1. Geriatric Psychiatry:A Review & UpdateMedical and Neurologic Aspects J. Wesson Ashford University of Kentucky VAMC, Lexington

2. Dementia Definition • Multiple Cognitive Deficits: • Memory dysfunction • At least one additional cognitive deficit • Cognitive Disturbances: • Sufficiently severe to cause impairment of occupational or social functioning and • Must represent a decline from a previous level of functioning Geriatric Psychiatry: A Review & Update

3. Differential Diagnosis: Top Ten 1. Alzheimer Disease (pure ~40%, + mixed~70%) 2. Vascular Disease, MID (5-20%) 3. Drugs, Depression, Delirium 4. Ethanol (5-15%) 5. Medical / Metabolic Systems 6. Endocrine (thyroid, diabetes), Ears, Eyes, Environ. 7. Neurologic (other primary degenerations, etc.) 8. Tumor, Toxin, Trauma 9. Infection, Idiopathic, Immunologic 10. Amnesia, Autoimmune, Apnea, AAMI Geriatric Psychiatry: A Review & Update

4. Diagnostic Criteria For Dementia Of The Alzheimer Type(DSM-IV, APA, 1994) • Multiple Cognitive Deficits 1. Memory Impairment 2. Other Cognitive Impairment B. Deficits Impair Social/Occupational • Course Shows Gradual Onset And Decline • Deficits Are Not Due to: 1. Other CNS Conditions 2. Substance Induced Conditions E. Do Not Occur Exclusively during Delirium F. Not Due to Another Psychiatric Disorder Geriatric Psychiatry: A Review & Update

5. Vascular Dementia(DSM-IV - APA, 1994) • Multiple Cogntive Impairments • Deficits Impair Social/Occupational • Focal Neurological Signs and Symptoms or Laboratory Evidence Indicating Cerebrovascular Disease Etiologically Related to the Deficits • Not Due to Delirium Geriatric Psychiatry: A Review & Update

6. Factors Associated with Multi-infarct Dementia • History of stroke (especially in Nursing Home) • Step-wise deterioration • Cardiovascular disease - HTD, ASCVD, & Atrial Fib • Depression (left anterior strokes), personality change • More gait problems than in AD • MRI evidence of T2 changes (?? Binswanger’s disease) • SPECT / PET show focal areas of dysfunction • Neuropsychological dysfunctions are patchy Geriatric Psychiatry: A Review & Update

7. Post-Cardiac Surgery • 53% post-surgical confusion at discharge (delirium) • 42% impaired 5 years later • May be related to anoxic brain injury, apnea • May be related to narcotic/other medication • May occur in those patients who would have developed dementia anyway (? genetic risk) • Cardio-vascular disease and stress may start Alzheimer pathology • Any surgery may have a similar effect related to peri-op or post-op anoxia or vascular stress Geriatric Psychiatry: A Review & Update Newman et al., 2001, NEJM

8. Drug Interactions • Anticholinergics: amitriptyline, atropine, benztropine, scopolamine, hyoscyamine, oxybutynin, diphenhydramine, chlorpheniramine, many anti-histaminics • May aggravate Alzheimer pathology • GABA agonists: benzodiazepines, barbiturates, ethanol, anti-convulsants • Beta-blockers: propranolol • Dopaminergics: l-dopa, alpha-methyl-dopa • Narcotics: may contribute to dementia Geriatric Psychiatry: A Review & Update

9. Depression • Onset: rapid • Precipitants: psycho-social (not organic) • Duration: less than 3 months to presentation • Mood: depressed, anxious • Behavior: decreased activity or agitation • Cognition: unimpaired or poor responses • Somatic symptoms: fatigue, lethargy, sleep, appetite disruption • Course: rapid resolution with treatment, but may precede Alzheimer’s disease Geriatric Psychiatry: A Review & Update

10. Delirium Definition • Disturbance of consciousness • i.e., reduced clarity of awareness of the environment with reduced ability to focus, sustain, or shift attention • Change in cognition (memory, orientation, language, perception) • Development over a short period (hours to days), tends to fluctuate • Evidence of medical etiology Geriatric Psychiatry: A Review & Update

11. Ethanol • Possibly Neuroprotective • May not kill neurons directly • Accidents, Head Injury • Dietary Deficiency • Thiamine – Wernicke-Korsakoff syndrome • Hepatic Encephalopathy • Withdrawal Damage (seizures) Delayed Alcohol Withdrawal • Watch for in hospitalized patients • Chronic Neurodegeneration • Cerebellum, gray matter nuclei Geriatric Psychiatry: A Review & Update

12. Medical / Endocrine • Thyroid dysfunction • Hypothyoidism – elevated TSH • Compensated hypothyroidism may have normal T4, FTI • Hyperthyroidism • Apathetic, with anorexia, fatigue, weight loss, increased T4 • Diabetes • Hypoglycemia (loss of recent memory since episode) • Hyperglycemia • Hypercalcemia • Nephropathy, Uremia • Hepatic dysfunction (Wilson’s disease) • Vitamin Deficiency (B12, thiamine, niacin) • Pernicious anemia – B12 deficiency, ?homocysteine Geriatric Psychiatry: A Review & Update

13. Eyes, Ears, Environment • Must consider sensory deficits might contribute to the appearance of the patient being demented • Central Auditory Processing Deficits (CAPD) • Hearing problems are socially isolating • Visual problems are difficult to accommodate by a demented patient, ?To do cataract op? • Environmental stress factors can predispose to a variety of conditions • Nutritional deficiencies (tea & toast syndrome) Geriatric Psychiatry: A Review & Update

14. Neurological Conditions • Primary Neurodegenerative Disease • Diffuse Lewy Body Dementia (? 7 - 50%) • Fronto-temporal dementia (tau gene) • Focal cortical atrophy • Primary progressive aphasia (many causes) • Unilateral atrophy, hypofunction on EEG, SPECT, PET • Normal pressure hydrocephalus • Dementia with gait impairment, incontinence • Suggested on CT, MRI; need tap, ventriculography • Other Neurologic Conditions Geriatric Psychiatry: A Review & Update

15. Tumor • Toxins • Trauma Geriatric Psychiatry: A Review & Update

16. Infectious Conditions Affecting the Brain • HIV • Neurosyphilis • Viral encephalitis (herpes) • Bacterial meningitis • Fungal (cryptococcus) • Prion (Creutzfeldt-Jakob disease); (mad cow disease) Geriatric Psychiatry: A Review & Update

17. Amnesic Disorders • Amnesia • Dissociative: localized, selective, generalized • Organic - damage to CA1 of hippocampus • thiamine deficiency (WKE), hypoglycemia, hypoxia • Epileptic events • Partial complex seizures • Specific brain diseases • Transient global amnesia • Multiple sclerosis Geriatric Psychiatry: A Review & Update

18. Age-Associated Memory ImpairmentvsMild Cognitive Impairment • Memory declines with age • Age - related memory decline corresponds with atrophy of the hippocampus • Older individuals remember more complex items and relationships • Older individuals are slower to respond • Memory problems predispose to development of Alzheimer’s disease Geriatric Psychiatry: A Review & Update

19. Advances in Alzheimer’s Disease Uncovering etiology Understanding pathophysiology Better screening tools Improved diagnosis Developing interventions

20. Etiology • Age - therefore - design and stress • Genetics (amyloid related) • Relation to vascular factors, cholesterol, BP • Education (? design vs protection) • Environment - diet, exercise, smoking Geriatric Psychiatry: A Review & Update

21. Neuropathology of AD • Senile plaques • Neurofibrillary tangles • Neurotransmitter losses • Inflammatory responses New Neuropath Mechanisms • Amyloid PreProtein (APP - ch21) • Tau phosphorylation (relation to dementia) Geriatric Psychiatry: A Review & Update

22. Biopsychosocial Systems Affected by AD(all related to neuroplasticity) • Social Systems • Basic ADLs - Late • Psychological Systems • Primary Loss Of Memory • Later Loss Of Learned Skills • Neuronal Memory Systems • Cortical Glutamatergic Storage • Subcortical (acetylcholine, norepi, serotonin) • Cellular Plastic Processes • APP metabolism – early, broad cortical distribution • TAU hyperphosphorylation – late, focal effect, dementia related Geriatric Psychiatry: A Review & Update

23. Why Diagnose AD Early? • Safety (driving, compliance, cooking, etc.) • Family stress and misunderstanding (blame, denial) • Early education of caregivers of how to handle patient (choices, getting started) • Advance planning while patient is competent (will, proxy, power of attorney, advance directives) • Patient’s and Family’s right to know • Specific treatments now available, may delay nursing home placement longer if started earlier Geriatric Psychiatry: A Review & Update

24. Need for Better Screening and Assessment Tools • Genetic vulnerability testing • Early recognition (10 warning signs) • Screening tools (6th vital sign in elderly) • Positive diagnostic tests • CSF – tau levels elevated, amyloid levels low • Brain scan – PET – DDNP, Congo-red derivatives • Dementia severity assessments • Tracking progression rate, prediction of change Geriatric Psychiatry: A Review & Update

25. Alzheimer Warning SignsTop TenAlzheimer Association 1. Recent memory loss affecting job 2. Difficulty performing familiar tasks 3. Problems with language 4. Disorientation to time or place 5. Poor or decreased judgment 6. Problems with abstract thinking 7. Misplacing things 8. Changes in mood or behavior 9. Changes in personality 10. Loss of initiative Geriatric Psychiatry: A Review & Update

26. Assessment • History Of The Development Of The Dementia • Physical Examination • Neurological Examination Geriatric Psychiatry: A Review & Update

27. Neurological Exam • Cranial Nerves • Sensory Deficits • Motor • Deep tendon • Pathological Geriatric Psychiatry: A Review & Update

28. Geriatric Psychiatry: A Review & Update

29. Mini-Mental State Exam items Geriatric Psychiatry: A Review & Update

30. Laboratory Tests ROUTINE • Routine – Blood tests & Urinalysis • EKG • Chest X-Ray • Anatomical Brain Scan – CT (cheapest), MRI SPECIAL • Functional Brain Imaging (SPECT, PET) • EEG, Evoked Potentials (P300) • Reaction Times • CSF Analysis - Routine Studies • Heavy Metal Screen (24 hr urine) • Genotyping Geriatric Psychiatry: A Review & Update

31. Justification for Brain Scan in Dementia Diagnosis • Differential Diagnosis: Tumor, Stroke, Subdural Hematoma, Normal Pressure Hydrocephalus, Encephalomalacia • Confirmation of atrophy pattern • Estimation of severity of brain atrophy • MRI shows T2 white matter changes • Periventricular, basal ganglia, focal vs confluent • These may indicate vascular pathology • SPECT, PET - estimation of regions of physiologic dysfunction, areas of infarction • Helps family to visualize problem Geriatric Psychiatry: A Review & Update

32. Geriatric Psychiatry: A Review & Update

33. Geriatric Psychiatry: A Review & Update

34. Geriatric Psychiatry: A Review & Update

35. Ashford et al, 2000 Geriatric Psychiatry: A Review & Update

36. INTERVENTIONS • Only successful intervention – • Cholinesterase Inhibition (1st double blind study - Ashford et al., 1981) • Available Interventions – • Not yet proven or unconvincing effects • Promising Interventions Geriatric Psychiatry: A Review & Update

37. Other Medical Conditions • Chronic pain syndrome • Medical consultation-liaison Other Neurological Conditions • Parkinson’s disease • Guillan Barre syndrome • Huntington’s disease • Seizure disorders – partial complex seizures Geriatric Psychiatry: A Review & Update

38. Parkinson’s Disease • Increases steadily after 50 years of age • Pathophysiology • Concomitant conditions • Parkinson signs • Symptomatic treatment Geriatric Psychiatry: A Review & Update

39. Electroencephalography • Seizure disorders • Sensitivity – 50% (90% after 3 recordings) • Episodic behavior problems • Possible partial seizure disorder • Generalized slowing • Primary neurodegeneration • Temporal slow waves may be “normal” • Focal slowing (stroke, focal cortical disease) • Specific neurologic syndromes • Creutzfeldt-Jakob disease • Sleep disorders • In sleep studies: used to define stages Geriatric Psychiatry: A Review & Update

40. Behavioral Problems In Dementia Patients • Mood Disorders – depression – early in AD • Psychotic Disorders • Particularly paranoia, e.g, people stealing things • Agitation • Meal Time Behaviors • Sleep Disorders Geriatric Psychiatry: A Review & Update

41. Neuropsychiatric Treatments • First treat medical problems • Second environmental interventions • Third neuropsychiatric medications Geriatric Psychiatry: A Review & Update

42. Sleep Disorders • Primary sleep problems • Breathing-related sleep disorders • Narcolepsy / primary hypersomnia • Circadian rhythm disorders • Parasomnias • Secondary sleep problems • Due to a psychiatric condition: depression, psychosis • Due to a medical condition: arthritis, parkinson’s • Substance induced disorders • Fragmented circadian rhythms, sleep in AD Geriatric Psychiatry: A Review & Update

43. Insomnia 15% of patients in sleep labs have sleep disturbance not associated with extrinsic factors or other conditions • Periodic limb movement, restless leg syndrome • Sinemet or anti-convulsants • PTSD, nightmares (trazodone, prazosin) • Jet lag (? melatonin) • Drugs: caffeine, nicotine, • Sleeping pill rebound Geriatric Psychiatry: A Review & Update