Compromised cerebral autoregulation in patients with mild cognitive impairment

Poster Presentations: P3 completed (median interval¼109 days) telephone interviews, featuring the same 7-item questionnaire and a 9-measure neuropsychological battery encompassing: general cognition (Telephone Interview for Cognitive Status); immediate and delayed word and paragraph (East Boston Memory Test) recall; category fluency; working memory (digit span-backwards); executive function (Oral Trail-Making Test-B [OTMT-B]). Informants completed self-administered, validated questionnaires (Structured Interview and Scoring Tool-MADRC-Informant Report). Results: Absolute agreement between self- and telephone-administered STIDA items ranged from 5894%. Several items were infrequently endorsed; thus, chance-corrected agreement was predictably low (kappa range¼0.05-0.41; weighted kappa for sum-of-items¼0.33). Participants were more likely to endorse memory complaints (e.g., remembering a list of items) in self-administered vs. telephone-interview formats (45% v. 31%, McNemar’s P¼0.04). Participants were more likely to endorse memory problems (e.g., overall change in memory ability) than informants (80% vs. 52%, McNemar’s P<0.001); however, informants appeared more likely to report “executive” symptoms (e.g., trouble following group conversations or a plot: 16% vs. 7%, McNemar’s P¼0.06). Regarding neuropsychological testing, STIDA responses were generally uncorrelated with performance. However, informant reports were significantly related to objective testing: e.g., mean difference in global z -score averaging all tests¼-0.37 units (P¼0.03) for "trouble following group conversions/plots "-yes/no; mean difference in OTMT-B¼11.1 seconds (P¼0.05) for "difficulty understanding/following instructions "-yes/no. Conclusions: Participants were more likely to endorse complaints when providing unobserved, written responses versus during interviews, which may have important implications for screening in healthy samples without selfidentified memory concerns. Participants were more likely to report memory concerns, and informants to report executive problems. Finally, informantreported problems were associated with significantly worse objective global cognitive and executive performance, indicating validity and value of informant reports in cognitive studies using remote assessment methods. P3-088

THE AD8 DEMENTIA SCREENING TEST DETECTS MILD COGNITIVE IMPAIRMENT

James Galvin1, Catherine Roe2, John Morris3, 1New York University, New York, New York, United States; 2Washington University School of Medicine, St Louis, Missouri, United States; 3Washington University, St. Louis, Missouri, United States. Background: Detection of mild cognitive impairment (MCI) and early-stage Alzheimer’s disease (AD) can be done either by comparing individual cognitive performance with normative values or assessing cognitive decline within an individual. The AD8 is a widely used, validated, 8-item dementia screening tool; endorsement of >2 questions suggests cognitive impairment. The AD8 may improve detection of MCI and early-stage dementia in clinical practice and enrollment into MCI clinical trials. Methods: 810 individuals (CDR 0, Controls¼528; CDR 0.5/MCI¼102; CDR 0.5/AD¼180) were evaluated at the Washington University Knight Alzheimer’s Disease Research Center. Participants underwent identical assessments including all items from the Uniform Data Set, Clinical Dementia Rating (CDR) and Sum Boxes (CDR-SB). The AD8 questions were embedded throughout the interview. Receiver operator characteristic curves assessed ability of the AD8 to discriminate between CDR 0, CDR 0.5/MCI and CDR 0.5/AD. Results: The sample’s mean age¼75 + 8y; education¼15 + 3y; 56% female. Informants largely were spouses (52%) or adult children (26%). Mean CDR-SB was higher in AD (2.5) vs. MCI (0.9, P<.001). In MCI, the most frequently endorsed CDR domains were Memory (93.2%), Judgment and Problem Solving (47.1%) and Home and Hobbies (21.6%); these domains were also most frequently endorsed in AD. Mean AD8 scores for CDR 0¼0.5, CDR 0.5/MCI¼2.9, and CDR 0.5/AD¼5.3. MCI informants most frequently endorsed problems with judgment (61%); repeats questions/statements/stories (56%); daily problems with memory (52%); and trouble operating tools/gadgets/ appliances (37%). The AD8 discriminated Controls from (1) any cognitive impairment (.946; 95% CI: .92-96); (2) CDR 0.5 MCI (.879; 95% CI: .84.92); and (3) CDR 0.5 AD (.985; 95%CI: .98-.99) using a cut-off score¼2. The AD8 also discriminated MCI from AD (.840; 95%CI: .79-.89) using

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a cut-off score¼5. Conclusions: The AD8 detected the very mildest forms of cognitive impairment due to AD: CDR 0.5/MCI and CDR 0.5/AD. Cutoff scores 2-5 suggest MCI and cut-off scores >5 suggest AD. Higher AD8 scores correlated with more impaired ratings in clinical, cognitive, functional and behavioral domains and MCI does indeed affect everyday functioning.Thus, if simple and efficient screening for MCI in applied settings is the goal the AD8 could be recommended on the basis of utility and brevity. P3-089

COMMUNITY LIFE WITHDRAWAL WITH MCI PROGRESSION

Jeffrey Kaye, Nora Matteck, Tamara Hayes, Daniel Austin, Hiroko Dodge, Oregon Health and Science University, Portland, Oregon, United States. Background: The development of MCI may be associated with decreased levels of activity or withdrawal from the world as cognitive decline progresses. This change may be difficult to detect by self-report methods. Unobtrusive home-based sensing technologies may allow the detection of subtle changes in activity indicative of MCI. Methods: Volunteers enrolled in the Intelligent Systems for Assessing Aging Change (ISAAC) cohort study were followed longitudinally in their homes outfitted with embedded motion and contact sensors to detect 24/7 activity patterns. Time out of the home was the primary outcome of interest. Sensor data was used to sum the total time (in hours) out of house per month per participant. This time was divided by the number of valid days with monitored data per month to get average hours out of home per day per subject-month. Data were analyzed using a mixed effect model with random intercept and time effects adjusted for age, gender, education, Cumulative Illness Rating Scale and Geriatric Depression Scale score at baseline. Results: Data from 148 participants (28 with MCI; 10 with amnestic MCI), mean age, 84.2 6 5.0 were assessed for a mean of 2.8 6 1.2 years. During the first month after enrollment, participants spent a mean of 4.5 6 3.7 hours/day out of their home; there was no difference in time out of house between MCI and cognitively normal participants during the post-baseline month. In cognitively intact participants there was no longitudinal change in time out of home. MCI participants had a significantly greater decline in time out of home over time compared to cognitively intact participants. During the last month of monitored data, cognitively intact participants left their home 3.8 hours/per day on average; MCI participants left their home 2.9 hrs/day. Conclusions: With the progression of MCI increasingly less time is spent outside the home. This suggests a progressive narrowing of interaction with the outside world. This phenomenon may form a novel measure that can be used to unobtrusively detect early activity changes indicative of evolving MCI. P3-090

COMPROMISED CEREBRAL AUTOREGULATION IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT

Jie Liu1, Estee Brunk1, Yong-Sheng Zhu1, Kyle Armstrong1, Kristin Martin-Cook2, Linda Hynanc3, Myron Weiner3, Ramon DiazArrastia2, Benjamin D Levine1, Rong Zhang1, 1Institute for Exercise and Environmental Medicine,Texas Health Presbyterian Hospital Dallas, Dallas, Texas, United States; 2Alzheimer’s Disease Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States; 3 Alzheimer’s Disease Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States. Background: Cardiovascular risk factors appear to influence the development of Alzheimer’s disease (AD). However, the underlying mechanisms by which cerebrovascular dysfunction in particular contributes to AD is unknown. We tested the hypothesis that static cerebral autoregulation (sCA) is compromised in patients with amnestic mild cognitive impairment (MCI), a transitional state between normal cognitive aging and AD. Methods: 26 MCI patients (12 males, 67 6 6 yr) and 18 age-and education-matched normal control subjects (6 males, 68 6 7 yr) underwent cerebral autoregulation study. Mean Arterial blood pressure (MAP) was decreased stepwise by intravenous infusion of sodium nitroprusside (SNP) and then increased by phenylephrine. Transcranial and color duplex Doppler were used to measure cerebral blood flow (CBF) velocity of the middle cerebral artery (MCA, V MCA) and volumetric blood flow of the internal carotid (ICA, F ICA) and

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Poster Presentations: P3

vertebral arteries (VA, F VA) in response to changes in MAP. End-tidal CO 2 (ETCO 2) was recorded simultaneously. Stepwise multiple linear regression analysis was used to examine the effects of MAP, ET CO 2, group (0 for control, 1 for MCI), age and gender (0 for female, 1 for male) on V MCA, F ICA, and F VA (, percentage changes to baseline). Results: The range of variations in MAP induced by drug infusion was 65w143 mm Hg associated with a concomitant change in ETCO2 (range: 22w48 mm Hg). The regression equations derived were: VMCA ¼ 0.170*MAP + 0.530* ETCO2 + 0.189*Group + 0.252*Age, R ¼ 0.719, P < 0.001; FICA ¼ 0.212* ETCO2, R ¼ 0.237, P < 0.01; FVA ¼ 0.221*MAP + 0.262* ETCO2 + 0.256*Group, R ¼ 0.475, P < 0.001. Significantly different CBF responses to MAP and ETCO2 between the MCI and control groups were observed in the MCA and VA, but not in the ICA. No gender differences were observed. Conclusions: Cerebral autoregulatory dysfunction was detected in patients with MCI, most prominently in the MCA and posterior cerebral territory (supplied mainly by the VA). These findings suggest that cerebrovascular dysfunction is detectable at the early stage of AD. A cause-effect relationship has yet to be established. P3-091

STATIC BALANCE IMPAIRMENTS UNDER DUALTASK CONDITIONS IN MCI

Julia Leach, Martina Mancini, Jeffrey Kaye, Fay Horak, Tamara Hayes, Oregon Heath & Science University, Portland, Oregon, United States. Background: Motor changes precede cognitive changes in MCI and may be predictive of the development of MCI and later transition to dementia. Furthermore, cognitively impaired older adults are at an increased risk of falls due to decreased motor function and compromised balance. Although there is increasing evidence that both dynamic and static balance is compromised in this population, the relationship between MCI and postural control remains poorly understood. Methods: Nine volunteers enrolled in the Intelligent Systems for Assessing Aging Change (ISAAC) cohort study were recruited for this pilot study (4 naMCI, 3 aMCI, 2 cognitively-intact agematched controls; mean age, 80.8 6 6.7). Subjects wore six wireless inertial sensors (mounted on the left wrist, right wrist, left ankle, right ankle, lumbar, and trunk) for balance testing; only the results from the lumbar sensor are reported here. The protocol included seven trials of standing in place. One balance trial had no secondary task; the remaining six trials included secondary tasks that tapped into a variety of cognitive domains (working memory, attention, short- and long-term memory and executive function). Data were analyzed with a two-way, fixed effects analysis of variance (ANOVA). Post-hoc between-group comparisons were done using Tukey’s HSD criterion. Results: Several measures of static balance were examined; jerk (the time derivative (rate of change) of acceleration) showed significant differences across subjects. Figure 1 shows the mean value of jerk across each group and test condition. There was a significant effect of MCI status (F 2,42 ¼4.77, P¼0.01). Cross-group comparisons showed that this was due to a difference between the aMCI and control groups; although there was

a difference between naMCI and aMCI groups this did not reach significance. There were no effects of dual-task condition (F 6,42 ¼0.70, P¼0.65). Conclusions: These preliminary results suggest that jerk and other objective measures of quiet stance may help differentiate early stages of cognitive decline. Cognitive loading during balance testing amplifies postural instability and may make measures of quiet stance more sensitive. Further research will help determine if these measures predict increased fall risk and allow for better differentiation of MCI from healthy subjects. P3-092

SUBJECTIVE COGNITIVE COMPLAINT AND COGNITIVE PERFORMANCE AMONG OLDER ADULTS

Katherine Gifford1, Aaron Der2, Raymond Romano2, Brett Martin2, Nicole Cantwell2, Neil Kowall2, Angela Jefferson1, 1Vanderbilt University, Nashville, Tennessee, United States; 2Boston University, Boston, Massachusetts, United States. Background: Cognitive complaint is necessary to diagnosis mild cognitive impairment (MCI), yet no consensus exists for assessing such complaints. Common methods for assessing complaints are compared to cognitive performances among older adults with normal cognition (NC) and MCI. Methods: Participants included 112 NC (7668 years, 63% female) and 43 MCI individuals (7767 years, 51% female) from the Boston University Alzheimer’s Disease Center. Participants completed a survey including commonly administered cognitive complaint questions (e.g., Do you have problems with your memory? Do you think that your memory is worse than two years ago?), and a neuropsychological evaluation assessing episodic memory, executive functioning, attention, processing-speed and language. Results: Among NC participants, correlation analyses, adjusting for age, sex, education and race, revealed significant associations between several questions and multiple measures of memory performance (i.e., story-memory, list-learning) with correlation coefficients ranging from -0.24 to -0.20. Questions with the strongest association included—Do you feel that your everyday life is difficult now due to your memory decline? and Do other people say you ask the same question or repeat the same story?. Complaint questions were also correlated with processing-speed (r¼-0.25, Do you often have trouble finding the word you want to use in everyday conversation?) and language (r¼-0.29, Do you lose objects more often than you did previously?) but not executive functioning or attention (p>0.05). Among the MCI participants, multiple questions were significantly correlated with multiple measures of memory with coefficients ranging from -0.48 to -0.34. Questions with the strongest association to memory measures included—Do you have difficulty remembering where you placed objects? and Do you have trouble remembering things from one moment to the next? Questions were correlated with executive function (r-0.37, Do other people say you ask the same question or repeat the same story?) but no other domains (p>0.05). Conclusions: Findings suggest methods for assessing cognitive complaints may differentially relate to objective cognitive performance. Additional research is needed to better understand the underlying neuroanatomical substrates associated with cognitive complaints and best methods for distinguishing between worried-well complaints and complaints that may represent the earliest clinical signs of an underlying neurodegenerative process. P3-093

RATES OF CONVERSION TO MCI AND ALZHEIMER’S IN THE AUSTRALIAN IMAGING, BIOMARKERS AND LIFESTYLE (AIBL) COHORT OVER 36 MONTHS

Kathryn Ellis1, Paul Maruff2, Ralph Martins3, Colin Masters4, Simon McBride5, Lance Macaulay5, Christopher Rowe6, Stephanie RaineySmith7, Alan Rembach8, Greg Savage9, Cassandra Szoeke10, Kevin Taddei11, Victor Villemagne12, Ping Zhang13, David Ames14, AIBL Research Group15, 1University of Melbourne, Mental Health Research Institute, Parkville, Australia; 2CogState Ltd, Melbourne, Australia; 3Edith Cowan University, Perth, Australia; 4Mental Health Research Institute, Melbourne, Australia; 5CSIRO, Parkville, Australia; 6CSIRO, Heidelberg, Australia; 7Edith Cowan University, Joondalup, Australia; 8Mental Health Research Institute, Parkville, Melbourne, Australia; 9Macquarie University,