- Email: [email protected]
Transcranial Doppler cerebral blood flow velocity and cognitive function: Results from the Einstein Aging Study (EAS)
P774 P4-187
Poster Presentations: P4 AN UPDATED SYSTEMATIC REVIEW OF THE IMPACT OF MEDICATIONS WITH ANTICHOLINERGIC ACTIVITY ON COGNITIVE FUNCTION AND MORTALITY
Ian Maidment1, Wei-Yee Chan2, Nelson Bua2, Phyo Myint2, Noll Campbell3, Malaz Boustani4, Chun Shing Kwok2, Chris Fox5, 1Aston University, Birmingham, England, United Kingdom; 2Medical School, Norwich, England, United Kingdom; 3Regenstrief Institute, Indianapolis, Indiana, United States; 4Indiana University School of Medicine, Indianapolis, Indiana, United States; 5University of East Anglia Medical School, Norfolk, England, United Kingdom. Contact e-mail: i.maidment@ aston.ac.uk Background: An estimated 18% of older ( 65) adults suffer from mild cognitive impairment (MCI). More than half will progress to dementia within 5 years. Primary prevention may be by recognition of the true burden of anticholinergic drugs on cognition and avoidance wherever possible. This project aimed to systematically review the literature to update a widely used scale that assesses anti-cholinergic burden (ACB scale) and establish the impact of drugs with anticholinergic properties on cognitive function in patients over the age of 18 without a diagnosis of dementia. Methods: Study selection We searched MEDLINE, the Cochrane Collaboration Registry for Randomised Controlled Trials, CINAHL and the FDA AERS from January 2002 to January 2013 for RCTs, systematic reviews, cross-sectional studies, case-control studies and observational cohort studies that evaluated the anticholinergic activity of medications and their impact on cognitive function of adults. Exclusion criteria included review articles, case studies, case series, editorials, papers not in English language and animal studies. Data extraction Extraction included measure of anti-cholinergic activity and its association with cognitive outcomes and mortality. Critical appraisal of internal validity of the studies was done with quality rating tools for different study designs: Cochrane Collaboration tool for assessing risk of bias in RCTs, the appropriate Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies. Results: Anti-cholinergic activity was measured in a number of ways though serum anti-cholinergic assay remained a common method. Various anti-cholinergic drug scales were used to improve quantification of anti-cholinergic burden in patients. The MMSE was the most common method to assess cognitive function. All studies continue to support previous findings of higher exposure being associated with cognitive impairment. Additional measures included a number of performed physical functioning skills. Studies which calculated association with mortality disagreed, one finding significant association whilst another did not. Conclusions: Medicines with anti-cholinergic activity have a negative effect on cognition. A regularly updated tool for clinicians to recognise all drugs with anti-cholinergic burden may improve cognition; especially in patients requiring polypharmacy. P4-188
THE TRAJECTORY-RELATED EARLY ALZHEIMER’S DATABASE (TREAD) STUDY
David Darby1, Amy Brodtmann1, Michael Woodward1, Colin Masters2, Florey Institute of Neuroscience and Mental Health, Parkville VIC, Australia; 2University of Melbourne, Melbourne, VIC, Australia. Contact e-mail: [email protected] 1
Background: Early detection of Alzheimer’s disease (AD) in the prodromal stages is now critical to test promising disease modifying therapies at a time when single mechanism therapies are likely to be most effective. Identification of such early prodromal patients is problematic. Serial computerized cognitive testing is a potentially cost-effective community screening approach. Methods: The TREAD study is a Melbourne-based initiative that aims to recruit 10,000 community dwelling volunteers age 50 and over, who are willing to perform internet-based remote computerized cognitive testing serially in order to detect decline in episodic memory. When detected, they are offered medical evaluation for identifiable causes, and if none are detected, then are offered biomarker (CSF, amyloid-PET) and benchmarking (neuropsychological, MRI, FDG-PET) evaluations to obtain baseline measures for future trials (and determination of pre-trial trajectories). Such well-characterized volunteers are then made available for clinical trial recruitment. Results: Recruitment started on 21 Dec 2012 with a single radio interview, with over 520 registered participants by Feb 2013. Baseline demographic data: Mean age
60.0 years (SD 0.32), mean education 13.5 years (SD 0.15), males 36%, family history of AD 26%, right handed 89%. Mean Penn State Worry Questionnaire-15 29.2/90 (SD 0.62) suggestive of at most mild anxiety. Mean Patient Health Questionnaire-9 2.4/27 (SD 0.12) indicative of no depression. Subjective memory complaints mean 2.1/10 (SD 0.1) consistent with minimal complaints. Testing used both various software engines - 72% could test using a FLASH-based engine, 95% could use a javascript-based engine. Conclusions: Interest is high amongst community dwelling participants for memory screening despite being forewarned that they will be told if found to be declining. Browser and technical issues have dominated early adoption of this approach but appear to be surmountable. Target recruitment of much larger numbers appears feasible and will be attempted over the next months. P4-189
ACTIVITIES OF DAILY LIVING IN MCI AND ITS PROGRESSION TO DEMENTIA
YongSoo Shim1, Bora Yoon2, Yun Jeong Hong3, Dong Won Yang4, 1The Catholic University of Korea, Gyeonggi-do, South Korea; 2Konyang University Hospital, Daejeon, South Korea; 3Hyoja Geriatric Hospital, Yong-In, South Korea; 4Seoul St.Mary’s Hospital, Seoul, South Korea. Contact e-mail: [email protected] Background: Mild cognitive impairment (MCI) is considered as prodromal state to dementia. Activities of daily living (ADL) are generally preserved, but instrumental ADL (IADL) can be minimally impaired. There is no consensus regarding the relationship between the deterioration of IADL and the progression to dementia. In this study, we reviewed the follow-up data of MCI patients and investigated with which IADL items we can predict dementia. Methods: By using the database of clinical research center for dementia of South Korea, we analyzed the information of 778 patients who were diagnosed as MCI at the first visit and performed follow-up evaluations. Clinicians diagnosed the patients as MCI or dementia such as Alzheimer’s disease (AD) at the followup visits, according to the impairment of ADL or deterioration of clinical dementia rating (CDR). The distributions of age, gender, education years, disease duration, and baseline scores of mini-mental state examination (MMSE), CDR-sum of boxes (SOB), and Hachinski ischemic scale was compared between the remained and progressed patients. Mean scores and frequencies of every 15 items of Seoul IADL at the baseline and follow-up evaluations were also compared. Results: Among 778 follow-up patients, 214 patients (27.51%), including 199 AD patients, were progressed into dementia. Mean follow-up period was 1.42 6 0.72 years. At the baseline, patients with progressed into dementia (72.06 66.86) were older than patients with remained in MCI (70.07 67.53, p¼0.001) and showed more severe impairments in scores of MMSE, CDRSOB, and Seoul IADL (all, p<0.001). The others were not different. Frequencies and scores for the follow-up changes of all 15 Seoul IADL items were different between MCI remained and AD progressed patients (all, p<0.001). At the baseline, using telephone (scale; p¼0.001, frequency; p¼0.003), using public transportation (scale; p¼0.012, frequency; p¼0.037), managing medications (all, p<0.001), financial management (scale; p¼0.002, frequency; p¼0.005), finding belongings (scale; p¼0.007, frequency; p¼0.023), keeping appointments (scale; p¼0.001, frequency; p<0.001), and discussing current events (all, p<0.001) were different between two groups. Conclusions: We suggest that when individuals with MCI show the impairments or deteriorations in their performance of IADL, this is predictive of dementia onset. P4-190
TRANSCRANIAL DOPPLER CEREBRAL BLOOD FLOW VELOCITY AND COGNITIVE FUNCTION: RESULTS FROM THE EINSTEIN AGING STUDY (EAS)
Ali Ezzati1, Carol Derby2, Mindy Katz2, Molly Zimmerman2, Richard Lipton2, Digna Cabral3, Tatjana Rundek4, 1Albert Einstein College of Medicine, Bronx, New York, United States; 2Albert Einstein College of Medicine, Bronx, New York, United States; 3Miller School of Medicine, University of Miami, Miami, Florida, United States; 4Miller School of Medicine, University of Miami, Miami, Florida, United States. Contact e-mail: [email protected] Background: Reduced cerebrovascular perfusion has been associated with cognitive decline and dementia. However there are few data regarding the
Poster Presentations: P4 relation of cerebrovascular perfusion to domains of cognitive performance in non-demented population based samples due in part to feasibility issues and cost of P.E.T. or MRI. Transcranial Doppler (TCD) ultrasound provides an inexpensive, rapid, non-invasive technique for assessing cerebrovascular function. We examined the cross-sectional associations of TCD measures of blood flow velocities in arteries of the circle of Willis to cognitive performance in participants in the EAS cohort. Methods: Analyses included 97 non-demented, community residing elderly, age 3 70. TCD was performed by a trained ultrasound technician using a standardized and validated research protocol during the annual clinic visit which included neuropsychological testing and neurological exams. The group was 52% female, mean age 80.9 (65.6) years, mean education 15 years. Cognitive domain evaluation included episodic memory (Free Recall from Free and Cued Selective Reminding Test-FR-FCSRT and WMS-R Logical Memory I subtest -LM), semantic memory (category fluency CF), executive function (WAIS-III digit symbol substitution test-DSST; Trail-Making Test-B TMT-B), and language (phonemic fluency-FAS).We computed the mean of right and left flow velocities (MFV) for each vessel. Spearman’s correlation coefficients were used to examine the relation of MFV in the anterior (ACA_MFV), posterior (PCA_MFV) and middle (MCA_MFV) cerebral arteries to cognitive performance. Linear regression analyses were used to determine whether associations persisted after adjustment for age, sex and education. Results: There was a consistent pattern showing a positive correlation between CF, DSST, TMT-B and FAS with ACA_MFV and PCA_MFV while memory tests were not correlated with MFV. The MCA-MFV was not correlated with any cognitive measures. The associations of ACA_MFV and PCA_MFV with cognition remained after adjustment for age sex, and education. Conclusions: Cerebral blood flow appears to be more highly correlated with performance on tests of executive function and language than with tests of episodic memory. This is consistent with prior information suggesting a link between vascular processes and frontal executive function. TCD may be useful for distinguishing persons at risk for amnestic versus non-amnestic mild cognitive impairment. Longitudinal data are needed to confirm this hypothesis. Spearman’s Correlation Coefficient (p-value) N¼97 EAS participants MFV
TMTB speed PCA_MFV 0.14 (.17) 0.12 (.25) 0.41 (<0.001) 0.23 (0.03) 0.23 (0.03) ACA_MFV 0.14 (0.19) -0.027 (.80) 0.35 (0.001) 0.30 (0.004) 0.25 (0.14) MCA_MFV -0.024 (0.82) -0.095(.36) 0.14 (0.17) 0.057 (0.59) 0.085 (.41)
P4-191
FCSRT-FR
LM
CF
DSST
SYSTEMIC INFLAMMATORY RESPONSES TO STRESS AND ITS IMPACT ON COGNITION IN PEOPLE WITH MILD COGNITIVE IMPAIRMENT
Rebecca Sussams1, Wolff Schlotz2, Hugh Perry1, Hopkins Viv3, Davies Lynn3, Ceri Rayner3, Isabel Lewzey3, Anna Christodoulou4, Brady MacFarlene3, Richard Sharples3, Clive Holmes4, 1University of Southampton, Southampton, United Kingdom; 2University of Regensburg, Regensburg, Germany; 3Southern Health NHS Foundation Trust, Southampton, United Kingdom; 4Southern Health NHS Foundation, Southampton, United Kingdom. Contact e-mail: becky.sussams@ southernhealth.nhs.uk Background: Subjects with amnestic Mild Cognitive Impairment (aMCI) do not inevitably show cognitive decline or convert to Alzheimer’s Disease supporting the hypothesis that secondary events are crucial in the conversion process. The purpose of this study is to examine whether stress (psychological and physical) is an important contributor to the worsening of cognitive decline in aMCI subjects. We hypothesise that cognitive decline is due, in part, to the prolonged stress-induced production of pro-inflammatory cytokines. Methods: This is a longitudinal observational study assessing the association between cognitive decline and the degree of stress in 140 aMCI subjects and 70 cognitively intact control subjects. The primary hypothesis is that psychological life stress, as measured by the RLCQ, is associated with worsened cognitive decline, as measured by a comparison of the change in the FCSRT-IR score, over an 18 month follow up period. Secondary outcomes include difference in change in the TMT scores; Verbal Fluency scores; MoCA score; Digit
P775
Symbol Substitution Test; conversion to Dementia; the Geriatric Depression Scale; Sickness Behaviour Scale and quality of life (EQ-5D). Other exploratory measures of stress include salivary cortisol levels; the PSS, Trauma History, the CSSS and physical stressors including infections and physical trauma. Possible modulators of the stress response include social support (MOS-SSS); coping skills (CISS) and personality (NEO FFI - Neuroticism scale). Biological outcomes include changes in blood levels of inflammatory markers and immunophenotyping of peripheral blood mononuclear cells. Results: To date 26 aMCI and 32 controls have been recruited (43% male). Common major life stressors reported include death of a loved one, dementia caregiving, and major illness. Reported prevalence of stressors was high within this subject group with 90% of subjects reporting 1 or more stressors; 71% reporting 2 or more stressors and 50% reporting 3 or more stressors in the previous 6 months. Comparisons between aMCI and controls will be presented. Conclusions: Life events causing stress appear sufficiently common within this subject group to warrant further investigation into the impact of stress upon cognitive decline. P4-192
BRAIN HYPOPERFUSION AND NEUROVASCULAR DECOUPLING IN AMNESTIC MILD COGNITIVE IMPAIRMENT
Rong Zhang1, Jie Liu1, Ayaz Khan2, Benjamin Tseng3, Takashi Tarumi1, Kyle Armstrong1, Candace Hill4, Kristin Martin-Cook5, Myron Weiner5, Munro Cullum5, 1Institute for Exercise and Environmental Medicine,Texas Health Presbyterian Hospital Dallas, Dallas, Texas, United States; 2IEEM, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, United States; 3 Institute for Exercise and Environmental Medicine, Dallas, Texas, United States; 4IEEM, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, United States; 5Alzheimer’s Disease Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States. Contact e-mail: [email protected] Background: Brain hypoperfusion and hypometabolism may occur in patients with amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer disease (AD). However, it is not clear if these changes reflect simply a reduced metabolic demand leading to reduction in brain perfusion or reveal impaired cerebral autoregulatory mechanisms which control brain neurovascular coupling. The purpose of this study is to measure cerebral blood flow and brain tissue oxygenation simultaneously to assess brain perfusion and neurovascular coupling in patients with aMCI. Methods: Thirty-two aMCI patients and 21 normal subjects participated. Total cerebral blood flow (TCBF), brain tissue oxygenation index (TOI), and brain volume were measured using color-coded duplex ultrasonography (CDUS), near-infrared spectroscopy (NIRS), and magnetic resonance imaging (MRI). TCBF was normalized by brain tissue volume (nTCBF). Arterial blood oxygen saturation (SaO 2) was measured using pulse oximeter. Cerebral metabolic rate of oxygen utilization (CMRO 2) was calculated as CMRO 2 ¼ nTCBF3(SaO 2 -TOI) 3 k based on Fick’s law (k is a constant related to oxygen capacity of blood and brain tissue density). Results: For group comparisons, nTCBF was reduced by 9% and CMRO 2 by 11% in aMCI relative to normal controls (P < 0.05) No differences in total brain volume were observed. nTCBF was correlated with gray matter volume (r ¼ 0.47, P < 0.05) and CMRO 2 (r ¼ 0.57, P < 0.05, reflecting neurovascular coupling) in the normal controls, but not in aMCI. Conclusions: Brain hypoperfusion, oxygen hypometabolism and neurovascular decoupling are observed in patients with aMCI. These findings suggest that impairment of cerebrovascular function occur early at prodromal stage of AD which can be assessed using low cost and bed-side available ultrasonography and NIRS technology. P4-193
TWO-YEAR OUTCOME IN OLDER ADULTS WITH COGNITIVE COMPLAINTS: RELATION TO BASELINE COGNITION, SELF- AND INFORMANT RATINGS, GENETICS AND IMAGING
Andrew Saykin1, Shannon Risacher1, Brenna McDonald2, John West2, Eileen Tallman1, Laura Flashman3, Heather Wishart3, Laura Rabin4, Nadia Pare5, Darren O’Neill2, Sungeun Kim1, Yang Wang1, Li Shen1, Robert Santulli3, Martin Farlow2, 1Indiana University School of Medicine, Indianapolis, Indiana, United States; 2Indiana Universitty School of
Poster Presentations: P4 AN UPDATED SYSTEMATIC REVIEW OF THE IMPACT OF MEDICATIONS WITH ANTICHOLINERGIC ACTIVITY ON COGNITIVE FUNCTION AND MORTALITY
Ian Maidment1, Wei-Yee Chan2, Nelson Bua2, Phyo Myint2, Noll Campbell3, Malaz Boustani4, Chun Shing Kwok2, Chris Fox5, 1Aston University, Birmingham, England, United Kingdom; 2Medical School, Norwich, England, United Kingdom; 3Regenstrief Institute, Indianapolis, Indiana, United States; 4Indiana University School of Medicine, Indianapolis, Indiana, United States; 5University of East Anglia Medical School, Norfolk, England, United Kingdom. Contact e-mail: i.maidment@ aston.ac.uk Background: An estimated 18% of older ( 65) adults suffer from mild cognitive impairment (MCI). More than half will progress to dementia within 5 years. Primary prevention may be by recognition of the true burden of anticholinergic drugs on cognition and avoidance wherever possible. This project aimed to systematically review the literature to update a widely used scale that assesses anti-cholinergic burden (ACB scale) and establish the impact of drugs with anticholinergic properties on cognitive function in patients over the age of 18 without a diagnosis of dementia. Methods: Study selection We searched MEDLINE, the Cochrane Collaboration Registry for Randomised Controlled Trials, CINAHL and the FDA AERS from January 2002 to January 2013 for RCTs, systematic reviews, cross-sectional studies, case-control studies and observational cohort studies that evaluated the anticholinergic activity of medications and their impact on cognitive function of adults. Exclusion criteria included review articles, case studies, case series, editorials, papers not in English language and animal studies. Data extraction Extraction included measure of anti-cholinergic activity and its association with cognitive outcomes and mortality. Critical appraisal of internal validity of the studies was done with quality rating tools for different study designs: Cochrane Collaboration tool for assessing risk of bias in RCTs, the appropriate Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies. Results: Anti-cholinergic activity was measured in a number of ways though serum anti-cholinergic assay remained a common method. Various anti-cholinergic drug scales were used to improve quantification of anti-cholinergic burden in patients. The MMSE was the most common method to assess cognitive function. All studies continue to support previous findings of higher exposure being associated with cognitive impairment. Additional measures included a number of performed physical functioning skills. Studies which calculated association with mortality disagreed, one finding significant association whilst another did not. Conclusions: Medicines with anti-cholinergic activity have a negative effect on cognition. A regularly updated tool for clinicians to recognise all drugs with anti-cholinergic burden may improve cognition; especially in patients requiring polypharmacy. P4-188
THE TRAJECTORY-RELATED EARLY ALZHEIMER’S DATABASE (TREAD) STUDY
David Darby1, Amy Brodtmann1, Michael Woodward1, Colin Masters2, Florey Institute of Neuroscience and Mental Health, Parkville VIC, Australia; 2University of Melbourne, Melbourne, VIC, Australia. Contact e-mail: [email protected] 1
Background: Early detection of Alzheimer’s disease (AD) in the prodromal stages is now critical to test promising disease modifying therapies at a time when single mechanism therapies are likely to be most effective. Identification of such early prodromal patients is problematic. Serial computerized cognitive testing is a potentially cost-effective community screening approach. Methods: The TREAD study is a Melbourne-based initiative that aims to recruit 10,000 community dwelling volunteers age 50 and over, who are willing to perform internet-based remote computerized cognitive testing serially in order to detect decline in episodic memory. When detected, they are offered medical evaluation for identifiable causes, and if none are detected, then are offered biomarker (CSF, amyloid-PET) and benchmarking (neuropsychological, MRI, FDG-PET) evaluations to obtain baseline measures for future trials (and determination of pre-trial trajectories). Such well-characterized volunteers are then made available for clinical trial recruitment. Results: Recruitment started on 21 Dec 2012 with a single radio interview, with over 520 registered participants by Feb 2013. Baseline demographic data: Mean age
60.0 years (SD 0.32), mean education 13.5 years (SD 0.15), males 36%, family history of AD 26%, right handed 89%. Mean Penn State Worry Questionnaire-15 29.2/90 (SD 0.62) suggestive of at most mild anxiety. Mean Patient Health Questionnaire-9 2.4/27 (SD 0.12) indicative of no depression. Subjective memory complaints mean 2.1/10 (SD 0.1) consistent with minimal complaints. Testing used both various software engines - 72% could test using a FLASH-based engine, 95% could use a javascript-based engine. Conclusions: Interest is high amongst community dwelling participants for memory screening despite being forewarned that they will be told if found to be declining. Browser and technical issues have dominated early adoption of this approach but appear to be surmountable. Target recruitment of much larger numbers appears feasible and will be attempted over the next months. P4-189
ACTIVITIES OF DAILY LIVING IN MCI AND ITS PROGRESSION TO DEMENTIA
YongSoo Shim1, Bora Yoon2, Yun Jeong Hong3, Dong Won Yang4, 1The Catholic University of Korea, Gyeonggi-do, South Korea; 2Konyang University Hospital, Daejeon, South Korea; 3Hyoja Geriatric Hospital, Yong-In, South Korea; 4Seoul St.Mary’s Hospital, Seoul, South Korea. Contact e-mail: [email protected] Background: Mild cognitive impairment (MCI) is considered as prodromal state to dementia. Activities of daily living (ADL) are generally preserved, but instrumental ADL (IADL) can be minimally impaired. There is no consensus regarding the relationship between the deterioration of IADL and the progression to dementia. In this study, we reviewed the follow-up data of MCI patients and investigated with which IADL items we can predict dementia. Methods: By using the database of clinical research center for dementia of South Korea, we analyzed the information of 778 patients who were diagnosed as MCI at the first visit and performed follow-up evaluations. Clinicians diagnosed the patients as MCI or dementia such as Alzheimer’s disease (AD) at the followup visits, according to the impairment of ADL or deterioration of clinical dementia rating (CDR). The distributions of age, gender, education years, disease duration, and baseline scores of mini-mental state examination (MMSE), CDR-sum of boxes (SOB), and Hachinski ischemic scale was compared between the remained and progressed patients. Mean scores and frequencies of every 15 items of Seoul IADL at the baseline and follow-up evaluations were also compared. Results: Among 778 follow-up patients, 214 patients (27.51%), including 199 AD patients, were progressed into dementia. Mean follow-up period was 1.42 6 0.72 years. At the baseline, patients with progressed into dementia (72.06 66.86) were older than patients with remained in MCI (70.07 67.53, p¼0.001) and showed more severe impairments in scores of MMSE, CDRSOB, and Seoul IADL (all, p<0.001). The others were not different. Frequencies and scores for the follow-up changes of all 15 Seoul IADL items were different between MCI remained and AD progressed patients (all, p<0.001). At the baseline, using telephone (scale; p¼0.001, frequency; p¼0.003), using public transportation (scale; p¼0.012, frequency; p¼0.037), managing medications (all, p<0.001), financial management (scale; p¼0.002, frequency; p¼0.005), finding belongings (scale; p¼0.007, frequency; p¼0.023), keeping appointments (scale; p¼0.001, frequency; p<0.001), and discussing current events (all, p<0.001) were different between two groups. Conclusions: We suggest that when individuals with MCI show the impairments or deteriorations in their performance of IADL, this is predictive of dementia onset. P4-190
TRANSCRANIAL DOPPLER CEREBRAL BLOOD FLOW VELOCITY AND COGNITIVE FUNCTION: RESULTS FROM THE EINSTEIN AGING STUDY (EAS)
Ali Ezzati1, Carol Derby2, Mindy Katz2, Molly Zimmerman2, Richard Lipton2, Digna Cabral3, Tatjana Rundek4, 1Albert Einstein College of Medicine, Bronx, New York, United States; 2Albert Einstein College of Medicine, Bronx, New York, United States; 3Miller School of Medicine, University of Miami, Miami, Florida, United States; 4Miller School of Medicine, University of Miami, Miami, Florida, United States. Contact e-mail: [email protected] Background: Reduced cerebrovascular perfusion has been associated with cognitive decline and dementia. However there are few data regarding the
Poster Presentations: P4 relation of cerebrovascular perfusion to domains of cognitive performance in non-demented population based samples due in part to feasibility issues and cost of P.E.T. or MRI. Transcranial Doppler (TCD) ultrasound provides an inexpensive, rapid, non-invasive technique for assessing cerebrovascular function. We examined the cross-sectional associations of TCD measures of blood flow velocities in arteries of the circle of Willis to cognitive performance in participants in the EAS cohort. Methods: Analyses included 97 non-demented, community residing elderly, age 3 70. TCD was performed by a trained ultrasound technician using a standardized and validated research protocol during the annual clinic visit which included neuropsychological testing and neurological exams. The group was 52% female, mean age 80.9 (65.6) years, mean education 15 years. Cognitive domain evaluation included episodic memory (Free Recall from Free and Cued Selective Reminding Test-FR-FCSRT and WMS-R Logical Memory I subtest -LM), semantic memory (category fluency CF), executive function (WAIS-III digit symbol substitution test-DSST; Trail-Making Test-B TMT-B), and language (phonemic fluency-FAS).We computed the mean of right and left flow velocities (MFV) for each vessel. Spearman’s correlation coefficients were used to examine the relation of MFV in the anterior (ACA_MFV), posterior (PCA_MFV) and middle (MCA_MFV) cerebral arteries to cognitive performance. Linear regression analyses were used to determine whether associations persisted after adjustment for age, sex and education. Results: There was a consistent pattern showing a positive correlation between CF, DSST, TMT-B and FAS with ACA_MFV and PCA_MFV while memory tests were not correlated with MFV. The MCA-MFV was not correlated with any cognitive measures. The associations of ACA_MFV and PCA_MFV with cognition remained after adjustment for age sex, and education. Conclusions: Cerebral blood flow appears to be more highly correlated with performance on tests of executive function and language than with tests of episodic memory. This is consistent with prior information suggesting a link between vascular processes and frontal executive function. TCD may be useful for distinguishing persons at risk for amnestic versus non-amnestic mild cognitive impairment. Longitudinal data are needed to confirm this hypothesis. Spearman’s Correlation Coefficient (p-value) N¼97 EAS participants MFV
TMTB speed PCA_MFV 0.14 (.17) 0.12 (.25) 0.41 (<0.001) 0.23 (0.03) 0.23 (0.03) ACA_MFV 0.14 (0.19) -0.027 (.80) 0.35 (0.001) 0.30 (0.004) 0.25 (0.14) MCA_MFV -0.024 (0.82) -0.095(.36) 0.14 (0.17) 0.057 (0.59) 0.085 (.41)
P4-191
FCSRT-FR
LM
CF
DSST
SYSTEMIC INFLAMMATORY RESPONSES TO STRESS AND ITS IMPACT ON COGNITION IN PEOPLE WITH MILD COGNITIVE IMPAIRMENT
Rebecca Sussams1, Wolff Schlotz2, Hugh Perry1, Hopkins Viv3, Davies Lynn3, Ceri Rayner3, Isabel Lewzey3, Anna Christodoulou4, Brady MacFarlene3, Richard Sharples3, Clive Holmes4, 1University of Southampton, Southampton, United Kingdom; 2University of Regensburg, Regensburg, Germany; 3Southern Health NHS Foundation Trust, Southampton, United Kingdom; 4Southern Health NHS Foundation, Southampton, United Kingdom. Contact e-mail: becky.sussams@ southernhealth.nhs.uk Background: Subjects with amnestic Mild Cognitive Impairment (aMCI) do not inevitably show cognitive decline or convert to Alzheimer’s Disease supporting the hypothesis that secondary events are crucial in the conversion process. The purpose of this study is to examine whether stress (psychological and physical) is an important contributor to the worsening of cognitive decline in aMCI subjects. We hypothesise that cognitive decline is due, in part, to the prolonged stress-induced production of pro-inflammatory cytokines. Methods: This is a longitudinal observational study assessing the association between cognitive decline and the degree of stress in 140 aMCI subjects and 70 cognitively intact control subjects. The primary hypothesis is that psychological life stress, as measured by the RLCQ, is associated with worsened cognitive decline, as measured by a comparison of the change in the FCSRT-IR score, over an 18 month follow up period. Secondary outcomes include difference in change in the TMT scores; Verbal Fluency scores; MoCA score; Digit
P775
Symbol Substitution Test; conversion to Dementia; the Geriatric Depression Scale; Sickness Behaviour Scale and quality of life (EQ-5D). Other exploratory measures of stress include salivary cortisol levels; the PSS, Trauma History, the CSSS and physical stressors including infections and physical trauma. Possible modulators of the stress response include social support (MOS-SSS); coping skills (CISS) and personality (NEO FFI - Neuroticism scale). Biological outcomes include changes in blood levels of inflammatory markers and immunophenotyping of peripheral blood mononuclear cells. Results: To date 26 aMCI and 32 controls have been recruited (43% male). Common major life stressors reported include death of a loved one, dementia caregiving, and major illness. Reported prevalence of stressors was high within this subject group with 90% of subjects reporting 1 or more stressors; 71% reporting 2 or more stressors and 50% reporting 3 or more stressors in the previous 6 months. Comparisons between aMCI and controls will be presented. Conclusions: Life events causing stress appear sufficiently common within this subject group to warrant further investigation into the impact of stress upon cognitive decline. P4-192
BRAIN HYPOPERFUSION AND NEUROVASCULAR DECOUPLING IN AMNESTIC MILD COGNITIVE IMPAIRMENT
Rong Zhang1, Jie Liu1, Ayaz Khan2, Benjamin Tseng3, Takashi Tarumi1, Kyle Armstrong1, Candace Hill4, Kristin Martin-Cook5, Myron Weiner5, Munro Cullum5, 1Institute for Exercise and Environmental Medicine,Texas Health Presbyterian Hospital Dallas, Dallas, Texas, United States; 2IEEM, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, United States; 3 Institute for Exercise and Environmental Medicine, Dallas, Texas, United States; 4IEEM, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, United States; 5Alzheimer’s Disease Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States. Contact e-mail: [email protected] Background: Brain hypoperfusion and hypometabolism may occur in patients with amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer disease (AD). However, it is not clear if these changes reflect simply a reduced metabolic demand leading to reduction in brain perfusion or reveal impaired cerebral autoregulatory mechanisms which control brain neurovascular coupling. The purpose of this study is to measure cerebral blood flow and brain tissue oxygenation simultaneously to assess brain perfusion and neurovascular coupling in patients with aMCI. Methods: Thirty-two aMCI patients and 21 normal subjects participated. Total cerebral blood flow (TCBF), brain tissue oxygenation index (TOI), and brain volume were measured using color-coded duplex ultrasonography (CDUS), near-infrared spectroscopy (NIRS), and magnetic resonance imaging (MRI). TCBF was normalized by brain tissue volume (nTCBF). Arterial blood oxygen saturation (SaO 2) was measured using pulse oximeter. Cerebral metabolic rate of oxygen utilization (CMRO 2) was calculated as CMRO 2 ¼ nTCBF3(SaO 2 -TOI) 3 k based on Fick’s law (k is a constant related to oxygen capacity of blood and brain tissue density). Results: For group comparisons, nTCBF was reduced by 9% and CMRO 2 by 11% in aMCI relative to normal controls (P < 0.05) No differences in total brain volume were observed. nTCBF was correlated with gray matter volume (r ¼ 0.47, P < 0.05) and CMRO 2 (r ¼ 0.57, P < 0.05, reflecting neurovascular coupling) in the normal controls, but not in aMCI. Conclusions: Brain hypoperfusion, oxygen hypometabolism and neurovascular decoupling are observed in patients with aMCI. These findings suggest that impairment of cerebrovascular function occur early at prodromal stage of AD which can be assessed using low cost and bed-side available ultrasonography and NIRS technology. P4-193
TWO-YEAR OUTCOME IN OLDER ADULTS WITH COGNITIVE COMPLAINTS: RELATION TO BASELINE COGNITION, SELF- AND INFORMANT RATINGS, GENETICS AND IMAGING
Andrew Saykin1, Shannon Risacher1, Brenna McDonald2, John West2, Eileen Tallman1, Laura Flashman3, Heather Wishart3, Laura Rabin4, Nadia Pare5, Darren O’Neill2, Sungeun Kim1, Yang Wang1, Li Shen1, Robert Santulli3, Martin Farlow2, 1Indiana University School of Medicine, Indianapolis, Indiana, United States; 2Indiana Universitty School of