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Alzheimer’s Update
Presented By:
Ashly Gray, BSN, RN
Marcella Tashjian-Gibbs, MD
Sarah May
5/11/2017
1
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
5/11/2017
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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/wpcontent/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-diseasemay-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-todementia-and-alzheimer.html)
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Genetics
• Risk appears to be somewhat higher if a firstdegree 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.
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•
(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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Treatment
Cholinesterase 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:
5/11/2017
http://www.sxc.hu/photo/1007722)
15
Treatment
Memantine
• 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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BACKGROUND
Cholinesterase 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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BACKGROUND
Memantine
• 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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BACKGROUND
Donepezil + 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
5/11/2017
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BACKGROUND
Moderate-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 513
–
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
Howard R et al. N Engl J Med 2012;366:893-903
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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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Results
Primary 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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Results
Primary 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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Results
Primary 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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Results
Factors 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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Results
Secondary 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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Results
Primary 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 highcalorie 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/silversneakersencourages-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.
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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/sitebuilder
content/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%20i
mages/GrantFunding.jpg
5/11/2017
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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/000/00
0/424/original/337abb3961a381e1ade2854730928aa6
5/11/2017
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Make-Up of the ABC
Medical 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 McDonaldTreece, Charmin Smith, and Rob
Stigers.
Image taken from:
http://www.agingcare.com/InfusionNewsSiteImages/agi
ngcare/9abbbbb9-92c4-4a24-ab83-c9713d28e060.jpg
5/11/2017
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Make-Up of the ABC
Medical Home Team
• Physician Oversight.
– Dr. Marcella TashjianGibbs, a geriatrician,
and Dr. Sara Huffer, a
neurologist are the CoMedical 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/_YhH8fDK5kU/S8Mm479yJI/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 [email protected]
- 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 References
Howard, 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
5/11/2017
61
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/memantinehydrochloride.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/vasculardementia/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
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