareness (namely, when the subjects reported less difficulties than their informants) may represent a very early form of anosognosia and serve as a specific indicator of preclinical AD. This finding is of key importance as an enrichment factor in both clinical practice and research trials. P4-185
NEUROPSYCHIATRIC SYMPTOMS AND ALZHEIMER DISEASE BIOMARKERS PREDICT DRIVING DECLINE
Ganesh M. Babulal1, Sarah Holtz Stout1, Denise M. Head1, David M. Holtzman1,2,3,4,5,6,7, Anne M. Fagan1,4,6, John C. Morris1,5,6, Catherine M. Roe1,8, 1Washington University School of Medicine, St. Louis, MO, USA; 2Washington University School of Medicine, Saint Louis, MO, USA; 3Hope Center for Neurological Disorders, Saint Louis, MO, USA; 4Hope Center for Neurological Disorders, St. Louis, MO, USA; 5Washington University in St. Louis, St. Louis, MO, USA; 6Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA; 7Washington
begin in the long preclinical stage of Alzheimer disease (AD). In older adults, mood states and neuropsychiatric symptoms (NPS) predict progression to symptomatic AD. We examined whether mood states and NPS interact with cerebrospinal fluid (CSF) biomarkers (b-amyloid42 [Ab42], tau, phosphorylated tau181 [ptau181], tau/Ab42 and ptau181/Ab42) of underlying AD pathology to predict driving decline among cognitively normal older adults. Methods: Participants, 65 years of age or older, were enrolled from longitudinal studies at the Knight Alzheimer’s Disease Research Center at Washington University. Cox proportional hazards models (CPHM) evaluated whether CSF biomarkers, mood states (Profile of Mood States-Short Form [POMS-SF]; Geriatric Depression Scale [GDS]) and NPS (Neuropsychiatric Inventory Questionnaire) were associated with time to receiving a rating of marginal or fail on the driving test. Age, education and gender were adjusted in the models. Results: Data were available from 116 participants with ages ranging from 65.6 to 88.2 years. There were statistically significant interactions with CSF biomarkers and NPS. Cox proportional hazards models showed that interactions between NPI-Q and Ab42 (p¼0.012), tau/Ab42 (p¼0.033) and ptau181/Ab42 (p¼0.038) biomarkers were significant in predicting time to a rating of Marginal/Fail on the road test (see Figure 1). Participants with NPS and more abnormal levels of Ab42, CSF tau/ Ab42 and ptau181/Ab42 were much faster to receive a marginal/fail rating on the road test compared to participants with no NPS or nonabnormal biomarkers. Models examining mood states were not statistically significant. Conclusions: Neuropsychiatric symptoms interact with abnormal CSF biomarkers to impact driving performance among cognitively normal older adults. While preclinical AD alone predicted a faster time to receiving a marginal/fail rating, the presence of NPS increases these problems compared to those without preclinical AD or NPS. Changes in neurobehavioral and cognitive processes begin in preclinical AD and also impact complex activities like driving.
P1335
University in St. Louis School of Medicine, St. Louis, MO, USA; Knight Alzheimer Disease Center, St. Louis, MO, USA. Contact e-mail: [email protected] 8
Background: Changes in cognitive and neurobehavioral processes
Background: Subjective cognitive decline (SCD) is considered an early aspecific clinical marker for Alzheimer’s disease (AD). In this study, we wanted to search for a specific pattern of SCD in asymptomatic individuals at risk for AD. Methods: Cognitively normal older adults (N¼318) reporting SCD and their informants were enrolled in the INSIGHT-PreAD cohort. Subjects performed 6 questionnaires assessing different aspects of SCD. We examined the relationship between these SCD measures and AD neuroimaging markers (amyloid burden assessed by 18F-florbetapir (18F-AV-45 [AmyvidÔ, Avid Radiopharmaceuticals]) PET, hippocampal atrophy by structural magnetic resonance imaging and brain hypometabolism by FDG-PET). We introduced an index of cognitive awareness resorting to the subject-informant discrepancy in a questionnaire of SCD, and compared the participants with high versus low awareness of their cognitive functioning. Results: None of the SCD questionnaires was correlated with AD neuroimaging markers (all r<.206). Comparing subjects with a low (n¼19) and high (n¼86) level of awareness, there was no significant difference in terms of demography, neuropsychiatric symptoms, autonomy, quality of life, cognition and hippocampal volume. The mean amyloid standardized uptake value ratio was significantly higher for the “low awareness” group compared to the “high awareness” group (p¼.011). In addition, the proportion of amyloid positive subjects in the “low awareness” group was twice as large as in the “high awareness” group (47% vs 24%, p¼.045). Furthermore, the “low awareness” group showed glucose hypometabolism, particularly in all the brain regions affected by AD (posterior cingulate cortex, inferior parietal lobule, precuneus and inferior temporal gyrus). Conclusions: This study provided additional evidence that reporting SCD by itself is not a specific clinical marker of preclinical AD. Conversely, a low level of cognitive awareness (namely, when the subjects reported less difficulties than their informants) may represent a very early form of anosognosia and serve as a specific indicator of preclinical AD. This finding is of key importance as an enrichment factor in both clinical practice and research trials. P4-185
NEUROPSYCHIATRIC SYMPTOMS AND ALZHEIMER DISEASE BIOMARKERS PREDICT DRIVING DECLINE
Ganesh M. Babulal1, Sarah Holtz Stout1, Denise M. Head1, David M. Holtzman1,2,3,4,5,6,7, Anne M. Fagan1,4,6, John C. Morris1,5,6, Catherine M. Roe1,8, 1Washington University School of Medicine, St. Louis, MO, USA; 2Washington University School of Medicine, Saint Louis, MO, USA; 3Hope Center for Neurological Disorders, Saint Louis, MO, USA; 4Hope Center for Neurological Disorders, St. Louis, MO, USA; 5Washington University in St. Louis, St. Louis, MO, USA; 6Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA; 7Washington
begin in the long preclinical stage of Alzheimer disease (AD). In older adults, mood states and neuropsychiatric symptoms (NPS) predict progression to symptomatic AD. We examined whether mood states and NPS interact with cerebrospinal fluid (CSF) biomarkers (b-amyloid42 [Ab42], tau, phosphorylated tau181 [ptau181], tau/Ab42 and ptau181/Ab42) of underlying AD pathology to predict driving decline among cognitively normal older adults. Methods: Participants, 65 years of age or older, were enrolled from longitudinal studies at the Knight Alzheimer’s Disease Research Center at Washington University. Cox proportional hazards models (CPHM) evaluated whether CSF biomarkers, mood states (Profile of Mood States-Short Form [POMS-SF]; Geriatric Depression Scale [GDS]) and NPS (Neuropsychiatric Inventory Questionnaire) were associated with time to receiving a rating of marginal or fail on the driving test. Age, education and gender were adjusted in the models. Results: Data were available from 116 participants with ages ranging from 65.6 to 88.2 years. There were statistically significant interactions with CSF biomarkers and NPS. Cox proportional hazards models showed that interactions between NPI-Q and Ab42 (p¼0.012), tau/Ab42 (p¼0.033) and ptau181/Ab42 (p¼0.038) biomarkers were significant in predicting time to a rating of Marginal/Fail on the road test (see Figure 1). Participants with NPS and more abnormal levels of Ab42, CSF tau/ Ab42 and ptau181/Ab42 were much faster to receive a marginal/fail rating on the road test compared to participants with no NPS or nonabnormal biomarkers. Models examining mood states were not statistically significant. Conclusions: Neuropsychiatric symptoms interact with abnormal CSF biomarkers to impact driving performance among cognitively normal older adults. While preclinical AD alone predicted a faster time to receiving a marginal/fail rating, the presence of NPS increases these problems compared to those without preclinical AD or NPS. Changes in neurobehavioral and cognitive processes begin in preclinical AD and also impact complex activities like driving.