Is It Alzheimer’s? The Latest Update on Optimal Evaluation and Treatment of Patients with Memory Loss Majid Fotuhi, MD PhD March 5, 2014

New Discoveries 2

65 year old woman with history of depression and OSA presents with memory loss and concern for Alzheimer’s disease  Was working full time until two years ago at SS, as a manager and program analyst  Husband had severe respiratory disease and she was taking care of him until three months ago, when he died  Family had noticed a progressive memory loss for approximately 1-2 years (since retirement)  Spends much of her time at home, with no social activities or interest in taking on new hobbies  Sister is convinced she has Alzheimer’s disease  Was referred to NeurExpand Brain Center for further evaluation and treatment  Is it Alzheimer’s? What can be done for her? 3

Immediate Memory Letter FluencySustained AttentionProcessing Speed Delayed Memory Baseline NeuroCognitive Assessments April 18,

MoodAnxietyInsomnia Cognitive InhibitionCognitive flexibilityInhibition & flexibility Baseline NeuroCognitive Assessment April 18,

Objectives  What is the difference between memory loss, MCI, and Alzheimer’s?  Why does the brain shrink with aging?  Can we reverse the effects of aging on the brain?  Can we grow the size of our brain?  Can we expand our cognitive performance and brain size? The Brain Fitness Program 6

Objectives  What is the difference between memory loss, MCI, and Alzheimer’s?  Why does the brain shrink with aging?  Can we reverse the effects of aging on the brain?  Can we grow the size of our brain?  Can we expand our cognitive performance and brain size? The Brain Fitness Program 7

MCI DEMENTIA 8

Memory Lapses Memory Lapses or Alzheimer’s? Age-Associated Memory Impairment MCI Alzheimer’s 9

Short-term: Hippocampus Long-term: Cortex Cortex Hippocampus 10

Beautiful Neurons in Hippocampus 11

Hippocampal Atrophy is the Most Robust Marker for Dementia Duara et al., Neurology 71:1986–92,

Objectives  What is the difference between memory loss, MCI, and Alzheimer’s?  Why does the brain shrink with aging?  Can we reverse the effects of aging on the brain?  Can we grow the size of our brain?  Can we expand our cognitive performance and brain size? The Brain Fitness Program 13

Overlapping Causes of Atrophy in Hippocampus Obesity-Diabetes Stroke Sleep Apnea Concussion AD Inflammation Stress 14

Brain is a Highly Vascular Organ Zlokovic et al. Neurosurgery 43(4), 877–78,

Vascular Brain Atrophy in OSA Am J Respir Crit Care Med 2002; 166:1382–7 16

Obesity Shrinks the Brain  Associated with reduced brain volume Ward, et al., 2005  Slows cognitive function Debette, et al., 2011  Brains of overweight and obese individuals appeared 8 and 16 years older, respectively Raji, et al., Brain Research Volume 1280, 14 July 2009, Pages 186–194

Figure 1 Comparison of studies of hippocampal volume in patients with cardiovascular disease Fotuhi, M. et al. (2012) Modifiable factors that alter the size of the hippocampus with ageing Nat. Rev. Neurol. doi: /nrneurol

Multiple Vascular Risk Factors: Worse Atrophy in the Brain Multiple Vascular Risk Factors No Vascular Risk Factors Hippocampus 19

Objectives  What is the difference between memory loss, MCI, and Alzheimer’s?  Why does the brain shrink with aging?  Can we reverse the effects of aging on the brain?  Can we grow the size of our brain?  Can we expand our cognitive performance and brain size? The Brain Fitness Program 20

Treating Vascular Risk Factors Slows Decline in Dementia Deschaintre et al., Neurology 73:674–80, 2009 Deschaintre, 20093:674–80,

Physical Activity and Mediterranean Diet, More Effective Together al., JAMA 302 (6):627–37, 2009 Scarmeas et al,

Objectives  What is the difference between memory loss, MCI, and Alzheimer’s?  Why does the brain shrink with aging?  Can we reverse the effects of aging on the brain?  Can we grow the size of our brain?  Can we expand our cognitive performance and brain size? The Brain Fitness Program 23

6 Steps to Grow Your Brain 1. Get Fit 2. Tease Your Memory 3. Eat Well &Take DHA 4. Sleep 5. Relax Your Mind 6. Start Early 24

1. Hippocampus Grows Bigger with Getting Fit Erikson, PNAS

Arch Gen Psychiatry, 2010 Hippocampus Grows Bigger with Exercise, Even After 3 Months After Before 26

More Exercise: More Brain Cells Van Praag, Trends in Neurosciences,

Draganski et al. J Neurosci 2006; 26:6314–7 2. Hippocampus Grows Bigger with Memorization Training 28

3. Hippocampus Grows Bigger with Eating Well & Taking DHA 29

More DHA-EPA: Bigger Hippocampus 30 Pottala J V et al. Neurology 2014;82:

Fotuhi et al., Nature Clinical Practice Neurology 5(3):140–52,

32 4. Hippocampus Grows Bigger with Treatment of Sleep Apnea Canesa, American Journal of Respiratory Medicine, 2011

5. Hippocampus Grows Bigger with Relaxing Your Mind Holzel, Psychiatric Research,

34 6. Hippocampus Grows Bigger When You Start Early

Figure 3 Pathways leading to hippocampal growth or atrophy Fotuhi, M. et al. (2012) Modifiable factors that alter the size of the hippocampus with ageing Nat. Rev. Neurol. doi: /nrneurol

Objectives  What is the difference between memory loss, MCI, and Alzheimer’s?  Why does the brain shrink with aging?  Can we reverse the effects of aging on the brain?  Can we grow the size of our Brain?  Can we expand our cognitive performance and brain size? The Brain Fitness Program 36

Brain Fitness Program  A multidisciplinary program devoted to: - Improving memory and brain performance - Enhancing long-term brain health - Reducing risk for dementia, Alzheimer’s disease and stroke in the future  Each patient receives a comprehensive baseline assessment followed by a personalized treatment plan  This program is based on latest research and has shown remarkable results 37

Comprehensive Diagnostics to Evaluate Brain Health Customized Treatment Program to Maximize Brain Performance NeurExpand’s Unique Integrative Approach 38

Neuro-feedback for Treatment of Depression 39

Immediate Memory Post Brain Fitness Program Follow-Up July 29, 2013 Letter FluencySustained AttentionProcessing Speed Delayed Memory 40

4/18/137/29/13 MoodAnxiety 4/18/137/29/134/18/137/29/13 Insomnia Cognitive InhibitionCognitive flexibilityInhibition & flexibility 41 Post Brain Fitness Program Follow-Up July 29, 2013

2.86 cm cm 3 42 MRI Results Before After

Objectives  What is the difference between memory loss, MCI, and Alzheimer’s?  Why does the brain shrink with aging?  Can we reverse the effects of aging on the brain?  Can we grow the size of our brain?  Can we expand our cognitive performance and brain size? The Brain Fitness Program 43

THANK YOU! 44

Baseline MRI… 45