Neuroanatomy and Neuroimaging: Application to Alzheimer’s disease diagnosis

1. Neuroanatomyand Neuroimaging: Application to Alzheimer’s disease diagnosis Megha Vasavada

2. Alzheimer’s disease • Most common form of dementia affecting 5.2 million Americans • Symptoms: problems with memory, thinking, and behavior • As the disease progresses the symptoms intensify • Disorientation • mood and behavior changes • deepening confusion about events, time and place • unfounded suspicions about family, friends and professional caregivers • more serious memory loss and behavior changes • difficulty speaking, swallowing and walking.

3. Central Nervous System • Controls both voluntary activities and autonomic functions • Integrates sensory information, emotions, thoughts, memory, and personality

4. Parietal Lobe Frontal Lobe • perception/ integration of somatosensory information (e.g. touch, pressure, temperature, and pain) • visuospatial processing • spatial attention • spatial mapping • number representation • 'higher' cognitive functions • attention • thought • voluntary movement • decision–making • language. Limbic Lobe Temporal Lobe • recognition • perception (hearing, • vision, smell) • understanding language • learning and memory Occipital Lobe • Vision Cerebellum • coordination of voluntary movement • motor–learning • balance and posture • reflex memory • timing • sequence learning • integration of sensory information Brainstem • maintaining homeostasis by controlling autonomic functions (blood pressure, breathing, digestion, heart rate, perspiration and temperature) • alertness • sleep • balance • startle response http://www.g2conline.org/2022

5. memory formation and storage • regulating emotion • processing smells Limbic Lobe

6. Frontal Lobe Parietal Lobe Occipital Lobe Temporal Lobe Cerebellum Brainstem Limbic Lobe

8. Magnetic Resonance Imaging

9. MRI: • Visualize structural changes • Track neuronal activation by studying blood flow (functional MRI)

10. Olfaction and Alzheimer’s • AD patients in the early stage have deficits in detection, recognition, and memory of an odor • AD patients have significantly reduced smell sensitivity • Areas involved in olfactory processing are the first areas affected by the classic pathology (Amyloid Beta plaques (Aβ) and neurofibrillary tangles (NFT))

11. Alzheimer’s Pathology • Amyloid Beta plaques • accumulation of Aβ in extracellular space. • Neurofibrillary tangles • hyperphosphorylated tau accumulation within neurons in the brain Diagnosis occurs here

12. Alzheimer’s Pathology

13. Overview • Basic neuroanatomy • Medial temporal lobe = start of AD patholgy • Olfactory areas are in the medial temporal lobe • Neuroimaging • MRI provides a tool to look at the anatomy and activation in humans Therefore, we will use MRI to study early changes in AD patients.

14. Hypothesis • Olfactory dysfunction will be present in our two patient groups • The volume of the primary olfactory cortex (POC) and hippocampus will be smaller in the two groups • The fMRI will show decreased activation in the POC and the hippocampus Overall- fMRI is more sensitive to earlier changes in MCI and AD patients

15. Subjects • AD, mild cognitively impaired (MCI), and normal controls were enrolled • MCI- considered the transitional stage from normal to AD (important group to study early diagnosis markers) 27 NC 21 MCI 15 AD

16. Methods • Smell test • University of Pennsylvania Smell Identification Test • MRI: • Anatomical scan • fMRI scan with an olfactory task

17. Smell Test- Results

18. POC and Hippocampus are smaller in MCI and AD Hippocampus POC

19. Activation is drastically decreased in MCI and AD CN MCI AD Hippocampus POC

20. Conclusion • UPSIT scores: • Smell function is affected in MCI and AD • Volume • hippocampus and POC in MCI and AD • Activation • in MCI and AD patients Activation changes are more drastic than behavioral or volumetric changes in the MCI group