04/18/23 1

Alzheimer’s UpdatePresented By:

Ashly Gray, BSN, RN

Marcella Tashjian-Gibbs, MD

Sarah May

Objectives

• Provide a brief overview of dementia, including most common types

• Distinguish Alzheimer’s dementia from other common types of dementia

• Provide update on diagnosis and treatment of Alzheimer’s dementia

• Provide overview of local resources available in the greater Lafayette community, highlighting the IU Health Arnett Aging Brain Care Medical Home program and the Alzheimer’s Association

• Questions

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Dementia• Group of symptoms that

affects intellectual and social skill severely enough to interfere with activities of daily living

• One symptom alone does not indicate dementia – at least two brain functions must be affected

• Many different causes and types, Alzheimer’s being the most common

(Mayo Clinic, 2013)

(Image: http://eastsidefriendsofseniors.org/wp-content/uploads/2013/03/blog-3-26-13-dementia.jpg)

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Common Types of Dementia: Vascular

• Dementia resulting from damage caused by impaired blood flow to the brain, including stroke, heart disease, and other conditions that damage vessels and reduce circulation

• Changes in thought processes usually occur in a pattern of noticeable downward steps, unlike the gradual decline of Alzheimer’s disease

• Can also occur in conjunction with Alzheimer’s disease

(Mayo Clinic, 2011)

(Image: http://sharewithmenow.blogspot.com/2010/12/stroke.html)

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Common Types of Dementia: Frontotemporal

• Dementia resulting from atrophy and shrinkage of the frontotemporal lobes of the brain – describes a diverse group of uncommon disorders

• Symptoms vary, depending on the portion of the brain that is affected - some undergo drastic personality and behavioral changes, which can include social impropriety, impulsiveness, emotional indifference, and loss of ability to use and understand language

• Often begins at a younger age – between 40 and 70, and is often misdiagnosed as early onset Alzheimer’s disease or a psychiatric problem

(Mayo Clinic, 2011)

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Common Types of Dementia: Parkinson’s Disease

• Progressive neurological disorder affecting movement

• Characterized by tremors, bradykinesia, loss of unconscious movements, and impaired balance and posture

• Dementia usually occurs in the later stages of the disease, and is not generally responsive to medications

(Mayo Clinic, 2012)

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Alzheimer’s Disease

• A progressive type of dementia that is characterized by degeneration and destruction of the connections between neurons in the brain

• Results from formation of beta-amyloid plaques and neurofibrillary tau protein tangles

(Mayo Clinic, 2013)

(Image: http://www.diabetologica.com/2011/03/alzheimers-disease-may-actually-begin-in-the-liver-not-the-brain/

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NIA Video: Unraveling the Mystery of Alzheimer’s

Disease

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Risk Factors• Greatest known risk

factor is increasing age – risk greatly increases after age 65

• Nearly half of people age 85 and older have Alzheimer’s disease

• Women more likely to develop the disease than men, partly due to the fact that they live longer lives

(Mayo Clinic, 2013)

(Image :http://www.alz.org/braintour/healthy_vs_alzheimers.asp)

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Risk Factors• People with mild cognitive

impairment have increased risk – healthy lifestyle and strategies to compensate for memory loss in this early stage may help delay or prevent progression.

• Severe or repeated head trauma

• Factors that increase risk of heart disease may also increase risk of developing Alzheimer’s

(Mayo Clinic, 2013)

(Image: http://www.123rf.com/photo_12353999_memory-loss-due-to-dementia-and-alzheimer.html)

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Genetics

• Risk appears to be somewhat higher if a first-degree relative has the disease

• Scientists have identified three rare genetic mutations that almost guarantee a person will develop the disease

• Strongest gene found thus far: apolipoprotein e4 (APOE e4)

• Genetic mutations account for less than 5% of people with Alzheimer’s disease

(Mayo Clinic, 2013)

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Diagnosis

• No specific test that will diagnose Alzheimer’s disease

• Can only be diagnosed with complete accuracy after death, on autopsy

• Doctors rely on symptoms and results of various tests to rule out other causes of dementia - tests include mental status, neurological status, lab tests, and brain imaging (CT, MRI, PET)

• New tools for diagnosis are currently under investigation, including new approaches to brain imaging, more sensitive mental status testing, and measurement of proteins or protein patterns in blood or CSF

(Mayo Clinic, 2013)

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Recent Study on Blood and CSF Testing

• Article from Science Daily on May 29, 2013 described a Mayo Clinic study in which researchers analyzed CSF and plasma samples from 45 people – 15 with no cognitive decline, 15 with MCI and 15 with Alzheimer’s disease

• “They detected significant changes in the cerebrospinal fluid and plasma in those with cognitive decline and Alzheimer's. Most important, changes in plasma accurately reflected changes in the cerebrospinal fluid, validating blood as a reliable source for the biomarker development (Science Daily, 2013).”

• Researchers used a new technique called metabolomics – measures chemical fingerprints of metabolic pathways within the cell, such as sugars, lipids, nucleotides, amino acids and fatty acids, to detect changes in CSF and plasma.

• (Science Daily, 2013)

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Recent Study on Blood and CSF Testing

• The metabolomics gives insight into the underlying cellular processes of a disease

• “The metabolomic profiles showed changes in metabolites related to mitochondrial function and energy metabolism, further confirming that altered mitochondrial energetics is at the root of the disease process (Science Daily, 2013).”

• Researchers hope that the identified changes in metabolic pathways can eventually be used on a larger scale for early diagnosis and monitoring of Alzheimer’s disease

(Science Daily, 2013)

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TreatmentCholinesterase Inhibitors

• This includes donepezil, galantamine, and rivastigmine, which work to boost levels of acetylcholine by inhibiting acetylcholinesterase, ultimately increasing cholinergic function

• Can level out symptoms and delay progression for a time, but less than half of people will show improvement

(Drugs.com, 2009)

(Mayo Clinic, 2013)

(Image: http://www.sxc.hu/photo/1007722)

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TreatmentMemantine

• NMDA (N-methyl-D-aspartate) receptor antagonist

• Slows progression of symptoms in those with moderate to severe Alzheimer’s disease

• Sometimes used in combination with a cholinesterase inhibitor, and can sometimes help with side effects

(Drugs.com, 2009)

(Mayo Clinic, 2013)

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DOMINO TRIAL

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What is this trial about?- Many trials showing benefit of cholinesterase

inhibitors for treatment of mild to moderate dementia

- What about treatment benefits after progression to moderate to severe disease?

- 295 community dwelling patients with a score of 5-13 on MMSE, treated with donepezil x 3 months

- 4 groups: continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, continue donepezil and start memantine

- Co-primary outcomes were scores on MMSE and Bristol Activities of Daily Living Scale (BADLS – 0-60 with higher scores indicating greater impairment)

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BACKGROUNDCholinesterase Inhibitors

• Most studies evaluating cholinesterase inhibitors for treatment of Alzheimer’s disease have focused on MILD TO MODERATE disease

• Guidelines recommend treatment with a cholinesterase inhibitor in dementia

• Some guidelines recommend discontinuation of the medication when disease becomes severe

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BACKGROUNDMemantine

• Evidence of efficacy of memantine primarily shown in patient’s with moderate to severe Alzheimer’s disease

• Areosa SA, Sherriff F, McShane R. Memantine for Dementia. Cochrane Database Syst Rev 2005;3:CD003154

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BACKGROUNDDonepezil + Memantine

• Findings of a study showing that combination therapy with memantine and a cholinesterase inhibitor was more effective than treatment with a cholinesterase inhibitor alone have not been replicated

• Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I. Memantine treatement in patients with moderate to severe Alzheimer disease already receiving donepezil; A randomized control trial. JAMA 2004;291:317-24

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BACKGROUNDModerate-to-Severe Alzheimer’s

• Results from randomized control trials involving patient’s with moderate to severe disease SUGGEST that cholinesterase inhibitors are associated with improvements in cognition and function

• All the trials looking at severe Alzheimer’s disease have involved nursing home residents

• None of the trials focusing on moderate or severe Alzheimer’s have looked at continuing treatment with cholinesterase inhibitors in patients already taking the medication

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BACKGROUND (cont.)Moderate-to-Severe Alzheimer’s

• Studies have shown that continued treatment after disease progresses is ASSOCIATED with an increase in adverse outcomes– Syncope– Need for insertion of pacemakers– Hip fractures

• Gill SS, Anderson GM, Fischer HD, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: A population based cohort study. Arch Intern Med 2009;169:867-73

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Objectives of the Domino Trial

• Community living patients with Alzheimer’s disease with moderate to severe dementia

• Patients already receiving donepezil

• Over period of 52 weeks to investigate:– If continuation of donepezil as compared with

discontinuation would be associated with better cognition and function

– To test whether memantine as compared with placebo memantine would be associated with better cognition and function

– To test whether a combining donepezil and memantine would provide additive or synergistic benefits

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Methods• Multicenter, double blind, placebo-controlled, clinical trial

• Outcomes assessed for 52 weeks

• Community residents who had caregivers who lived with the patients OR visited at least daily

• Eligible participants met standardized clinical criteria for probable/possible moderate or severe disease – Score on MMSE of 5-13– McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clincal

diagnosis of Alzheimers disease: report of the NINCDS-ADRADA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939-44

• Had been on donepezil for at least 3 months

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Methods (cont.)

• Each eligible patient’s prescribing clinician was considering a change in drug treatment– Such as stopping donepezil or

introducing memantine– Based on National Institute for Health

and Clinical Excellence (NICE) guidelines

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Study Procedures• Participants randomly assigned to one of four groups

– Continuation of donepezil• Dose of 10 mg/day, placebo memantine starting in

week1– Discontinuation of donepezil

• 5 mg of donepezil weeks 1-4; placebo donepezil starting in week 5; placebo memantine starting in week 1

– Discontinuation of donepezil and initiation of memantine• Donepezil 5 mg weeks 1-4; placebo donepezil week 5;

initiation of memantine 5 mg week 1; increased 5 mg/week to full dose of 20 mg by week 4 on

– Continuation of donepezil and initiation of memantine• Donepezil 10 mg daily; memantine 5 mg week 1,

increased to total dose of 20 mg daily by week 4

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Study Procedures (cont.)Logistics

• Groups stratified based on following:– Center (15 participating centers)– Duration of donepezil treatment before entry – 3-6

months vs. greater than 6 months– Baseline MMSE score – 5-9 indicating severe

disease vs. 10-13 indicating moderate disease– Age - < 60 years old, 60-74 years old, or >75

years old– Donepezil and memantine as well as matched

placebo tablets provided by manufacturers– Patients, caregivers, clinicians, outcome assessors

and investigators were unaware of treatment assignments

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Outcome Measures• Co-primary outcomes

– Scores on the MMSE– Scores on the caregiver-rated Bristol Activities of Daily

Living Scale (BADLs – higher scores indicating greater impairment)

• Secondary outcomes– Scores on the Neuropsychiatric Inventory (higher

scores indicating increased behavioral and psyhological symptoms

– Scores on the DEMQOL-Proxy (higher scores indicating better patient health-related quality of life)

– General Health Questionaire 12 (measures caregiver health status with higher scores indicating increased psychological symptoms in nonprofessional caregivers)

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Baseline Characteristics of the Participants, According to Treatment

Group

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Howard R et al. N Engl J Med 2012;366:893-903

Results

• From February 2008 to March 2010 there were 295 patients enrolled

• Recruitment was slower than expected

• Recruitment was not extended because the public funder (UK Medical Research Committee) felt the disadvantages of delaying reporting of results outweighed the benefits of increasing the power of the study

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ResultsPrimary Outcomes - Donepezil

• Patients assigned to continue donepezil (compared with those assigned to discontinue donepezil) had higher MMSE by an average of 1.9 points

• Patients assigned to continue donepezil had scores on BADLs that were lower by an average of 3 points

• This was statistically significant for MMSE and nearing significance for BADLs

• Of note, there was significant differences in treatment efficacy over time – with LESS benefit apparent at the 6 week assessment than at later points in the study

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ResultsPrimary Outcomes - Memantine

• Patients receiving memantine (as compared to those receiving placebo memantine) had scores on MMSE that were higher by an average of 1.2 points

• Patients receiving memantine had scores on the BADLs that were lower by an average of 1.5 points

• Both results smaller than the minimum statistically significant difference

• Numbers reflect the average effect among patients assigned to continue donepezil as well as those assigned to discontinue donepezil.

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ResultsPrimary Outcomes – Donepezil +

Memantine

• For both drugs, the benefits with respect to scores on MMSE and BADLs appeared to be larger in the ABSENCE of the other agent– Differences were NOT statistically

significant

• No significant benefit of adding memantine to donepezil with respect to scores on MMSE or BADLs

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ResultsFactors Effecting Primary Outcomes

• Severity of dementia at entry largely influenced effect of donepezil on MMSE– Larger benefits observed in patients with

moderate dementia (MMSE 10-13)– Average difference in scores between groups

assigned to continue vs. discontinue donepezil in moderate dementia was 2.6 points, and in severe was 1.3 points

• Severity of dementia did not have an effect on BADLs scores

• Severity of dementia did not have an effect on MMSE or BADLs scores in patients on memantine

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ResultsSecondary Outcomes - NPI

• Patient’s receiving memantine (in comparison to placebo memantine) had lower scores on the NPI – By a factor of 4 points (clinical significance 8

pts)

• No difference between continuing or discontinuing donepezil

• Addition of memantine to donepezil (in comparison to placebo memantine) had lower scores– Average of 5.1 pts – Did seem that donepezil + memantine had

greater improvement than either agent alone (not statistically significant)

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ResultsPrimary Outcomes – GHQ-12

• Continuation of donepezil and memantine (in comparison to placebo memantine) – Larger decreases in score for GHQ-12

caregiver health scale– Less psychological symptoms in

caregivers– Not clinically significantly

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Other Measures of Treatment Sensitivity

• Patients who withdrew from treatment after the 18 week visit or after the 30 week visit had lower MMSE, and higher BADL scores at their last visit prior to withdrawal

• Patients who withdrew at any point had lower MMSE and higher BADL scores after withdrawal than those who continued treatment

• Sensitivity analysis done and results similar to primary analysis

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Conclusions

• There are cognitive and functional benefits of continuing donepezil over the course of 12 months– Difference in MMSE exceeded clinical significance– Difference in BADLS was less than the minimum to

meet clinical significance

• Initiation of memantine also associated with significantly better cognitive and functional function– Magnitude of benefit was smaller than donepezil– For memantine alone difference did not reach

statistical significance

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Conclusions (cont.)

• Memantine (compared with placebo) was associated with fewer behavioral symptoms

– Measured by NPI– Not statistically significant

• Memantine + donepezil was not superior to donepezil alone with respect to any primary or secondary outcomes

• Improvements in cognition and function associated with donepezil and memantine were small relative to overall decline of ALL patients

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ALZHEIMER’S DISEASE LIFESTYLE

RECOMMENDATIONS

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Diet and Exercise• Maintain adequate

nutrition – people with Alzheimer’s often forget to eat or drink, lose interest in cooking due to decreased comprehension, or have little or no appetite.

• Supplement diets with high-calorie nutritional shakes for those who have decreased appetite

• Push fluids, avoiding caffeine

(Mayo Clinic, 2013)

(Image: http://www.alzdallas.org/lifestylechanges/)

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Diet and Exercise

• Create a safe environment to facilitate and prolong independence and mobility – clear pathways within the home, handrails by steps, etc.

• Regular exercise - helps maintain mobility

(Mayo Clinic, 2013)

(Image: http://www.todayspulse.com/news/news/local/silversneakers-encourages-older-adults-to-engage-i/nWZMH/)

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Socialization• Socialization and intellectual

stimulation can help preserve mental function.

• Activities such as puzzles, reading, games, and other mentally stimulating exercises can help people with Alzheimer’s remain as functional as possible

• Participating in group activities and attending support groups can help prevent loneliness and hopelessness

(Mayo Clinic, 2013)

(Image: http://www.drweilblog.com/home/2011/7/6/socialize-for-a-better-brain.html)

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Community Resources

• IU Health Arnett Aging Brain Care Medical Home

• Area IV Agency on Aging

• Several home health agencies, both medical and non-medical (ex: IU Health Arnett Home Care, Franciscan St. Elizabeth Home Care, Physicians Homecare, Mulberry Home Care, Comfort Keepers, Home Care By Design, BrightStar)

• Alzheimer’s Association

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What is ABC Medical Home?

• Has been operating in the Wishard system for the last two years, mainly at the Primary Care Center, as a collaborative care model for older adults.

• Target population: adults age 65 and older with depression, dysthymia, and/or any type of dementia, memory loss, or cognitive impairment.

• Expanded to the IU Health Arnett system in December 2012.

• Currently limited to 500 patients – because of this, we can only enroll patients with IU Health Arnett PCPs (specialists do not count)

• Unique characteristics include home-based assessments of patients’ cognitive, behavioral, psychological, and functional status coupled with protocol-driven interventions.

What is ABC Medical Home?

• All interventions are done in collaboration with the primary care provider – the ABC medical home does not assume care of the patient, but rather brings additional resources to the table for the primary care provider.

Image taken from: http://www.southhavenfamilyphysicians.org/sitebuildercontent/sitebuilderpictures/pcmh.jpg

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ABC Funding• Funded through a

three-year grant from the Centers of Medicare and Medicaid Services (CMS)

• Through this grant, we are able to offer the program at no cost to the patient.

Image taken from: http://www.incompasstesting.com/InCompass%20IT%20images/GrantFunding.jpg

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ABC Goals

• Main goal is to decrease urgent care and emergency department visits, as well as hospitalizations.

• Ultimately, it is hopeful that the ABC Medical Home program will become a service that is offered by IU Health Arnett and/or covered by Medicare.

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Key Elements of the ABC Medical

Home Evaluation

• Once potential patients are identified, they will be contacted by phone to set up an in-home assessment. The standardized evaluation will include:– Assessment of the patient’s cognitive, behavioral,

and functional status (with the Healthy Aging Brain Center (HABC) Monitor tool, a 31-item validated questionnaire which takes approximately 6 minutes to administer).

– Mini-Mental Status Examination (MMSE)– Assessment of the patient’s mood (with the Patient

Health Questionnaire depression scale (PHQ-9). – Medication reconciliation– Caregiver stress and symptom assessment

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Make-Up of the ABC Medical Home Team

• Care Coordinator (CC) – Ashly Gray, BSN, RN is the Care Coordinator for the IU Health Arnett ABC program. The Care Coordinator functions as the leader of the team, especially for clinical issues.

• Social Worker – Cassie Hixson, MSW is the social worker for the IU Health Arnett ABC program. Currently, she splits her time between the IU Health Arnett team and the Wishard team. She is contracted to IU Health through CICOA.

Image taken from: http://s3.amazonaws.com/kmacdn/attachments/000/000/424/original/337abb3961a381e1ade2854730928aa6

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Make-Up of the ABCMedical Home Team

• Care Coordinator Assistants (CCA) – These members are analogous to medical assistants. They have all been carefully selected and trained in a highly structured program to assure adequate expertise to perform their required functions. The CCAs on the IU Health Arnett team are: Lauren Fleming, Stacey Sipos, Tilara McDonald-Treece, Charmin Smith, and Rob Stigers.

Image taken from: http://www.agingcare.com/InfusionNewsSiteImages/agingcare/9abbbbb9-92c4-4a24-ab83-c9713d28e060.jpg

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Make-Up of the ABCMedical Home Team

• Physician Oversight. – Dr. Marcella Tashjian-

Gibbs, a geriatrician, and Dr. Sara Huffer, a neurologist are the Co-Medical Directors of the IU Health Arnett ABC Medical Home team.

– Most importantly, each primary care provider is an intimate part of the ABC Medical Home.

Image taken from: http://2.bp.blogspot.com/_YhH8fDK5-kU/S8M-m479yJI/AAAAAAAAAHk/ba1nKdo0oBs/s1600/brain.jpg

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Feedback to Primary Care Provider

• The key to this collaborative care model is primary provider involvement.

• Clinical information collected during the ABC assessment is communicated back to the primary care provider (or the provider’s designee) along with possible recommendations.

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Referring to ABC

• To refer a patient to ABC:

- Call Ashly Gray at 765-838-6383

- Email Ashly Gray at graya2@iuhealth.org

- Epic referral (if applicable) – Refer/Consult

Aging Brain Care

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ALZHEIMER’S ASSOCIATION

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Alzheimer’s Association:A Trusted Partner for your Patient’s with

Dementia

– We help providers help their families through:•Dementia education, resources, and support•Information and referral•Helping patients with Alzheimer’s disease

and other dementia’s stay safe in and away from home

• ALL programs and services for families are provided free of charge

Benefits for Physicians and Other Healthcare Providers

• It takes a lot of time to educate families about AD• The Alzheimer’s Association has the time to provide the information,

support and resources families need to face the challenges inherit of dementia, allowing the provider more time to focus on the healthcare management of the person

• A dx of dementia increases the challenges of managing other health conditions• Through early intervention, the Alzheimer’s Association can help

caregivers develop a plan for the future and receive the dementia education they need to be the best caregiver possible. Some examples include:

• Tips/strategies for medication management• Tips/strategies for proper nutrition/hydration • Staying Safe (wandering, driving, fall risk, home safety, etc)

• The outcome is better care management, reducing the chances of hospital admission or readmission from co-morbidities or safety hazards such as falls

Partnering with the Alzheimer’s Association

• The Alzheimer’s Association can partner in whatever way is most helpful for the provider

• All requested materials are provided free of charge, including patient packets• Patient packets are a convenient source of distributing information

about Alzheimer’s and the Alzheimer’s Association to patients/caregivers

• Referral to the Alzheimer’s Association is simple– A referral can be as simple as providing the

patient/caregiver with the Association’s 1-800-272-3900 Helpline, or utilizing the Rapid Referral system

Questions?

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Trial ReferencesHoward, R MD, et al. Donepezil and Memantine for Moderate-to-Severe

Alzheimer’s Disease . NEJM 2012;366;10: 893-903

Areosa SA, Sherriff F, McShane R. Memantine for Dementia. Cochrane Database Syst Rev 2005;3:CD003154

Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I. Memantine treatement in patietns withmoderate to severe Alzheimer disease already receiving donepezil; A randomized control trial. JAMA 2004;291:317-24

Gill SS, Anderson GM, Fischer HD, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: A population based cohort study. Arch Intern Med 2009;169:867-73

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clincal diagnosis of Alzheimers disease: report of the NINCDS-ADRADA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939-44

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Resources

Drugs.com. (2009). Donepezil. Retrieved from: http://www.drugs.com/cdi/donepezil.html

Drugs.com. (2009). Memantine hydrochloride. Retrieved from: http://www.drugs.com/ppa/memantine-

hydrochloride.html

Mayo Clinic. (2013). Alzheimer’s disease. Retrieved from:

http://www.mayoclinic.com/health/alzheimers-disease/DS00161

Mayo Clinic. (2013). Dementia. Retrieved from: http://www.mayoclinic.com/health/dementia/DS01131

Mayo Clinic. (2011). Frontotemporal dementia. Retrieved from:

http://www.mayoclinic.com/health/frontotemporal-dementia/DS00874

Mayo Clinic. (2012). Parkinson’s disease. Retrieved from:

http://www.mayoclinic.com/health/parkinsons-disease/DS00295

Mayo Clinic. (2011). Vascular dementia. Retrieved from: http://www.mayoclinic.com/health/vascular-

dementia/DS00934

National Institute on Aging (NIA). (2013). Inside the brain: Unraveling the mystery of alzheimer’s disease

(video). Retrieved from: http://www.nia.nih.gov/alzheimers/alzheimers-disease-video

Science Daily. (2013). Blood test to diagnose alzheimer’s in earliest stage. Retrieved from:

http://www.sciencedaily.com/releases/2013/05/130529111236.htm