Dementia Update for Primary Care:

Detection, Diagnosis and Management

Kristoffer Rhoads, PhDClinical Neuropsychologist

Associate Professor, Department of Neurology

Memory and Brain Wellness Center

Harborview Medical Center/University of Washington School of Medicine

Seattle, WA 6/9/17

Presentation Overview

• Context

• Regional Data

• WA State Plan for AD

• Clinical Integration

• Detection

• Multidisciplinary management

• Multimodal treatment

• Resources

• Future Directions

“Should we begin to think of lifelong control of Aβ metabolism in the same way that we

now think of lifelong control of cholesterol metabolism? The lesson of the DIAN study and

of the study on the protective APP mutation is that reduction of the risk of late-life

dementia requires a long-term and possibly lifelong effort.” S. Gandy MD N Engl J Med 2012, Nature 2012

Early Detection and Intervention

Years

Cognitive

Function

Presymptomatic

Prodromal

Dementia

~5-20? years

~1-10? years

~2-20 years

Progression of Alzheimer’s Disease

Mild Cognitive Impairment

Progression of Alzheimer’s Disease

Years

Cognitive

Function

Presymptomatic

MCI

Dementia

gradual

accumulation of

neuropathology

2017 Facts and Figures

• 5,500,000 Americans with Alzheimer’s

• 10% general risk after age 65

– 65-74 = 3%

– 75-84 = 17%

– 82+ = 32%

Dementia, Healthcare & Economic Burden

• Third most costly health condition in 2017

– Annual cost ~ $259 billion Alzheimer’s Association, Alzheimers Dement 2017

– $172 billion in 2010 Davis, J, Hsiung, GY, Lui-Ambrose, T. Br. J of Sports Med, May 2011, Bateman et al. NEJM 2012

• $818 Billion worldwide in 2016 Prince et al, 2016

– $604 Billion worldwide in 2010 Wimo & Price 2010

• $238 billion/year = (T2DM+CAD+HTN+CVA)

• 83% of US workers obese or w/chronic condition

– > $1 trillion/year lost economic activity and productivity

• $1 prevention = $5.60 savings RWJ Public Health Portfolio 2011

Dementia, Healthcare & Economic Burden

• Major risk factor for critical patient safety issues

– Post-op delirium

– Hospital delirium

– Falls

– Rapid readmission rates Wimo & Price 2010

Alzheimer’s in Washington State

• 100,000 cases in WA

– 40% increase by 2025

• 3rd leading cause of death

– 3rd highest rate in the US

– Mortality rate= 47.4

• Who provides care?

– 335,000 unpaid caregivers

– 382,000,000 hours = $4.83 billion

– $227 billion in additional health care costs

Alzheimer’s Association. 2017 Alzheimer’s Disease Facts and Figures. Alzheimer’s & Dementia 2015;11(3)332+

Alzheimer’s Washington State Plan

• October 2013- Governor’s Aging Summit

• February 2014 - SSB6124

• July 2014 - AD Working Group

• January 2016 - Plan released

• February 2016 - Plan accepted by Senate

• April 2016 - Dementia Action Collaborative

• January 2017 -First “products” released & Bree

Collaborative Meeting

13

• Goals – broad visionary statements

• Strategies – high level plans to achieve the goals

• Recommendations –specific responses or actions

Plan Development

14

A Phased Approach

Recommendations identified by implementation time…

• Short-term: within 2 years

• Mid-term: 3-4 years

• Long-term: 5 years or more

…and the likely need for additional resources

• No additional resources needed

• Additional funding needed

• Additional legislation needed

15

1. Increase public awareness

2. Prepare communities

3. Ensure well-being and safety

4. Ensure family caregiver supports

5. Identify dementia early and provide dementia-capable, evidence-based health care

6. Ensure dementia-capable long-term services and supports

7. Promote innovation and research

Aspirational Goals

16

Dementia Action Collaborative

• Public-private partnership

• 37 Stakeholders

∙ Persons with dementia

∙ Family caregivers

∙ Medical providers, clinicians, researchers

∙ Legislators

∙ DSHS, HCA, DOH

∙ Alzheimer’s support organizations

• Subcommittee and Project Team Members

17

The DAC at Work

• Priorities in 2016

∙ Focus on what can be done through heightened collaboration with existing resources

∙ Sustain momentum and awareness by engaging partners (JLEC and others)

18

• Develop a website “point of access” portal

• Compile educational materials about safety

• Identify elements of dementia-friendly communities

• Inform and educate about healthy aging and brain health

Recommendations in Motion – 2016Public Awareness and Community Readiness

Subcommittee

19

• Develop a “roadmap” for family caregivers

• Expand and promote early stage groups

• Identify and engage leaders of diverse populations to explore needs

• Identify and promote existing models of care coordination

Recommendations in Motion - 2016Long-Term Services and Supports

20

• Convene expert panel to identify and endorse evidence-based standards for diagnosis, treatment, supportive care, and advanced planning

• Identify and recommend validated cognitive screening tools

• Promote understanding and effective use of Medicare Annual Wellness Visit

Recommendations in Motion – 2016Health and Medical Subcommittee

Dementia Action Collaborative

• Public-private partnership

• 37 Stakeholders

∙ Persons with dementia

∙ Family caregivers

∙ Medical providers, clinicians, researchers

∙ Legislators

∙ DSHS, HCA, DOH

∙ Alzheimer’s support organizations

• Subcommittee and Project Team Members

Aspirational Goals

1. Increase public awareness

2. Prepare communities

3. Ensure well-being and safety

4. Ensure family caregiver supports

5. Identify dementia early and provide dementia- capable,

evidence-based health care

6. Ensure dementia-capable long-term services and supports

7. Promote innovation and research

WA State Plan/Dementia Action Collaborative

5. Identify dementia early, and provide dementia-capable,

evidenced based health care.

A. Promote early detection, diagnosis and treatment.

1. Identify and recommend validated cognitive screening tools

B. Identify and endorse a set of evidenced-based

standards of care for dementia to promote high quality

health care for people with dementia in Washington

State.

1. Convene expert panel to identify and endorse evidence-based

standards for diagnosis, treatment, supportive care, and

advanced planning

C. Promote understanding and effective use of Medicare

Annual Wellness Visit

The Dr. Robert Bree Collaborative

To align care delivery with existing evidence-

based standard of care for diagnosis, treatment,

supportive care, and advance care planning

within primary care for patients with Alzheimer’s

disease or other dementias and their families

and caregivers while decreasing variation in

quality of treatment across the state of

Washington.

Bree Collaborative: Workgroup Members

• Chair: Kristoffer Rhoads, PhD, , Memory and Brain Wellness Center, UW Medicine

• Kimiko Domoto-Reilly, MD, Alzheimer's Research Center, UW Medicine

• Richard Furlong, MD, Primary Care, Virginia Mason Medical Center

• Barak Gaster, MD, Professor of Medicine, UW Medicine

• Kelly Green, MSW, Social Worker, Evergreen Health

• Debbie Hunter, Family Caregiver

• Nancy Isenberg, MD, MPH, FAAN, Neurologist, Virginia Mason Medical Center

• Arlene Johnson, Family Caregiver

• Kerry Jurges, MD, Primary Care, Confluence Health

• Eric Larson, MD, MPH, Vice President for Research and Health Care Innovation, Kaiser

Foundation Health Plan of Washington

• Todd Larson, Family Caregiver

• Myriam Marquez, Patient Advocate

• Shirley Newell, MD, Chief Medical Officer, Aegis Living

• Darrell Owens, DNP, ARNP, Clinic Chief, Director, University of Washington Outpatient

Primary, Palliative and Supportive Care Program

• Tatiana Sadak, PhD, ARNP, UW Medicine

• Bruce Smith, MD, Medical Director, Regence Blue Shield

Bree Collaborative: Recommendations

• Case Detection

– Importance of early detection

– At risk populations

– Opportunities

– Clinical Pathways

• Diagnosis

• Referrals

– Consultation

• Rural care settings

• Interventions

– “Now what?”

Draft Recommendations

Diagnosis Propose two-step process: initial test and follow-up

appointment

Current State: Issues with memory and cognition are addressed if they are

brought up by the patient or family member(s). The primary care provider

may be unsure as to screening tools, Federal or State requirements, or next

steps if a patient or family members brings up concerns with memory and

not feel comfortable discussing cognitive issues.

Steps Toward Goal: Screening for at-risk populations, clear clinical pathway

for people who screen positive including through the Medicare Annual

Wellness visit.

Goal for Usual Care: Healthy adults with mild cognitive impairment (MCI) or

dementia are detected at an early stage, targeting early evidence-based

interventions. Primary care providers are clear on the value of early

detection as well as requirements and feel supported and comfortable

truthfully discussing cognitive issues.

Draft Recommendations

Diagnosis

Operationalizing the goals (TO BE ALIGNED WITH DEMENTIA

ACTION COLLABORATIVE POSITION PAPER)

• Clear guidelines on how to make the diagnosis and how to

discuss this with the patient and family.

• Clear expectation that the provider will truthfully discuss the

diagnosis with the patient and family.

• Cognitive screening by direct observation with due consideration

of information obtained via beneficiary reports and concerns

raised by family members, friends, caretakers, or others is

assessed as part of the Medicare Annual Wellness Visit.

• Using a standard tool

• Specific elements to include in a work-up for people exhibiting

symptoms- what is the evidenced-bases standard?

Draft Recommendations

Referral Infrastructure

Slide 29

• Current State: Clinician may diagnose dementia or may refer to

neurologist for diagnosis (depends on factors like patient complexity,

clinician’s comfort level, and/or available resources)

• Steps Toward Goal: Primary care provider, who has an existing

relationship with the patient and will be following them over time,

diagnoses and treats the patient. Primary care provider involves a

neurologist as needed for consultation and support or for differential

diagnosis. Patients and families are offered information about

available community supports like Alzheimer’s Association services.

• Goal for Usual Care: Patient and family members receive

coordinated care as part of an interdisciplinary team. This may

include support staff in primary care provider office, specialists, and

community partners.

Draft Recommendations

Offering Interventions

Slide 30

• Current State: Significant variability in interventions and

support offered after diagnosis and throughout the

disease. Patients and families are not consistently

informed of treatment options, community services, or an

answer to the “I have a diagnosis, what do I do now?”

question

• Steps Toward Goal: There is a clear pathway for

interventions and supports to offer at different stages

throughout the disease process.

• Goal for Usual Care: Evidence-based interventions are

initiated upon diagnosis. The patient is able to participate

in a dementia-friendly health care system and community

throughout the disease, etc.

ADWG State Plan

• Public Input Survey

– N= 2,259

– 55% indicated difficulty getting a diagnosis

– 72% indicated their PCP as first point of contact/information

– 20% were given no information

– 14% received information about resources

– 7% actively referred to agencies

Basic Assessment of Dementia

• Interview/History

• Physical exam

• Neurological exam

• Cognitive assessment

• Functional status

• Depression assessment

• Laboratory

• Neuropsychological evaluation

• Neuroimaging

• Repeat if unclear

– 6-12 months

Assessment: History

– Context and Premorbid abilities

• Education, occupation, function

• Change from previous levels of function

– Onset & Progression

• Gradual vs. datable, insidious vs. sudden

• Rate, direction, fluctuations

– Impact on functioning

• Occupational, IADLs, ADLs, social, relational, etc

– Sleep and related disorders

• Quantity, quality, medications, supplements

– Save the sensitive questions until rapport has been built

• Alcohol and marijuana

• Driving

– Provide a venue for independent information from a collateral

– Repeat

• Within, between, across visits

– Sets the stage for screening

Assessment: Cognitive Screening

• In primary care settings, only <50% of patients

with dementia are diagnosed– Critical information for other providers/care team members, esp.

if the PCP is unavailable

• Better diagnostic aids are needed

• Accurate

• Brief

• Cost effective

Connoly et al, Aging and Mental Health, 2011; Mattson, et al. JAMA; 302(4):385-393.

Lopponen M, et al. Age Ageing 2003;32(6):606-612.

ADWG State Plan

• Provider Input Survey

– N= 247

– 77% indicated screening as very important

• 57% have organizational guidelines

– 46% unaware of cognitive screening component to AWV

– 55% screen when clinical concern

• 20% screen annually

– 65% use MMSE

– 57% cite time as main barrier

Cognitive Screening Measures

• MMSE (Folstein et al, 1975)

• Sensitivity = 66-73%

• Specificity = 87-92%

• Mini-Cog (Borsen et al., 2000)

• Sensitivity = 65-85%

• Specificity = 87-91%

• MoCA (Nazreddine et al., 2005)

• Sensitivity = 90-100%

• Specificity = 87-90%

Virginia Mason Cognitive Screen

• Capitalizes on active ingredients

• Recall, clock, fluency

• 3 minutes

• Can be administered by MA/RN

• Part of larger provider toolkit

• Triage tool

• Order sets

• Imaging

• Referrals

Screening: VMCS

• VM validation sample (N=150)

• GIM

• Neurology, referred by GIM

• Age 55+

• Vascular risk factors

• Subjective/objective memory concerns

• Consensus diagnosis

• Labs, neuro, imaging, neuropsych

Screening: VMCS

• Equivalent sensitivity in AD

Minicog = .69

MoCA = .87

VMCS = .85

Screening: VMCS

• Equivalent sensitivity in all dementia (AD,VaD, mixed)

Minicog = .72

MoCA = .86

VMCS= .88

Screening: VMCS

• Equivalent sensitivity in any impairment (MCI +)

Minicog = .64

MoCA = .78

VMCS = .80

Cognitive Assessment Toolkit

• Roll out integration into Medicare AWV

• GIM Dementia Care Pathway

• Follow up discussions/counseling, esp. if

patient/family are not ready for referral

• Triggers labs, additional evaluations incl. driving

• Order sets, minimize/avoid benzodiazepines,

antihistamines, anticholinergics, opioids, alcohol

• Referral to specialty services

• Validation in specialty clinic populations

• Complex spine surgery

• Orthopedic surgery prescreen

Detection – Now What?

Cognitive Impairment Care Planning

• G0505 Code • Cognition-focused evaluation

• Medical decision making

• Moderate or high complexity

• Functional assessment

• Decision-making capacity

• Standardized dementia staging

• Medication reconciliation and review

• Evaluation of neuropsychiatric symptoms

• Evaluation of safety

• Caregiver assessment

• Advance care planning

• Palliative care needs

• Creation and review of a care plan

• RVU = 6.64

• Physician work = 3.44

• CMS average payment = $238.30

Laboratory Assessment

• Blood

– CBC, chemistry

– TSH

– B12, folate

– Vitamin D

– Syphilis serology

• Genetic

– Perhaps & only with counseling

• CSF

– Ab: tau

Neuroimaging

• MRI = most sensitive/robust measure of rate of change– AD, MCI and healthy controls

– MRI Volumetric analysis

- Hippocampus, ventricles, comparable

- Atrophy = common outcome measure in AD clinical trials

• [F18]flouro-deoxyglucose (FDG)–PET

• SPECT

• Pittsburgh compound B (PiB)-PET

• Florbetapir (Amyvid) imaging • FDA approved in April 2012

• Not conclusive

• ~15% of patients with dementia are difficult to diagnose

• Need specialized training to read Amyvid studies for

• Sensitivity 92% ; specificity 95%

• Diffusion Tensor Imaging

MRI Volumetric Analysis

• Significant difference in hippocampal

volumes(HV) between control, MCI, and AD

– MCI HV average 86% of normal control HV

– AD HV average 78% of normal control HV

• Annual HV loss: Brain. 2009 Apr; 132(4): 1067–1077

– Normal 0.8% / yr

– MCI 2.6% / yr

– AD 4.4% / yr

– Modulated by genetics and biomarkers

MRI Volumetric Analysis

FDG-PET Normal vs AD

Amyvid Imaging

• When is it useful?

▪ Neurological differentials

▪ Screening is normal, but patient is not

▪ Identification of strengths/weaknesses

▪ Sets the stage for rehab/treatment

▪ Disease progression

▪ Medication/treatment response

▪ Questions about function/IADLs

▪ Capacity assessment

▪ Driving

▪ Testamentary

▪ Decision making

Neuropsychological Assessment

Prevention and Interventions

• Treatment of Midlife Modifiable Risk Factors

• Diabetes

• Hypertension

• Hypercholesterolemia

• Obesity

Intervention Targets in AD

Years

Cognitive

Function

Presymptomatic

MCI

Dementia

gradual

accumulation of

neuropathology

Presymptomatic /

MCI

decrease

neuropathology

Environmental Risk Reduction

Barnes & Yaffe 2011

Prevention and Interventions

• Treatment of Modifiable Risk Factors

• Cardiovascular

• Sedentary lifestyle

• Sleep disorders/disruption

• Alcohol

• Cardiovascular Exercise

• Cognitive Activation and Rehabilitation

• Dietary Interventions

• Meditation/Mindfulness-Based Stress Reduction

• Community Engagement and Socialization

• Early interdisciplinary involvement

Motivational Enhancement

Erickson et al., PNAS 2011

Aerobic Exercise Reduces Tau Protein in Older Adults

with Mild Cognitive Impairment (Baker et al., 2015)

• 65 sedentary adults

• 55-89 years old

• 6-month randomized controlled trial

• Aerobic exercise (70-80% max HR) vs stretching

(<35%)

• 45-60 minutes four times per week

• Reduced CSF tau

• Most prominent in age 70+

• Improved perfusion in frontal and temporal lobes

• Improved memory, attention and executive function

Prevention and Interventions: Exercise

v

• N = 923

• Age 58-98

• 4.5 years

• DASH + Mediterranean

• One glass of wine

• 53% reduction in incidence

• Alcohol

• 1-2 servings a day for men; 1 for women

• Red wine

• Grape seed extract

• Pomegranate juice

• Minimal if any alcohol use once impairments evident

• Smoking CESSATION

Prevention and Interventions

Palliative Care and Dementia

Palliative Care and Dementia

Palliative Care and Dementia

Merel, Clin Geri Med 2014

Back to the Basics

• Need to encourage discussion and manage even

the basics of end of life care– Feeding tubes in advanced dementia

– Advanced directives

• Issue of capacity

– POLST

– Living will

– Durable Power of Attorney

– Estate issues

– Elder law referrals

UW Memory and Brain Wellness

• A consortium of

– Alzheimer Disease Research Center (NIA)

– Pacific Northwest Udall Center (NINDS)

– Memory and Brain Wellness Clinic

• Links state-of-the-art clinical evaluation and care with

research programs in Alzheimer’s and related disorders

MBWC – Interdisciplinary Approach

• Neurology

• Geriatrics

• Psychiatry

• Neurogenetics

• Neuropsychology

• Nursing

• Social Work

Referrals & Orders

• Neurodegenerative (possible to suspected)

• No primary stroke, seizure, TBI w/in 6 mos

• Diagnostic uncertainty/discomfort

• LBD, FTD, complex mixed

• Young onset (age<65)

• Screened for ”usual suspects”

• Lipids, CBC, CMP, A1C

• B12 (maybe MMA, Homocysteine), folate, vit D

• TSH

• Sleep

• Alcohol

• If imaging, MRI with volumetric analysis

Representative Services

• Data Gathering visit

– VS- full set including weight and SpO2

– Physician evaluation

– Social work consultation

• Diagnostic tests (MRI, neuropsych, labs, LP, PET)

• Family Visit

– Physician feedback

– ARNP/Social Worker

• Managed follow up/partnership with PCP

Future Directions• GIM Integration

• MBWC-Primary Care Liaison Team

• Annual Medicare Wellness Visit

• Neighborhood Clinics

• Group interventions for MCI/early dementia

• HABIT

• Dementia-friendly Intergenerational Arts

• Exercise

• MBSR

• Outcome Measurement

• Dementia Performance Measurement Set (AAN, 2011)

Resources

• Dementia Action Collaborative/State Plan– https://www.dshs.wa.gov/altsa/stakeholders/alzheimer

s-state-plan

Resourceshttp://www.nwgwec.org/activities/geri-series/driving-dementia/

Resources

• Alzheimer Association (www.alz.org)

– Taking Action workbook:

http://www.alz.org/mnnd/documents/15_ALZ_Taking_Action

_Workbook.pdf

– Living Well workbook:

http://www.alz.org/mnnd/documents/15_ALZ_Living_Well_

Workbook_Web.pdf

• Momentia Seattle (www.momentiaseattle.org)

• Areas on Aging (http://www.agingwashington.org)

• UW MBWC (http://depts.washington.edu/mbwc/) 74

Thank you for your attention!

Questions?

Contact Information

Memory and Brain Wellness Centerhttps://depts.washington.edu/mbwc/

Harborview Medical Center

325 9th Ave., 3rd Floor West Clinic

Seattle, WA 98104

Phone 206-744-3045

Fax 206-744-8527

krhoads@uw.edu

References/Resources• Beaudreau, S. A., and O’Hara, R. (2008). Late-life anxiety and cognitive impairment: a review. Am. J. Geriatr.

Psychiatry 16, 790–803

• Benson, H., Greenwood, M. M., and Klemchuk, H. (1975). The relaxation response: psychophysiologic aspects

and clinical applications. Int. J. Psychiatry Med. 6, 87–98

• Brookmeyer, R., Johnson, E., Ziegler-Graham, K., and Arrighi, H. M. (2007). Forecasting the global burden of

Alzheimer’s disease. Alzheimers Dement. 3, 186–191

• Chien, L. Y., Chu, H., Guo, J. L., Liao, Y. M., Chang, L. I., Chen, C. H., et al. (2011). Caregiver support groups

in patients with dementia: a meta-analysis. Int. J. Geriatr. Psychiatry 26, 1089–1098.

• Chiesa, A., Calati, R., and Serretti, A. (2011). Does mindfulness training improve cognitive abilities? A

systematic review of neuropsychological findings. Clin. Psychol. Rev. 31, 449–464.

• Davidson, R.J. & McEwen, B.S. (2012) Social influences on neuroplasticity: stress and interventions to

promote well-being. Nature Neuroscience 15, 689–695

• Dopson, L. (2005). Spirituality and Alzheimer’s. Nurs. Older People 17, 39.

• Epel, E., Daubenmier, J., Moskowitz, J. T., Folkman, S., and Blackburn, E. (2009). Can meditation slow rate of

cellular aging? Cognitive stress, mindfulness, and telomeres. Ann. N. Y. Acad. Sci. 1172, 34–53.

• Forette, F., Seux, M. L., Staessen, J. A., Thijs, L., Birkenhager, W. H., Babarskiene, M. R., et al. (1998).

Prevention of dementia in randomised double-blind placebo-controlled systolic hypertension in Europe (Syst-

Eur) trial. Lancet 352, 1347–1351.

• Gauthier, S., Cummings, J., Ballard, C., Brodaty, H., Grossberg, G., Robert, P., et al. (2010). Management of

behavioral problems in Alzheimer’s disease. Int. Psychogeriatr. 22, 346–372.

• Germer, C. K., Siegel, R. D., and Fulton, P. R. (2005). Mindfulness and Psychotherapy. New York: Guilford

Press.

• Grant, J. A., Courtemanche, J., Duerden, E. G., Duncan, G. H., and Rainville, P. (2010). Cortical thickness and

pain sensitivity in Zen meditators. Emotion 10, 43–53.

• Grant, J. A., Duerden, E. G., Courtemanche, J., Cherkasova, M., Duncan, G. H., and Rainville, P. (2013).

Cortical thickness, mental absorption and meditative practice: possible implications for disorders of attention.

Biol. Psychol. 92, 275–281.

• Grossman, P., Niemann, L., Schmidt, S., and Walach, H. (2004). Mindfulness-based stress reduction and

health benefits. A meta-analysis. J. Psychosom. Res. 57, 35–43.

References/Resources• Hoge, E. A., Chen, M. M., Orr, E., Metcalf, C. A., Fischer, L. E., Pollack, M. H., et al. (2013). Loving-

Kindness Meditation practice associated with longer telomeres in women. Brain Behav. Immun. 32, 159–

163.

• Holzel, B. K., Carmody, J., Vangel, M., Congleton, C., Yerramsetti, S. M., Gard, T., et al. (2011). Mindfulness

practice leads to increases in regional brain gray matter density. Psychiatry Res. 191, 36–43.

• Holzel, B. K., Ott, U., Gard, T., Hempel, H., Weygandt, M., Morgen, K., et al. (2008). Investigation of

mindfulness meditation practitioners with voxel-based morphometry. Soc. Cogn. Affect. Neurosci. 3, 55–61.

• Horrigan, B. J. (2007). New studies support the therapeutic value of meditation. Explore (NY) 3, 449–450.

• Hulme, C., Wright, J., Crocker, T., Oluboyede, Y., and House, A. (2010). Non-pharmacological approaches

for dementia that informal carers might try or access: a systematic review. Int. J. Geriatr. Psychiatry 25,

756–763.

• Innes, K. E., Selfe, T. K., Brown, C. J., Rose, K. M., and Thompson-Heisterman, A. (2012). The effects of

meditation on perceived stress and related indices of psychological status and sympathetic activation in

persons with Alzheimer’s disease and their caregivers: a pilot study. Evid. Based Complement. Altern. Med.

2012, 927509.

• Jacobs, T. L., Epel, E. S., Lin, J., Blackburn, E. H., Wolkowitz, O. M., Bridwell, D. A., et al. (2011). Intensive

meditation training, immune cell telomerase activity, and psychological mediators.

Psychoneuroendocrinology 36, 664–681.

• Jacobs, T. L., Shaver, P. R., Epel, E. S., Zanesco, A. P., Aichele, S. R., Bridwell, D. A., et al. (2013). Self-

reported mindfulness and cortisol during a Shamatha meditation retreat. Health Psychol. 32, 1104–1109.

• Kaufman, Y., Anaki, D., Binns, M., and Freedman, M. (2007). Cognitive decline in Alzheimer disease: impact

of spirituality, religiosity, and QOL. Neurology 68, 1509–1514.

• Khalsa, D. S., Amen, D., Hanks, C., Money, N., and Newberg, A. (2009). Cerebral blood flow changes

during chanting meditation. Nucl. Med. Commun. 30, 956–961.

• Khanna, S., and Greeson, J. M. (2013). A narrative review of yoga and mindfulness as complementary

therapies for addiction. Complement. Ther. Med. 21, 244–252.

• Khatri, D., Mathur, K. C., Gahlot, S., Jain, S., and Agrawal, R. P. (2007). Effects of yoga and meditation on

clinical and biochemical parameters of metabolic syndrome. Diabetes Res. Clin. Pract. 78, e9–e10.

References/Resources• Kivipelto, M., Helkala, E. L., Laakso, M. P., Hanninen, T., Hallikainen, M., Alhainen, K., et al. (2001). Midlife

vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ 322,

1447–1451.

• Kivipelto, M., Ngandu, T., Fratiglioni, L., Viitanen, M., Kareholt, I., Winblad, B., et al. (2005). Obesity and

vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch. Neurol. 62, 1556–

1560.

• Lakhan, S. E., and Schofield, K. L. (2013). Mindfulness-based therapies in the treatment of somatization

disorders: a systematic review and meta-analysis. PLoS ONE 8:e71834.

• Lavretsky, H., Epel, E. S., Siddarth, P., Nazarian, N., Cyr, N. S., Khalsa, D. S., et al. (2013). A pilot study of

yogic meditation for family dementia caregivers with depressive symptoms: effects on mental health,

cognition, and telomerase activity. Int. J. Geriatr. Psychiatry 28, 57–65.

• Lazar, S. W., Kerr, C. E., Wasserman, R. H., Gray, J. R., Greve, D. N., Treadway, M. T., et al. (2005).

Meditation experience is associated with increased cortical thickness. Neuroreport 16, 1893–1897.

• Lindberg, D. A. (2005). Integrative review of research related to meditation, spirituality, and the elderly.

Geriatr. Nurs. 26, 372–377.

• Luders, E., Clark, K., Narr, K. L., and Toga, A. W. (2011). Enhanced brain connectivity in long-term

meditation practitioners. Neuroimage 57, 1308–1316

• Luders, E., Thompson, P. M., Kurth, F., Hong, J. Y., Phillips, O. R., Wang, Y., et al. (2013a). Global and

regional alterations of hippocampal anatomy in long-term meditation practitioners. Hum. Brain Mapp. 34,

3369–3375.

• Luders, E., Kurth, F., Toga, A. W., Narr, K. L., and Gaser, C. (2013b). Meditation effects within the

hippocampal complex revealed by voxel-based morphometry and cytoarchitectonic probabilistic mapping.

Front. Psychol. 4:398.

• Luders, E., Toga, A. W., Lepore, N., and Gaser, C. (2009). The underlying anatomical correlates of long-

term meditation: larger hippocampal and frontal volumes of gray matter. Neuroimage 45, 672–678.

• Lutz, A., Slagter, H. A., Dunne, J. D., and Davidson, R. J. (2008). Attention regulation and monitoring in

meditation. Trends Cogn. Sci. 12, 163–169.

References/Resources• Marciniak, R., Sheardova, K., Čermáková, P., Hudeček, D., Šumec, R., & Hort, J. (2014). Effect of meditation on

cognitive functions in context of aging and neurodegenerative diseases. Frontiers in Behavioral Neuroscience, 8.

• McEwen, B.S. (2006). Protective and damaging effects of stress mediators: central role of the brain. Dialogues

Clin Neurosci. 2006;8:367-381.

• Moss, A. S., Wintering, N., Roggenkamp, H., Khalsa, D. S., Waldman, M. R., Monti, D., et al. (2012). Effects of

an 8-week meditation program on mood and anxiety in patients with memory loss. J. Altern. Complement. Med.

18, 48–53.

• Newberg, A., Alavi, A., Baime, M., Pourdehnad, M., Santanna, J., and d’Aquili, E. (2001). The measurement of

regional cerebral blood flow during the complex cognitive task of meditation: a preliminary SPECT study.

Psychiatry Res. 106, 113–122.

• Newberg, A. B., Serruya, M., Wintering, N., Moss, A. S., Reibel, D., and Monti, D. A. (2013). Meditation and

neurodegenerative diseases. Ann. N. Y. Acad. Sci. 1307, 112–123.

• Newberg, A. B., Wintering, N., Khalsa, D. S., Roggenkamp, H., and Waldman, M. R. (2010a). Meditation effects

on cognitive function and cerebral blood flow in subjects with memory loss: a preliminary study. J. Alzheimers Dis.

20, 517–526.

• Newberg, A. B., Wintering, N., Waldman, M. R., Amen, D., Khalsa, D. S., and Alavi, A. (2010b). Cerebral blood

flow differences between long-term meditators and non-meditators. Conscious. Cogn. 19, 899–905.

• Olazaran, J., Reisberg, B., Clare, L., Cruz, I., Pena-Casanova, J., Del Ser, T., et al. (2010). Nonpharmacological

therapies in Alzheimer’s disease: a systematic review of efficacy. Dement. Geriatr. Cogn. Disord. 30, 161–178.

• Pagnoni, G., and Cekic, M. (2007). Age effects on gray matter volume and attentional performance in Zen

meditation. Neurobiol. Aging 28, 1623–1627.

• Prakash, R., Rastogi, P., Dubey, I., Abhishek, P., Chaudhury, S., and Small, B. J. (2012). Long-term concentrative

meditation and cognitive performance among older adults. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn.

19, 479–494

• Prince, M., Bryce, R., Albanese, E., Wimo, A., Ribeiro, W., and Ferri, C. P. (2013). The global prevalence of

dementia: a systematic review and metaanalysis. Alzheimers Dement. 9, 63e–75e.

References/Resources• Reitz, C. (2013). Dyslipidemia and the risk of Alzheimer’s disease. Curr. Atheroscler. Rep. 15, 307.

• Rocca, W. A., Petersen, R. C., Knopman, D. S., Hebert, L. E., Evans, D. A., Hall, K. S., et al. (2011). Trends in

the incidence and prevalence of Alzheimer’s disease, dementia, and cognitive impairment in the United States.

Alzheimers Dement. 7, 80–93.

• Roher, A. E., Debbins, J. P., Malek-Ahmadi, M., Chen, K., Pipe, J. G., Maze, S., et al. (2012). Cerebral blood

flow in Alzheimer’s disease. Vasc. Health Risk Manag. 8, 599–611.

• Salthouse, T. A. (2011). Neuroanatomical substrates of age-related cognitive decline. Psychol. Bull. 137, 753.

• Schwartz, G. E., Davidson, R. J., and Goleman, D. J. (1978). Patterning of cognitive and somatic processes in

the self-regulation of anxiety: effects of meditation versus exercise. Psychosom. Med. 40, 321–328.

• Tang, Y. Y., Lu, Q., Geng, X., Stein, E. A., Yang, Y., and Posner, M. I. (2010). Short-term meditation induces

white matter changes in the anterior cingulate. Proc. Natl. Acad. Sci. U.S.A. 107, 15649–15652.

• Vestergaard-Poulsen, P., van Beek, M., Skewes, J., Bjarkam, C. R., Stubberup, M., Bertelsen, J., et al. (2009).

Long-term meditation is associated with increased gray matter density in the brain stem. Neuroreport 20, 170–

174.

• Wachholtz, A. B., and Pargament, K. I. (2005). Is spirituality a critical ingredient of meditation? Comparing the

effects of spiritual meditation, secular meditation, and relaxation on spiritual, psychological, cardiac, and pain

outcomes. J. Behav. Med. 28, 369–384.

• Waelde, L. C., Thompson, L., and Gallagher-Thompson, D. (2004). A pilot study of a yoga and meditation

intervention for dementia caregiver stress. J. Clin. Psychol. 60, 677–687.

• Walton, K. G., Schneider, R. H., and Nidich, S. (2004). Review of controlled research on the transcendental

meditation program and cardiovascular disease. Risk factors, morbidity, and mortality. Cardiol. Rev. 12, 262–

266.

• Wang, D. J., Rao, H., Korczykowski, M., Wintering, N., Pluta, J., Khalsa, D. S., et al. (2011). Cerebral blood

flow changes associated with different meditation practices and perceived depth of meditation. Psychiatry Res.

191, 60–67.

• Wells RE1, Yeh GY, Kerr CE, Wolkin J, Davis RB, Tan Y, Spaeth R, Wall RB, Walsh J, Kaptchuk TJ, Press D,

Phillips RS, Kong J. Meditation's impact on default mode network and hippocampus in mild cognitive

impairment: a pilot study. Neurosci Lett. 2013 Nov 27;556:15-9.

• Xiong, G. L., and Doraiswamy, P. M. (2009). Does meditation enhance cognition and brain plasticity? Ann. N. Y.

Acad. Sci. 1172, 63–69.