Exploring Advances in the Early Diagnosis and Treatment of Alzheimer Disease webinar

i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.

In this slide deck, discover new insights into early diagnosis, emerging treatment modalities, and supportive care services for Alzheimer disease. An expert faculty member will discuss biological and clinical distinctions between mild cognitive impairment, dementia, and Alzheimer disease; methods for timely diagnosis; clinical trial data on novel monoclonal antibody therapies; prevention and management of side effects associated with monoclonal antibody therapies, including ARIA, and interdisciplinary support services for improving quality of life.

STATEMENT OF NEED

Alzheimer disease, the most common form of dementia among older adults, is a slowly progressive neurogenerative disease that affects approximately 6 million Americans aged 65 and older (Rajan et al, 2021). Symptoms of Alzheimer disease include memory loss, confusion, impulsive behavior, difficulty with language, mood and personality changes, hallucinations, and increased anxiety or aggression, with severe symptoms such as physical decline, difficulty swallowing, and inability to communicate developing as the disease progresses into its final stages (NIA, 2023). While new therapeutic agents have recently emerged to slow the progression of Alzheimer disease by targeting its underlying causes, the disease remains incurable, and the demands of day-to-day care place significant strain on both patients and their families and caregivers. Therefore, it is critical that clinicians remain up to date on early diagnosis, emerging treatment modalities, and supportive care services in order to provide optimal care for their patients. In this live webinar chaired by Nathaniel Chin, MD, Associate Professor of Medicine in the Division of Geriatrics and Gerontology at the University of Wisconsin-Madison, speakers will explore advances in the diagnosis and treatment of Alzheimer disease.

TARGET AUDIENCE

Geriatricians, neurologists, primary care physicians, psychiatrists, psychogeriatricians, nurse practitioners, physician assistants, nurses, and other health care professionals (HCPs) involved in the treatment of patients with Alzheimer disease (AD).

LEARNING OBJECTIVES

Upon completion of this activity, participants should be able to:

Utilize diagnostic methods that enable the timely identification of early Alzheimer disease (AD)
Evaluate the clinical utility of novel and emerging DMTs for the treatment of individual patients with early AD
Apply strategies to enhance interdisciplinary care for patients with early AD

1. Exploring Advances in the Early Diagnosis and Treatment of Alzheimer Disease Nathaniel Chin, MD Associate Professor of Medicine, Division of Geriatrics and Gerontology Medical Director, Wisconsin Registry for Alzheimer’s Prevention Study University of Wisconsin-Madison

2. Disclosures A dvisory board/panel: NewAmsterdam Pharma i3 Health has mitigated all relevant financial relationships

3. Learning Objectives Utilize diagnostic methods that enable the timely identification of early Alzheimer disease (AD) Evaluate the clinical utility of novel and emerging disease-modifying therapies (DMTs) for the treatment of individual patients with early AD Apply strategies to enhance interdisciplinary care for patients with early AD

4. Alzheimer’s Disease Jack et al, 2018; Silbert, 2007; Neuroscience News, 2012. Alzheimer’s disease is not the same as dementia Alzheimer’s disease is defined biologically as the presence of elevated amyloid proteins and tau proteins in the brain As a disease process, it is the most common cause of neurodegeneration leading to dementia Cerebral cortex Hippocampus Entorhinal cortex Extreme shrinkage of cerebral cortex Severely enlarged ventricles Extreme shrinkage of hippocampus

5. Clinical Syndromes of Cognitive Impairment Albert et al, 2011; Jack et al, 2018. Mild Cognitive Impairment (MCI) Cognitive symptom(s) that: Raise concern to patient, knowledgeable informant, or health care provider Represent a decline from baseline Impairment in ≥1 cognitive domains Preservation of independence in functional abilities Dementia Cognitive symptom(s) that: Interfere with ability to function at work or usual activities Represent a decline from previous level Are not explained by delirium or major psychiatric disorder Cognitive impairment is detected and diagnosed by: History from patient and knowledgeable informant Objective cognitive assessment “Bedside” mental status examination or neuropsychological assessment Neuropsychological assessment should be done if history and beside exam do not lead to a confident diagnosis Affect ≥2 thinking abilities on cognitive testing Dementia due to AD Gradual onset over months to years Worsening of cognition over time Usually, memory-complaint initially

6. Alzheimer’s Disease: Prevalence Alzheimer’s Association, 2023; Alzheimer’s Association, 2022; Rajan et al, 2021; Peterson et al, 2018. Approximately 5 Million Americans Have MCI Due To AD Age Prevalence of MCI 60-64 6.7% 65-69 8.4% 70-74 10.1% 75-79 14.8% 80-84 25.2% 30%-50% of people with MCI due to AD will progress to Alzheimer’s dementia over a 5-10–year period Number and Ages of People 65 or Older with Alzheimer’s Dementia, 2023

7. Alzheimer’s Disease Impacts Communities Differently ADRD = Alzheimer’s disease and related dementias. Alzheimer’s Association, 2023; Barnes, 2022; Trojanczyk et al, 2019. Incidence of AD is almost 2x higher in older African American individuals Risk of AD in Hispanic/Latino individuals is 1.5x more Native Americans are at higher risk for AD and dementia than White or Asian Americans; 1 in 3 Native American elders will develop ADRD Estimated Lifetime Risk for AD Age Risk in men Risk in women 45 10.3% 19.5% 65 11.6% 21.1%

8. Alzheimer’s Disease Cases Will Continue to Increase Alzheimer’s Association, 2023; Rajan et al, 2021. Projected Number of People 65 or Older (Total and by Age) in the US Population with Alzheimer’s Dementia, 2020 to 2060

9. Alzheimer’s Disease: Economic Impact Distribution of Aggregate Costs of Care by Payment Source for Americans Age 65 or Older with Alzheimer’s or Other Dementias, 2023 Data are in 2023 dollars Created from data from the Lewin Model. Other payment sources include private insurance, health maintenance organizations, and uncompensated care. The sum of individual dollar amounts does not equal the total coast due to rounding. Alzheimer’s Association, 2023.

10. Care Starts With a Diagnosis Alzheimer’s Association, 2023. 40% of Americans would talk to their doctor right away if experiencing early memory or cognitive loss 70% of Americans would want to know early if they have Alzheimer’s disease if it could allow for earlier treatment Yet… 54% of Americans who experienced cognitive symptoms did not consult with a health care professional 41% who had cognitive symptoms interfering with daily function did not talk with a provider 97% of primary care physicians report waiting for patients to make them aware of symptoms or request an assessment

11. Reasons for a Delay in Diagnosis AA = Alzheimer’s Association; PCP = primary care provider. Alzheimer’s Association, 2022. 18% of Americans are familiar with MCI (AA survey) 98% of PCPs report it is important to diagnose MCI 35% of PCPs reported being not fully comfortable diagnosing MCI and 51% of PCPs not fully comfortable diagnosing MCI due to AD Top reasons for discomfort: differentiating normal aging from MCI, difficulty interpreting daily functioning, lack of specialists for diagnostic testing 38% of PCPs reported specialists are better equipped to assess and diagnose patients with cognitive impairment, while 43% felt specialists are better equipped to discuss cognitive assessments 99% of PCPs refer patients to specialists when they detect cognitive impairment

12. Benefits of an Early Diagnosis: Patient/Family Reiss et al, 2022. Can help explain symptoms, personality changes, behavioral changes Provides an answer to patient and family suspicions/concerns Earlier interventions Access to right services and support; medications Maintain a good quality of life Patients can participate in their care and discuss future care options Patients can participate in their own legal and financial decisions Helps patients and family prepare for future functional change and potential safety issues Allows family members and friends to develop new roles of support Gives time for families and care partners to become more educated

13. Benefits of an Early Diagnosis: Provider Reiss et al, 2022. Address brain health and mental health Address chronic diseases with a new lens Make earlier referrals Monitor for functional changes (ie, driving) and safety issues Connect patient/family to community organizations Address advanced directives and future care planning Refer to clinical research

14. Diagnostic Workup McCollum & Karlawish, 2020; Geerlings et al, 1999; Jessen et al, 2010; Barnes et al, 2006; Arvanitakis et al, 2018. Assess risk factors for cognitive impairment Age, family history of dementia, chronic medical conditions Ask about concerns for memory or thinking changes Examples Do you feel like your memory is becoming worse? How often do you have trouble remembering things? (scale 1-5) Compared with 10 years ago, how would you rate your memory? (scale 1-5) If possible, talk with a knowledgeable informant Family, friend, someone who knows person well enough to potentially have concerns

15. Cognitive Screening Janssen et al, 2017. Not the same as cognitive testing or neuropsychological testing Not diagnostic testing Some exceptions Explain the test and purpose of testing before administering Set expectations and allow the patient to mentally prepare

16. Cognitive Screening (cont.) Reiss et al, 2022. Considerations Well-trained staff should administer test Stick to the guidelines of the instrument Results should be discussed with patient/family Avoid using instrument cutoffs for diagnosis Talking points prior to testing Performance testing is an objective measurement to potentially identify cognitive changes beyond normal aging May not reflect what a person feels or others witness Artificial process (quiet, isolated room, specific tasks)

17. Cognitive Screening Instruments Reiss et al, 2022. Mini-Mental State Examination (MMSE) Saint Louis University Mental Status Exam (SLUMS) Montreal Cognitive Assessment (MoCA) Mini-cog Memory Impairment Screen (MIS) Brief Alzheimer’s Screening Test (BAS) General Practitioner assessment of Cognition (GPCOG) AD8 Informant Interview (not a test)

18. How To Diagnose Cognitive Impairment? Reiss et al, 2022. Cognitive and functional history Cognitive symptoms Functional changes, if any Cognitive screening Separate visit, if needed Does not provide definitive answers Evaluate for reversible causes, including delirium and mental health History Labs Brain imaging Physical exam Labs and head imaging

19. Cognitive History Reiss et al, 2022. Symptom identified Patient, family, provider, routine screening Patient and collateral historian Cognition Onset, initiating event?, course Specific symptoms and examples Medical changes during this time Including head injuries, acute illnesses, surgeries Mood, personality, behavior Sleep, hearing Review medical history, medications, family history, substance history

20. Functional History BADL = basic activities of daily living. Chudoba et al, 2020; de Ruijter et al, 2020. Collateral historian is key Patient perspective is important, but insight changes with disease progression Inquire about specific safety concerns or events/issues noticed by family Check list approach, reviewing IADLs and then BADLs Semi-structured interview

21. What Are the Common Functional Abilities To Assess? Slide courtesy of Nathaniel Chin, MD. Making and keeping appointments Managing medications Managing finances Driving Meal preparation and cooking Household chores Use of technology Maintaining hobbies Basic activities of daily living Dressing Bathing Toileting Transferring Walking Eating

22. Functional Impairment IADL = instrumental activities of daily living; ER = emergency room. Slide courtesy of Nathaniel Chin, MD. Compare current abilities with baseline Start with IADLs Most complex are managing finances, medications, appointments Collateral historian is key Ideally someone who lives with the patient (spouse, child) Patient endorsement is more confirmation than identification Compensatory strategies are okay and expected in MCI Rare, infrequent mistakes may not be impairments Objective impairments are easier to identify Missed payments, ER visits due to medication non-adherence Impairments must be due to cognition, not due to mood/physical limitations

23. Look for Reversible Causes & Talk To Brain Health HIV = human immunodeficiency virus; UTI = urinary tract infection; NPH = normal pressure hydrocephalus. Slide courtesy of Nathaniel Chin, MD. Medication reconciliation Mood assessment Evaluate alcohol intake or other substances Evaluation sleep and rule out sleep apnea Kidney, liver, or thyroid issues Hearing or vision issues Chronic infections Syphilis, Lyme disease, HIV, COVID-19 Acute infections UTI, cellulitis, pneumonia, viral colds Brain imaging for subdural hematoma or NPH

24. Potential Tools in the Evaluation Process GDS = Geriatric Depression Scale; PHQ = Patient Health Questionnaire; GAD = Generalized Anxiety Disorder; GAS = Geriatric Anxiety Scale; STOP-BANG = snoring/tiredness/observed apnea/pressure/body mass index/age/neck circumference/gender; IQCODE = Informant Questionnaire on Cognitive Decline in the Elderly; ADLs = activities of daily living; FAQ = Functional Activities Questionnaire; QDRS = Quick Dementia Rating System; DSRS = Dementia Severity Rating Scale; FAST = Functional Assessment Rating Scale. Slide courtesy of Nathaniel Chin, MD. Patient Cognition MoCA or MMSE or SLUMS Mental health GDS or PHQ-9 GAD-7 or GAS Sleep apnea STOP-BANG Informant Cognitive changes Short IQCODE or AD8 Function Lawton IADLs/Katz ADLs FAQ Staging QDRS or DSRS FAST

25. Physical Exam Slide courtesy of Nathaniel Chin, MD. Neurological exam: Parkinsonism and focal neurological deficits Brief hearing exam Cardiovascular exam: cardiac arrhythmias, carotid stenosis Functional assessment: transferring, ambulation

26. Blood Work and Head Imaging BMP = basic metabolic panel; LFT = liver function tests; TSH = thyroid-stimulating hormone; CBC = complete blood count; MCV = mean corpuscular volume; RPR = rapid plasma regain; UA = urinalysis; MRI = magnetic resonance imaging; CT = computed tomography. Slide courtesy of Nathaniel Chin, MD. Labs BMP: kidney function and electrolytes LFTs: liver function TSH: thyroid function CBC: acute infection, anemia, MCV (vitamin deficiency, liver disease, alcohol use) Vitamin B12 level If risk factors present: HIV, RPR Other vitamins: vitamin B1, B6, D UA only if concerned about potential urinary tract infection Brain imaging MRI or CT without contrast Rule out brain mass, subdural hematoma, normal pressure hydrocephalus Evaluate for: atrophy, hippocampal atrophy, chronic small vessel disease, prior strokes

27. Advanced Biomarker Testing PET = positron emission tomography; FDG = fluorodeoxyglucose; DAT = dopamine transporter; CSF = cerebrospinal fluid. Cummings, 2019. PET scans FDG-PET Amyloid Tau DAT scan Lumbar puncture—CSF Amyloid and tau Inflammation, neurodegeneration Blood-based biomarkers Amyloid and tau Inflammation, neurodegeneration Predictive power

28. Liquid Biopsy: Blood-Based Biomarkers for AD Aß = amyloid; NfL = neurofilament light; pTau = phosphorylated tau; GFAP = glial fibrillary acidic protein; MMP = matrix metalloproteinase; sAD = sporadic Alzheimer’s disease; jAD = familial Alzheimer’s disease. Teunissen et al, 2022; Palmqvist et al, 2020; Paczynski & Day, 2022. Currently available blood-based biomarkers in the US Aß42/Aß40 Ptau217 NfL GFAP (for traumatic brain injury)

29. Genetic Testing APOE = apolipoprotein E. NIH NIA, 2023; Porsteinsson et al, 2021. Late-onset Alzheimer’s disease APOE is a risk gene, not deterministic like early-onset AD Presence of APOE4 increases risk for developing AD 1 copy of APOE4 increases risk by 2-4x 2 copies of APOE4 increases risk by 10-15x Not routinely ordered in clinical practice for diagnosis Some patients may learn APOE status from direct-to-consumer testing or from clinical trials

30. How Do MABs Work? MAB = monoclonal antibody; Fc = fragment crystallizable region; FcR = Fc receptor. Leisher et al, 2023; Zampar & Wirths, 2020. Proposed mechanisms of anti–amyloid-ß

31. Overview of 3 MABS IgG1 = immunoglobulin 1; Aß = amyloid beta; BACE = ß-site APP cleaving enzyme; AICD = APP intracellular domain. Leisher et al, 2023; Sims et al, 2023; Haeberlein et al, 2022; van Dyck et al, 2022; FDA, 2021; FDA, 2023. Aducanumab First FDA-approved therapy via accelerated approval (6/2021) Conflicting phase 3 trials Human IgG1 antibody targeting aggregated forms of Aß (oligomers, insoluble fibrils) Lecanemab First FDA-approved therapy via traditional approval (7/2023) Human IgG1 antibody targeting soluble forms of Aß (oligomers, protofibrils) Donanemab Under evaluation by FDA Human IgG1 antibody targeting insoluble Aß (fibrils, plaques)

32. General Indications, Contraindications, Administration IV = intravenous. Leqembi ™ prescribing information, 2023 ; Aduhelm ® prescribing information, 2022; Cummings, Apostolova, et al, 2023; Sims et al, 2023 . Patient population MCI and mild stage dementia Confirmed presence of amyloid Contraindications Hypersensitivity reactions Many conditions noted in the Appropriate Use Guideline Administration IV infusions every 2 weeks (lecanemab) or 4 weeks (aducanumab, donanemab)

33. Clinical Trial Outcomes ADAS-cog = Alzheimer’s Disease Assessment Scale–Cognitive Subscale; NPI = Neuropsychiatric Inventory; ADCS = Alzheimer’s Disease Cooperative Study; ADCOMS = Alzheimer’s Disease Composite Score. Haeberlein et al, 2022; van Dyck et al, 2023 ; Sims et al, 2023. Primary outcome (clinical) Clinical dementia rating sum of boxes (CDR-SB): aducanumab and lecanemab Integrated Alzheimer’s Disease Rating Scale (iADRS): donanemab Secondary outcomes (clinical and biological) Imaging: amyloid PET, tau PET, MRI CSF: amyloid, tau, neurogranin, neurofilament light chain (NfL) Blood: amyloid, tau, glial fibrillary acidic protein, NfL Clinical: MMSE, ADAS-cog13/14, ADCS-MCI-ADL NPI, Zarit Caregiver Burden (aducanumab) CDR-SB, ADCS-iADL (donanemab) ADCOMS (lecanemab)

34. Aducanumab in Early Alzheimer’s Disease adu = aducanumab. Haeberlein et al, 2022; Haberlein et al, 2020. Phase 3 Studies Led to First FDA Approval Longitudinal change from baseline in CDR-SB Longitudinal change from baseline in amyloid PET

35. Lecanemab in Early Alzheimer’s Disease van Dyck et al, 2023. Phase 3 Trial Led to FDA Approval Amyloid Burden on PET CDR-SB Score

36. Donanemab in Early Alzheimer’s Disease Leisher et al, 2023; Sims et al, 2023. Phase 3 Trial Stratified Patients Based on Tau PET Severity

37. What Is ARIA? ARIA-E = amyloid-related imaging abnormalities due to vasogenic edema, sulcal effusions; ARIA-H = amyloid-related imaging abnormalities due to microhemorrhages, superficial siderosis. Barakos et al, 2022; Hampel et al, 2023. Imaging finding on MRI brain scan observed in people treated with/not treated with MAB therapy Does not always cause symptoms ARIA-E: edema in the brain parenchyma or effusions in the sulci ARIA-H: hemosiderin deposits representing microhemorrhage in the brain parenchyma or superficial siderosis in the subarachnoid space Underlying mechanism still being investigated Believed to be driven by antibody-mediated breakdown of Aß aggregates in the blood vessels Mobilization of brain Aß plaques impairs perivascular clearance and/or initiates an immune response contributing to perivascular inflammation

38. ARIA Is Seen in All MAB Treatments ARIA = amyloid-related imaging abnormalities. Yadollahikhales et al, 2023; Lilly, 2023. Incidence Based on Data From Phase 3 Trials Aducanumab Donanemab Lecanemab Most effective dose Placebo Most effective dose Placebo Most effective dose Placebo All ARIA 41.3% 10.3% 38.9% 8% 26.6% 9.4% ARIA-E 35.2% 2.7% 26.7% 0.8% 12.6% 1.7% ARIA-H 19.1% 6.6% 30.5% 7.2% 14.0% 7.7% Discontinuation 6.2% 0.6% 15% 4.8% 6.9% 2.9% Death 1% 0.9% 0.8% 1.6% 0.7% 0.8%

39. Monitoring Process T = treatment; W = week. Cummings, Apostolova et al, 2023. MRI Monitoring for Lecanemab T1 T2 T3 T4 T5 T6 T7 T8 T14 T26 W2 W4 W6 W8 W10 W12 W14 W16 W28 W52 MRI if any symptoms suggestive of ARIA occur MRI within 1 year prior to initiation MRI prior to 5th infusion MRI prior to 7th infusion MRI prior to 14th infusion MRI for selected patients Symptoms Observed in Patients Who Develop Symptomatic ARIA Headache Confusion Visual changes Dizziness Nausea Gait difficulty Serious ARIA Seizures Status epilepticus Encephalopathy Stupor Focal neurological deficits

40. Monitoring and Management Process Appropriate Use Guidelines for Lecanemab Cummings, Apostolova et al, 2023. Severe/moderate ARIA-E or severe/moderate ARIA-H Baseline MRI has no exclusion factors MRI routine or conducted because of symptoms suggestive of ARIA ARIA-E or ARIA-H detected Symptomatic Asymptomatic Suspend treatment; clinical assessment; repeat MRI monthly Mild ARIA-E or mild ARIA-H MRI shows resolution of ARIA-E or stabilization of ARIA-H; symptoms resolve; patient wishes to continue Resume treatment with lecanemab Continue treatment with lecanemab; monthly MRI Continue treatment; discontinue monthly MRI if ARIA-E resolves or ARIA-H stabilizes Stop lecanemab therapy for any of the following: Any macro-hemorrhage More than 1 area of superficial siderosis More than 10 microhemorrhages since treatment initiation More than 2 episodes of ARIA Severe symptoms of ARIA Patient requires treatment with an anticoagulant

41. Monitoring and Management Process (cont.) NSAID = nonsteroidal anti-inflammatory agent. Cummings, Apostolova et al, 2023. Medical center resources need to manage serious or severe ARIA: Emergency department with resources to assess suspected or known ARIA MRI scanners readily available for unscheduled scanning of symptomatic patients Knowledgeable MRI readers proficient in detection and interpretation of ARIA Clinicians with experience in the management of cerebral edema or ARIA Hospital ward for monitoring and management Intensive care unit availability Electroencephalography available to inpatients Neurologist with experience in management of seizures and status epilepticus Appropriate Use Guidelines for Lecanemab Grading of Infusion Reactions Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Mild transient reaction; infusion interruption not indicated; intervention not indicated Infusion interruption but responds promptly to symptomatic treatment (eg, antihistamines, acetaminophen, NSAIDs, narcotics, IV fluids); prophylactic medication indicated for <24 hours Prolonged recurrence of symptoms following initial improvement; hospitalization may be indicated for clinical sequelae (eg, poorly controlled hypertension) Life-threatening consequences; urgent intervention indicated (may require pressor or ventilatory support) Death

42. What Is Needed to Provide MAB Treatments? Cummings, Apostolova et al, 2023. Clinician skilled in the assessment of cognition to identify individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease MRI available for baseline assessment of cerebrovascular pathology and for monitoring of ARIA Radiologists, neurologists, or other clinicians expert in identification/interpretation of cerebrovascular lesions and ARIA Amyloid PET or lumbar puncture capability to determine the amyloid status of treatment candidates Radiologists, nuclear medicine specialists, neurologists, or other specialists skilled in the interpretation of amyloid imaging or neurologists, radiologists, or other clinicians skilled in the conduct of lumbar puncture Apolipoprotein E genotyping resources Genetic expertise to counsel patients on the implications of apolipoprotein E genotyping Expertise in communicating with patients and care partners regarding anticipated benefits, potential harm, and requirements for administration and monitoring while on lecanemab Infusion settings that can be made available every 2 weeks to patients receiving therapy Knowledgeable staff at infusion sites capable of recognizing and managing infusion reactions Communication channels between experts interpreting MRIs and clinicians treating patients with lecanemab Communications channels established between clinicians treating patients with lecanemab and patient/care partner Availability of hospital resources including intensive care unit Expertise in the management of seizures and status epilepticus for patients with severe or serious ARIA Protocol with standard operating procedures for management of serious and severe ARIA

43. Emerging Treatments (cont.) Figures credit of Cummings J and de la Flor M. Cummings, Zhou et al, 2023.

44. Care Is About More Than Medications Haggerty et al, 2020; Galvin et al, 2014; Reuben et al, 2019. 8 key elements to memory care Continuous monitoring and assessment Ongoing care plan Psychosocial interventions Self-management Caregiver support Medication management Treatment of related conditions Coordination of care Collaborative care models can lead to improved patient- and family-centered outcomes

45. Modifiable Risk Factors of Dementia: Brain Health Livingston et al, 2020. Optimize chronic conditions and prevent brain injury Exercise, address mental health and reduce/eliminate alcohol Address hearing, vision, oral health; socialize (avoid isolation) and engage in mentally stimulating activities Minimize diabetes Treat hypertension Prevent head injury Stop smoking Reduce air pollution Reduce midlife obesity Maintain frequent exercise Reduce occurrence of depression Avoid excessive alcohol Treat hearing impairment Maintain frequent social contact Attain high level of education Reduce neuropathological damage (amyloid or tau-mediated, vascular, or inflammatory) Increased and maintained cognitive reserve Preventing dementia Manage MCI/dementia

46. How To Support People on DMTs Slide courtesy of Nathaniel Chin, MD. Open communication among specialties and settings Accurate and visible documentation of DMT use Leveraging electronic medical records for monitoring infusions and schedules Nurse care managers to serve as points of contact Education and awareness of condition, treatment, and potential side effects Access to clinic for adequate follow-up

47. Community Support National Care Planning Council, 2020. Working with community organizations Support for patient and families Ongoing education and providing resources Connecting with state aging services Area Agencies on Aging can provide resources and programs Community centers and senior centers Private in-home care services

48. Clinical Research Slide courtesy of Nathaniel Chin, MD. Clinical trials Pharmaceutical trials Non-pharmaceutical lifestyle trials Studies focusing on care and care partners Observational studies

49. Advanced Care Planning HC-POA = health care power of attorney; POA = power of attorney. Slide courtesy of Nathaniel Chin, MD. Medical-legal preparation HC-POA and financial POA Advanced directives and living will Understanding what is most important to a person Medical care Personal life Discussion of type of care to receive during disease Surgery Cancer screening Management of chronic medical conditions Planning for future changes Living environment

50. Key Takeaways Treating Alzheimer’s disease starts with an accurate diagnosis of syndrome, stage, and etiology Clinical tools and biomarkers will improve the diagnostic process, but nothing replaces a good history Monoclonal therapies are adding important options to care, and they will require infrastructure and teamwork Memory care is best delivered in a multidisciplinary and holistic approach, using both health care and community resources

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