Assessing Cognition. Andreana Haley, Ph.D. Department of Psychology University of Texas at Austin
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1 Assessing Cognition Andreana Haley, Ph.D. Department of Psychology University of Texas at Austin
2 Agenda Topic: Cognitive Aging Assessing Cognition Diagnosing Cognitive Impairment Dementia Diagnoses Symptoms & Neuropathology Current State of the Art in the Clinic Midlife Risk Factors for Late-life Cognitive Impairment
3 Cognition Cognition is the most important determinant of health quality of life and functional ability in older age (Gaugler et al., 2009) At any time, diminished cognitive function can cause significant psychological, social, and economic hardship (Athilingam and King, 2007) The US population is ageing fast!
4 Number of demented individuals expected to quadruple within the next 50 years Cost of care already exceeding $150 billion/ year
5 Neuropsychological Assessment Cognition Global Cognitive Functioning Memory Language Attention Executive Functioning Sensory Function Activities of Daily Living Neurobehavioral Symptoms Brain Integrity
6 Localizing Brain Function Phrenology Functional Magnetic Resonance Imaging (fmri)
7 Sensory Motor Integration Functions Executive Function Visual Integration MEMORY
8 Diagnosing Cognitive Dementia vs. Mild Cognitive Impairment Impaired Memory + One other area of cognition Impaired Activities of Daily Living Rule out reversible causes of cognitive impairment Impairment Most Common Dementias Alzheimer s Disease (AD) Vascular Dementia (VaD) Dementia with Lewy bodies (DLB) Frontotemporal Dementia (FTD) Prion Diseases Subjective Memory Complaint Corroboration by Informant Impaired Memory Intact Activities of Daily Living Rule out reversible causes of cognitive impairment
9 Alzheimer s Disease (AD) The most common form of dementia (75%) Affects 30% of all individuals over age 85 Clinical Symptoms: Prominent memory impairment Followed by language, motor control, gait disturbance Slow progression Pathologic hallmarks: Atrophy Plaques & tangles
10 Alzheimer s Disease Neuritic Plaque On the Surface Under the Microscope
11 Vascular Dementia (VaD) Caused by cerebral ischemia (stroke) Clinical Symptoms: Prominent executive dysfunction Less prominent memory/language impairment as compared with AD Unilateral sensory or motor dysfunction Rarely appears in its pure form (3%) Often contributes to the development of Alzheimer s disease Pathologic hallmark: Cerebrovascular lesions
12 Vascular Dementia (VaD) CT MRI
13 Frontotemporal Dementia (FTD) Relatively Rare Heterogeneous Clinical Symptoms: Profound changes in personality Relatively early onset Faster progression Pathologic hallmark: Circumscribed atrophy of the frontal lobes Sometimes neuronal inclusions
14 Frontotemporal Dementia (FTD) Pick Bodies On the Surface Under the Microscope
15 Dementia with Lewy Bodies (DLB) Prevalence 10-15% of all cases Parkinson s Spectrum Disorder Clinical Symptoms: Persistent memory impairment Fluctuating cognition Recurrent visual hallucinations Spontaneous Parkinsonism Pathologic hallmark: Atrophy Lewy Bodies
16 Dementia with Lewy Bodies (DLB) DLB On the Surface Under the Microscope
17 Prion Diseases (e.g., Mad Cow Disease) Extremely rare Heterogeneous (BSE, CJD, K/Juru) Infectious Clinical Symptoms Altered mental state Extremely fast progression Pathologic hallmark: Atrophy Spongy appearance of the brain matter
18 Prion Diseases CJD On the Surface Under the Microscope
19 State of the Art in the Clinic Diagnosis is based on clinical symptoms No specific in vivo biological markers (except for VaD) Approximately 90% accurate Limited treatments are available for AD, DLB, and VaD but not for FTD or CJD No cures
20 MRI Biomakers: Atrophy Normal Brain FTD Brain AD Brain
21 MRI Biomakers: White Matter Lesions
22 What then?!? Search for modifiable risk factors at midlife Focus on prevention
23
24 Obesity Body Mass Index (BMI): A measure of an adult s weight in relation to his or her height Weight (kg) / Height (cm) 2 Obesity on an Individual Level: Body Mass Index (BMI) 30 Obesity on a State level: % of all adults with BMI 30
25 Obesity Trends* Among U.S. Adults BRFSS, Obesity Trends Among U.S. Adults BRFSS (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20% 20% 24% 25% 25% 29% 30% Source: Behavioral Risk Factor Surveillance System, CDC
26 Obesity is rarely just about SIZE Obesity is related to increased risk for High blood pressure (hypertension) Elevated blood sugar levels (hyperglycemia) Dysregulated lipoprotein metabolism (dyslipidemia): Elevated triglycerides and/or Reduced HDL-cholesterol Metabolic Syndrome (MetS): 3+ of the above MetS is related to: Diabetes Cardiovascular Disease Diminished Cognitive Function
27 MetS & Cognition A staggering 34-45% of US adults fulfill criteria for MetS (Ervin, 2009) Strong evidence suggests that MetS is harmful to cognition (Kalmijn et al., 2000, Vanhanen et al., 2006, Dik et al., 2007, Yaffe et al., 2007, Gatto et al., 2008, Raffaitin et al., 2009, Yaffe et al., 2009, Akbaraly et al., 2010) The whole is greater than the sum of its parts Little is know about mechanisms Knowledge of mechanisms is critical for developing therapeutic interventions Prevention is our best defense against late-life cognitive impairment
28 How can Magnetic Resonance (Brain) Imaging Help? A window to the living human brain Biomarkers of disease and disease progression Markers of treatment response Understanding disease pathways Safe & non-invasive No radiation Contrast agents possible but not necessary Good spatial and temporal resolution Easy to repeat Extremely versatile
29 MRI MRS fmri many low resolution images (e.g., every 2 sec for 5 mins) Volume/ Atrophy ppm Chemical Composition Indirect measure of Brain Activity
30 Diffusion Tensor Tractrography
31 fmri in Clinical Neuroscience fmri has proved extremely useful in identifying abnormal brain function in at-risk individuals (Saykin et al., 1999, Bookheimer et al., 2000, Chang et al., 2001, Sweet et al., 2004, 2006) Increased task-related activation of expected regions Recruitment of additional brain regions Increased task-related de-activation of unexpected brain regions Coupled with a well-targeted behavioral challenge, fmri can unmasks early cognitive inefficiencies and compensation Coupled with other imaging modalities (e.g., MRS, ASL, vascular ultrasound), we can begin to study the underlying physiological mechanisms
32 Participants Forty right-handed individuals between the ages of 40 and MetS (ages 47±6) 21 Healthy Controls (50±5) Free of neurological & psychiatric disease Ethnically diverse Cognitively normal Mean full-scale IQ = 115.0±10.5 No significant group differences in age, sex, education or any other cognitive measure
33 Methods General health assessment (height & weight, blood pressure, lipid profile, and fasting glucose) Full Neuropsychological Evaluation Neuroimaging (Structural, fmri) 2-Back Condition Eight a priori Regions of Interest (ROIs) 0-Back Condition (targets in red) time
34 Results
35 Conclusions fmri is sensitive to brain changes related to MetS Changes may indicate early vulnerability of the frontoparietal attention/executive system (why not greater efficiency of processing?!?) In younger populations at CVD risk, within the a priori ROIs activation = performance & reaction times for everyone In older populations with CVD, within the same ROIs task-related brain activation = large vessel atherosclerosis, endothelial function & clinically significant cognitive impairment
36
37 Mechanisms MetS IS NO BOLD Cog
38 Insulin Sensitivity & BOLD in obesity Insulin Sensitivity Obesity BOLD Gonzales et al. (2010), Obesity, 18,
39 Endothelial function & BOLD in middle age Gonzales et al. (2010), Brain and Cognition, 73,
40 Future Directions Test if the changes are global or specific to cognition and the fronto-parietal network Check for evidence of cerebrovascular decoupling Validate the alterations as markers of brain vulnerability in longitudinal studies Explore the underlying mechanisms by assessing volume, cerebral perfusion and neurochemistry MetS IS plasticity of glutamate receptors Cog Test the efficacy of early interventions
41 Mechanisms Obesity Neurochemisty Cognitive function
42 Neurochemical Alterations in Obesity General health assessment (height & weight, blood pressure, lipid profile, and fasting glucose) Full Neuropsychological Evaluation Neuroimaging (Structural, MRS) ROI Borders on High Resolution Anatomy *
43 Interpretation mi is associated with cognitive impairment in Down Syndrome Alzheimer s Disease Mild Cognitive Impairment Interpreted as a sign of Gliosis Disturbance in the second messenger signaling involving inositol tri-phosphate Disturbance in fluid homeostasis mi and abnormal inositol phospholipid metabolism have been reported in diabetes mellitus
44 Obesity & Cognitive Function mi Obesity Cognitive Function
45 Obesity, Dyslipidemia & mi Dyslipidemia Obesity mi
46 Future Directions Validate the alterations as markers of brain vulnerability in longitudinal studies Test the efficacy of early interventions
47 It is a collaborative effort Clinical Neuroscience Lab Mitzi Gonzales, B.A. Danielle Eagan, M.A. Katy Goudarzi, M.D. Sonya Kaur, B.A. Fedora Biney, B.A. Rachel Cooper, B.A. Sandra Stautberg, B.A. Furquan Shah, B.S. Cardiovascular Aging Lab Hirofumi Tanaka, Ph.D. Takashi Tarumi, M.A. June Sugawara, Ph.D. Steven Miles, B.S.
48 Thank you!
49 BOLD signal Blood Oxygen Level Dependent signal neural activity blood flow oxyhemoglobin MR signal Source: fmrib Brief Introduction to fmri
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