DEMENTIA

1. DEMENTIA

2. Marilou G. Tablang-Jimenez, M.D., DFAPA Chair, MedStar Montgomery Medical Center, Department of Psychiatry Asst Professor, MedStar Georgetown University Medical Director, Montgomery County Crisis Center Medical Director, MGTJ, PC Group Practice Honorary Clinical Instructor, Walden University

3. Disclaimer Speaker’s Bureau Pfizer Eli Lilly Janssen Sunovion

4. “Fun” facts about Dementia before we start • AD is 6th Leading cause of death in the US; 5th for those 65 and older • Women make up a larger share (2/3) of Alzheimer’s (AD) patients than men • Lifetime risk is 20% for women and 10% for men at age 45 • AA and Hispanics are morel likely to have AD as likely as Whites. LOWEST FOR ASIAN-AMERICANS! The Japanese have the lowest. • Negative socio-economic characteristics maybe increase for those groups

6. More “fun” facts • In the US, 15.8% of age 60 and older have MCI • The oldest member of the Baby Boom generation (1946-1964) just turned 72 in 2018 • Decline in the age-specific risk of AD and other dementias in the past 25 years • BUT a dramatic increase is expected in the TOTAL NUMBER of cases • A worldwide trend showing an increase in OBESITY and DIABETES can potentially reverse the declining trend • In low- and middle-income countries, such as the Philippines, there is no evidence that the risk for AD and other dementias has been declining

7. Last “fun” facts • $232 Billion expense in 2017 and $277 Billion in2018 • Costs extend to family caregivers’ increased risk for emotional distress and negative mental and physical health outcomes • With the identification of biomarkers in recent years, our understanding of AD has changed

8. NEURO-COGNITIVE DISORDERS (NCD)Acquired and represents decline from previous level of functioning Mild NCD aka Mild Cognitive Impairment (MCI or MCD) Moderate NCD aka DEMENTIA Significant decline Substantial impairment 2 or more cognitive domains Attention, Learning/Executive Function, Memory, Language, Emotion, Visuospatial Function/Motor & Action Interferes with independence +/- Behavioral Disturbance Mild, Moderate or Severe • Moderate decline • Modest impairment • Does not interfere with independence • +/- Behavioral Disturbance

9. Possible Reversible Causes of NCD • Depression • Delirium • Substance or Medication Induced > Alcohol > Medication Mismanagement > Anticholinergics > Benzodiazepines • BENADRYL, Parkinson’s Rx, Antipsychotics, Ditropan > Ativan, Xanax, Clonazepam, Vaiium > Statins > Medication Mismanagement • Hypothyroidism, Vit B12 Deficiency, Neuro-syphillis • Normal Pressure Hydrocephalus (NPH), Subdural Hematoma, Brain Tumor • Sensory Impairment, especially hearing

10. DEPRESSION • Associated with an increased risk of Alzheimer’s Disease • Depression and other neuropsychiatric symptoms often emerge during the preclinical phase of AD – a period marked by the accumulation of deposits of fibrillar amyloid and pathological tau • Cognitively normal older adults with worsening anxiety had higher levels of amyloid beta, a brain protein implicated in AD

11. LINK BETWEEN DEPRESSION AND DEMENTIA • Those with MCI were 2.6 times more likely to have a history of depression • Those with AD were 3.77 times more likely to have had depression

14. DEPRESSION WITH ANXIETY • When compared with other symptoms of depression, ANXIETY SYMPTOMS increased over time in those with higher amyloid beta levels in the brain • Anxiety may be a manifestation of the disease process BUT it may also be a DISEASE-POTENTIATING FACTOR

15. ANTI-DEPRESSANT MEDICATION • The antidepressant SSRI Citalopram and Sertraline decrease amyloid-Beta generation and plaque load. • SSRI was associated with delayed dementia onset and increased longevity in patients with Down Syndrome, who have a high risk of AD

16. ANTI-DEPRESSANT MEDICATIONS • Long-term treatment of depression (more than 4 years, even after the depressive symptoms have resolved) with SSRI of those with MCI was associated with a delay of approximately 3 years in progression of Alzheimer’s • SSRI cannot stop the AD pathology • Non-SSRI antidepressants were associated with a higher risk of progression from MCI to AD

18. DELIRIUM (vs Dementia) • Disturbance in ATTENTION or AWARENESS + another deficit • Develops over short period of time and tends to fluctuate • Direct physiological consequence of something else • Hyperactive (easy to Dx) or hypoactive (easy to miss) types • Can be reversible – SIGNIFICANT CAUSE OF MORBIDITY AND MORTALITY during acute hospital admission

19. SENSORY IMPAIRMENT- HEARING LOSS • Age-related hearing loss linked to impaired performance across cognitive domains and increased risk for Dementia diagnosis • Underlying PSYCHOSOCIAL MECHANISM of diminished hearing leading to increased risk for depression

20. SENSORY IMPAIRMENT – HEARING LOSS • Underlying NEUROBIOLOGICAL MECHANISM of diminished hearing leading to increased risk for depression • DECREASE COGNITIVE PERFORMANCE and INCREASE DEPRESSION RISK by • Reducing cognitive reserve • Increasing executive dysfunction • Disrupting normative emotion reactivity and regulation

21. What does it mean to have “Dementia?” • COGNITIVE IMPAIRMENT • Learning and Memory • Executive Function • Language Skills • ETC • FUNCTIONAL IMPAIRMENT • Instrumental Activities of Daily Living (IADLs) • Activities of Daily Living (ADL)

22. Diagnosis of Dementia • Is cognitive impairment present • Is there anything I can fix? • Time will tell – Is this dementia? If so, what is the etiology?

24. Basic Work-Up for Dementia • Clinical Evaluation • Hx – Cognitive & Functional (collaborative informant) • Cognitive Testing – MMSE or Montreal Cognitive Assessment • Neurological Exam – Focal S/Sx, Parkinsonism • Review of Current Rx and Substance Use • Laboratory Studies (TSH, B12, Syphillis) • Brain Imaging – CT Scan or MRI, possibly PET Scan • Others as clinically indicated – Lyme’s, EEG

25. Dementia in the Elderly • Alzheimer’s Disease 65% • Frontotemporal Lobar Degeneration 10% • Vascular Dementia 10% • Lewy Body Dementia 5% • Other/Mixed 10% • Substance/Medication Use, HIV Infection, Prior Disease, Parkinson’s Disease, Huntington’s Disease, Other Medical Conditions • These numbers vary widely

26. ALZHEIMER’S DISEASE • Primary deficit is the decline in memory and learning – short-term, episodic • Executive Dysfunction can occur early on • Insidious onset and gradually progressive decline • Cause is multifactorial; <5% is genetic; plaques and tangles in the brain • Greatest risk factor is advancing age; also family history and genetics (ApoE3 allele) • Neurological exam unremarkable in mild to moderate stages • AD is a LIFE-LIMITING ILLNESS that lasts 8-12 years on average

27. ALZHEIMER’S DISEASE • Cognitive Impairment • Amnesia (partial or total loss of memory) • Aphasia (loss of ability to understand or express speech) • Apraxia (inability to perform purposeful actions) • Agnosia (inability to interpret sensations and to recognize things) • Executive Dysfunction • No evidence of neurological disease, metabolic etiology, substance-induced, or delirium • Significant functional impairment in IADLs or ADLs

28. Early Stage of AD - Mild • Short-term memory is poor • Expressive language and naming are affected • Executive function is impaired • Trouble with IADLs (higher level activities) • Some activities are taken over by others • Need gentle reminders and supervision • Close family and friends can notice

29. What does early AD typically look like? COGNITIVELY FUNCTIONALLY Forget conversations Forget dates, miss appointments Misplace items frequently Trouble with finances Get lost while driving • Short-term memory loss • Word-finding difficulties • Trouble with reasoning • Becoming lost or disoriented

30. Stages of AD – Moderate (Middle) • Long-term memory becomes affected • Decision-making is harder (limit to 2 choices) • Speech comprehension is difficult • “Praxis” (doing things) is more impaired • ADLs are affected (personal care) • Need cuing, set-up and assistance • Incontinence develops in the 2nd half • Gait disturbance with falls • Becomes more obvious to others

31. Stages of AD – Severe (Late) • All cognitive domains are affected • “Gnosis” (recognizing people) is affected • Very basic information is lost, including one’s name • Become unable to walk, talk, feed oneself • Fully dependent on others for care • Neurological changes and abnormalities • Swallowing becomes affected

32. FRONTO-TEMPORAL DEMENTIA (FTD) • Age of onset: 40-65 • Behavioral variant – Pick’s Disease (Frontal Lobe) • Language variant – Primary Progressive Aphasia or Semantic Dementia (Temporal Lobe) • Relative sparing of learning, memory, and perceptual motor function • Several different gene mutations have been identified • Most cases without family history • Can be associated with Motor Neuron Disease (ALS)

33. VASCULAR DEMENTIA • Presence of sufficient cerebrovascular disease • Prominent deficits in complex attention and frontal executive function • Symptoms vary • Thinking is more affected than memory • Temporally related to cerebrovascular events • Can occur suddenly (pot-stroke) or step-wise (series of strokes) • Exam may show focal deficits and gait disturbance • Risk Factors: Age, Hx of MI, CVA, TIA, Atherosclerosis, Hyperlipidemia, HTN, DM, Smoking, A-fib

34. DEMENTIA WITH LEWY BODIES • Prominent visual hallucinations • Fluctuation in attention and awareness – mimics delirium • Subsequent Parkinsonism (slowed movement, rigidity, imbalance with falls) • REM Sleep behavior disorder and neuroleptic sensitivity are common • Risk factors: Age, Male, family history of DLB

35. DEMENTIA DUE TO TRAUMATIC BRAIN INJURYTBI increases risk of developing AD, PD, or Dementia Pugilistica (Boxers) • External force to the head or body (mild, moderate, severe) • Causes are falls, motor vehicle collisions, violence, sports injuries, blasts • LOC, post-traumatic amnesia, disorientation & confusion, neurological signs • NCD presents IMMEDIATELY after and persists • Affects attention, speed of processing, memory, executive function

36. PARKINSON’S DISEASE WITH DEMENTIA • Must have an established diagnosis of PD • Cognitive dysfunction is very common • Dementia occurs in 20-40% of PD late in the disease (10-15 years) • Slowed thinking, impaired attention/concentration, executive dysfunction • Risk Factors: Age, More severe motor symptoms

37. PLAN OF CARE FOR DEMENTIA#1 Address Safety Issues • DRIVING!!! • The ability to drive safely is lost at this stage • Guns • Medications • Finances • Cooking • Wandering • Falls

38. PLAN OF CARE FOR DEMENTIA#2 General Management • Manage neuropsychiatric comorbidities • Control vascular risk factors • Discontinue offending medications • Increase hydration • Physical exercise • Cognitive stimulation • Social engagement • Memory aids (pillbox, calendar, etc.) • Advance planning = Home Care Assistance

39. PLAN OF CARE FOR DEMENTIA#3 Dementia Specific Medications • Symptomatic Treatment – not disease modifying • Modest and temporary response • Cholinesterase inhibitors (ChEi) • Donepezil, Rivastigmine, Galantamine – no significant difference between them • For mild, moderate or severe stages of AD • S/E: N/V/D and weight loss (less with patch), bradycardia, syncope, falls, urinary frequency

40. PLAN OF CARE FOR DEMENTIA#3 Dementia Specific Medications • NMDA Receptor Antagonist • Memantine • For moderate to severe AD • Comes in XR (24 hour capsule can be sprinkled) • Reduce the dose with severe renal impairment • S/E: Dizziness,irritability • Evidence for combination therapy • Namzaric

41. POTENTIAL PHARMACOLOGICAL TREATMENTS • Targeting amyloid beta • Breaking up the amyloid beta by binding them to prevent amyloid aggregation • Blocking the enzyme Beta-secretase (BACE) that produces amyloid beta • Vaccination to induce the immune system to generate the antibodies against the amyloid beta • Targeting the Tau • Inhibition of the Receptor for Advanced Glycation End Products (RAGE) that may interfere with inflammation and amyloid transportation into the brain

42. POTENTIAL PHARMACOLOGICAL TREATMENTS • A molecule that hits several types of Serotonin, Dopamine and Glutamate receptors is being developed for the treatment of agitation in AD and other dementia, as well as Schizophrenia • Other strategies being research to treat AD include fixing dysfunctions in • Mitochondria (produce energy for cells) • Endocytosis (transportation of molecules in and out of cells) • Autophagy (self-cleaning process inside cells)

43. NEW TOOLS BEING DEVELOPED • Sharpen the brain images • Cutting-edge biomarkers (PET Imaging or molecules in CSF) to help diagnose AD early and measure disease progress with unprecedented accuracy • Refinement in genetic analysis may clarify different pathological processes in subgroups of AD and lead to more targeted treatment

44. BEHAVIORAL AND PSYCHOLOGICL SYMPTOMS OF DEMENTIA (BPSD) • Behavioral symptoms: loud vocalization, restlessness, agitation, wandering, physical aggression (not the norm) • Psychological symptoms: anxiety, depressive mood, hallucinations, delusions • Usually in the Middle to Late stages • Apathy is prevalent throughout • Sleep disorders are common (Circadian Rhythm Disturbance) • Can negatively affect the quality of life

45. BPSD NON-PHARM MANAGEMENT • Rule-out medical causes • Pain, constipation, delirium from illness • Establish other root causes • Boredom, routine change, personal needs, fatigue, environmental factors, mismatch of task & ability, arguing • Use behavioral interventions • Individualized approaches directed toward understanding, preventing, relieving, and/or accommodating distress or loss of abilities

46. BPSD PHARMACOLOGIC MANAGEMENTThere is no FDA-approved treatment for BPSD • Choose a target behavior, for example • Depression or anxiety – SSRI • Psychosis or fearfulness – Antipsychotic • Sleep disturbance – Sedating antidepressants • Situation agitation/aggression – Low-dose BZD • Persistent aggression – Antipsychotic or Mood Stabilizer • Consider the frequency & severity • RULE OF THUMB: START WITH ½ OF THE SMALLEST PILL

47. Key Principles for Antipsychotic Use • Ideally, for dangerousness, psychosis or mania • Antipsychotics only when non-pharm has failed • Document the reason & rationale for starting • Time-limited use with gradual dose reductions • Inappropriate for vocalizations and wandering

48. BPSD PHARMACOLOGIC MANAGEMENT • Small improvements in certain symptoms with Antipsychotics • Other evidence in favor of Risperidone • Choice is largely based on side-effects profile • Citalopram may be as effective as Risperidone • Try an SSRI before an antipsychotic, if appropriate

49. PREVENTION & INTERVENTION • Conceptualizing cognitive impairment as a GERIATRIC SYNDROME rather than a set of clinical or preclinical diagnoses • Evaluation and management of cognitive decline should include • Assessment ad treatment of depression • Screening for hearing impairment • Appropriate referral • Other components to be incorporated should address cerebrovascular risk factors, especially white matter disease, such as management of • HTN • DM • A-fib

50. PREVENTION & INTERVENTION • Active treatment of midlife obesity • Exercise • Dietary modifications • Mediterranean diet with low proinflammatory potential • Smoking cessation • Assessment of alcohol intake, with MODERATION being the focus in midlife and CESSATION being important if cognitive impairment is present in later life • Social engagement prevents loneliness and depression • Participation in cognitive stimulating leisure activities is associated with higher cognitive performance • Attending to mobility issues as impairments have been shown to worsen outcomes for a variety of disorders and are associated with cognitive decline