Next Step in Anti-aging Innovation - Naresuan University

Next Step in Anti-aging Innovation

“Moral technology, Inner Power, Together We Can”

18-19 January 2017

Faculty of Medicine, Naresuan University

Prof. Luiza Spiru, MD, PhD

Professor of Geriatrics and Old Age Psychiatry

Bucharest "Carol Davila" University of Medicine and Pharmacy

Head, Dept. of Geriatrics Gerontology and Psychogeriatrics

President of Ana Aslan International Foundation

Perspective: Our commanding oversight directed towards the future allows predictive analysis of each step

in the development and progress of the organization without ever forgetting its goal, the human being.

Respect: We assume the vocation of opinion leaders thus considering mutual respect as the basis of any

relationship between patients, staff and team members.

Individuality: Our methods are tailored and customized to each new challenge because only respecting the

individuality can we build a system always ready to adopt bold, unique, original solution.

Dedication: Commitment to organizational values and passion for what we do allow us to transfer our

knowledge and expertise in developing avant-garde health services in the field of brain aging.

Excellence: In everything we do.

AAIFF mission is to

integrate scientific progress into the original, holistic concept of

predictive, preventive and personalized medicine in order to give patients,

medical and scientific community the instruments to make brain aging medicine the longevity medicine.

AAIFF vision is to

convert the latest achievements of medical science in the Art of Aging.

All rights reserved. No part of these slides can be reproduced, stocked or transmitted in no other form and through no other electronic,mechanic, or photocopy way, without the approval of “Ana Aslan” International Academy of Aging®© “Ana Aslan” InternationalFoundation ®© Brain Aging International Journal ®©.

Our Philosophy

Actual Research Outcomes at AAIF

1. A holistic - integrative, ‘omics’-based research paradigm - CRITICAL NEUROMES in COGNITIVE

AGING and PATHOLOGY:

Main objective: personalized evaluation of susceptibility to develop non

familial (sporadic) Alzheimer’s Disease (AD)

Envisaged direct outcomes:

Improvement of scientific knowledge regarding AD pathophysiology

New insights for personalized preventive and therapeutic algorithms

2. A complex, omics-based Evaluation Protocol

- component panels: clinical, psychometric, metabolic, genomic-epigenomic,

methylomic, nutriomic and sociomic

3. Active promotion of Prediction, Prevention and Personalization values in several EU funded projects:

• EADC (European Alzheimer’s Disease Consortium) QLK6-CT-2001-30003 http://eadc.alzheimer-

europe.org

• DESCRIPA (Development of screening guidelines and diagnostic criteria for predementia

Alzheimer’s disease) QLK6-CT-2002-02645

• ICTUS (Impact of Cholinergic Treatment Use) QLK6 CT 2002 02455


http://eadc.alzheimer-europe.org/

3PM Educational Initiative in Brain Aging

The BRAINAGING Educational Strategic National Project

(FP7-SOP-HRD 81/3.2/S/46975); a 5 milion euros grant“Training in the new medical technologies for the specialist physicians and

medical assistants acting in hospitals and ambulatories in the field of brain

aging”

Running area - national level

Running time – 2010-2013

Main objectives:

• To create an Integrated Syllabus and Curricula in the 3P M of Brain Aging for 7 different

medical specialties

• Training of 1.420 doctors and 1.600 medical assistants specialized in -neurology-

neurosurgery, anesthesiology, psychiatry, geriatrics, laboratory and molecular medicine

and family medicine in the 3PM-based approach of brain aging

• Building a national network of trained specialists/dedicated centers

• Promotion of a dedicated eHealth and eLearning platform


Chapter 1

The Real Value Early Diagnosis adds for the patients with neurodegenerative diseases


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Neurodegenerative Diseases - A Growing Challenge Remarkable initiatives Is early detection of neurodegenerative pathology a critical step? Is the impact of a diagnosis disclosure a critical point? The right to a diagnosis ‘Making the diagnosis well’ Would early identification and intervention lead to positive individual

outcomes? May early diagnosis and intervention offer large social benefits? May early diagnosis and intervention offer large financial benefits? Have we powerful means for early diagnosis at hand? Have we a clear picture of to do’s? Is early detection publicly recognized as critical? Conclusions

SUMMARY


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More than 600 disorders afflict the nervous system.

Neurodegenerative diseases are complex, multifactorial pathological entities that require multifactorial approach.

Despite the remarkable scientific and technological progress,actually no cure is available.

Neurodegenerative Diseases - A Growing Challenge

Miksys SL, Tyndale RF, 2010. Neurodegenerative Diseases: A Growing Challenge. Clinical Pharmacology & Therapeutics 88, 427-430


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Harvard NeuroDiscovery Center statistics:

Today,

5 million sufferers from Alzheimer's disease;

1 million from Parkinson's;

400,000 from multiple sclerosis (MS);

30,000 from amyotrophic lateral sclerosis (ALS)

30,000 from Huntington's disease.

Without new, powerful interventional means in 2040 more than 12 million Americans will suffer from neurodegenerative diseases.

Harvard NeuroDiscovery Center. The challenge of neurodegenerative diseases .


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Parkinson’s disease statistics (Australia):

30 more people are diagnosed with Parkinson’s each day;

Parkinson’s cases were growing by 17% over the last six years;

20% of PD sufferers are of working age

costs have grown by over 48%;

the estimated burden of the disease for 2011-12 $7.6 billion

Parkinson’s people costs out of their own pockets about $12,000 yearly

2011 Report on Parkinson’s Disease in Australia, http://parkinsonssa.wordpress.com/2011/10/24/2011-report-on-parkinson%E2%80%99s-disease-in-australia/

Dementia in the Asia Pacific Region

Key findings:

The number of people living with dementia in the Asia Pacific region will triple

between now and 2050

By the middle of the century, more than half of the total number of people

with dementia worldwide will live in the Asia Pacific region

Dementia care costs in the region currently stand at US$185 billion, with 70% of

this amount occurring in the advanced economies

These figures are likely to increase as the numbers of people with dementia

grow, burdening the health systems of countries in the region, especially those

in low and middle income nations

2014 ADI (Alzheimer’s Disease International) Report on Dementia in the Asia Pacific Region;https://www.alz.co.uk/adi/pdf/Dementia-Asia-Pacific-2014.pdf

Four major challenges are outlined in the report:

1. the limited awareness of dementia

2. the false perception that dementia is a natural part of

ageing

3. inadequate human and financial resources to meet the

care needs of people with dementia

4. inadequate training for professional carer’s



alzheimer’s Disease international rePort 201460

BackgroundThe Alzheimer’s Disease and Related Disorders Association-Thailand (ARDA-T)

represents people with dementia and their caregivers at a national level.

ARDA-T was founded in July 1996 by a group of healthcare professionals and the

family members of a person with dementia. It was first established as an informal

group of people with a common interest, becoming a legal association in November

1998.

Since then ARDA-T has become stronger by recruiting a network of organisations

throughout Thailand. Currently there is one main organisation located in Bangkok with

other networks in northern, north eastern and southern parts of Thailand. Each network

works independently

to provide support, information, education programmes and services to their local

communities. The organisation has one employed staff member. The rest of the staff

and committees are volunteers.

Number of people supportedARDA-T does not yet have a national mechanism to collect data on the number

or type of people that the main organisation and networks provide service to.

National dementia strategy/planThailand does not have a national dementia strategy/ plan. The aim is to start work to

address this gap in 2014. The work through local communities has helped people with

dementia and their caregivers to maximise their independence and wellbeing by

reducing stigma and providing clear, comprehensive information and an integrated,

holistic approach to dementia care and

support. However, with the current political instability and without a national dementia

strategy/plan, it is impossible to develop clear, consistent, well-resourced and easily

accessible dementia care pathways.

Awareness raisingRaising public awareness is one of ARDA-T’s strategic plans since the

establishment of the association. On an ongoing basis, awareness raising activities

include:

• Media engagement – proactively pitching media stories about the work of ARDA-T

and its Members, publicising local and international research etc., and being part of

national discussions about dementia related topics

• Publications – publishing and promoting knowledge booklets, a quarterly newsletter

and an annual report

• Online – active engagement via our website

• Events - running events such as World Alzheimer’s Month, an annual conference,

and participating in other events within the sector

• Stakeholder engagement – engaging with the wider dementia, health and social

services communities to position the association as the leading organisation

representing people affected by dementia in Thailand.

ResourcesThe current suite of information resources includes brochures and booklets that cover a

number of topics such as being a caregiver for people with dementia, Alzheimer’s

disease knowledge, healthy brain techniques etc. These are readily available on the

website and in hard copy through the Members.

The website www.azthai.org is an important hub of information for people affected by

dementia and for stakeholders. It contains information resources, dementia related

news and research as well as information and news about ARDA-T and Members’

activities. ARDA-T also provides and promotes international research and resources

including the World Alzheimer Reports and the Global Dementia Charter.

TrainingARDA-T has had significant input into the training of the healthcare workforce in

Thailand. It usually has two types of training workshops/conferences annually. One

is for healthcare professionals and the other for family caregivers.

ServicesARDA-T provides public services by holding monthly support group sessions for

caregivers and family members of people with dementia. The hotline phone numbers

are available to ensure access to anyone who requires support for people with

dementia urgently.

A number of networks have initiated specialised programs within their local area to

provide stimulating, meaningful and culturally appropriate activities for people with

dementia, and respite for their caregivers.

Annex R: THAILANDEstimated Number of People with Dementia (‘000) Estimated Costs of Dementia in Y2015 US$ (mil)

Y2015 Y2030 Y2050 Medical Non-Medical Informal Care Total

600 1,117 2,077 $ 89 $ 721 $ 854 $ 1,664

(data from ADI 10/66 Dementia Research Group)

Country Profile contributed by

alzheimer’s Disease and related Disorders association-thailand (www.azthai.org)

http://www.azthai.org/


Recommendations:

The report recommends that countries in the region should:

Provide education and awareness

Improve the quality of life of people living with dementia through public

awareness and training programs

Promote the development of health and community care systems to deal with

an increasing number of people with the disease

Raise awareness of risk reduction strategies

Develop national dementia action plans

Promote and support further research into the health and care systems in lower

and middle income countries in the development of health policy



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In Europe:

Amongst neurodegenerative disorders, the dementias are responsible for

the greatest burden.

7 million people have Alzheimer’s disease and related disorders

This figure is expected to double every 20 years as the population ages.

Dementia care currently costs approximately €130 billion per annum

European Brain Council Report-2011

Eur Neuropsychopharmacol. 2011; 21(10):718-79 (ISSN: 1873-7862)

Gustavsson A ; Svensson M ; Jacobi F ; Allgulander C ; Alonso J ; Beghi E ; Dodel R ; Ekman M ; Faravelli C ; Fratiglioni L ; Gannon B ; Jones DH ; Jennum P ; Jordanova A ; Jönsson L ; Karampampa K ; Knapp M ; Kobelt G ; Kurth T ; Lieb R ; Linde M ; Ljungcrantz C ; Maercker A ; Melin B ; Moscarelli M ; Musayev A ; Norwood F ; Preisig M ; Pugliatti M ; Rehm J ; Salvador-Carulla L ; Schlehofer B ; Simon R ; Steinhausen HC ; Stovner LJ ; Vallat JM ; den Bergh PV ; van Os J ; Vos P ; Xu W ; Wittchen HU ; Jönsson B ; Olesen J ; OptumInsight, Stockholm, Sweden

The first 4 Brain Diseases affecting the European Population-over 55 y

①Anxiety-Depression,

②Neurodegenerative –Diseases

③Alcoholism

④Stroke


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February 7th, 2012

the EU Joint Programme in Neurodegenerative Disease Research(JPND) launched the European-wide strategy to tackleneurodegenerative diseases (especially Alzheimer ’ s andParkinson’s).

Main goals:To develop new therapeutic and preventive strategiesTo improve health and social care approachesTo raise awareness and de-stigmatize Alzheimer’s and otherneurodegenerative disordersTo alleviate the economic and social burden of these diseases.

First European-wide research strategy to tackleAlzheimer’s and other Neurodegenerative Diseases,7 February 2012. http://www.neurodegenerationresearch.eu/initiatives/strategic-research-agenda/

Remarkable initiatives


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The European-wide strategy agenda for neurodegenerative diseasesincludes two goals of increasing urgency:

to find radically improved predictive, preventive personalized interventional means

To promote early detection as the first, crucial step



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Is early detection of neurodegenerative pathology a critical step?

YES, it is !

Arguments

Lack of detection a significant barrier

Three-quarters of the estimated 36 million dementia people worldwide have not been diagnosed and cannot benefit from treatment, information and care.

In high income countries, only 20-50% of dementia cases are recognized and documented in primary care.

In low- and middle-income countries, this proportion could be as low as 10%.

The World Alzheimer's Report 2011: The benefits of early diagnosis and intervention


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Arguments

Failure to diagnose often results from false beliefs: dementia is a normal part of aging, nothing can be done to help.

Dementia diagnosis provides access to evidence-basedtreatment, care, and support across the disease course

The World Alzheimer's Report 2011 interventions can make adifference, even in the early stages of the illness.

Drugs and psychological interventions for early-stage dementiacan improve cognition, independence, and quality of life.

The World Alzheimer's Report 2011: The benefits of early diagnosis and intervention)

1. Natural History

2. Amnestic Episodic Cognitive Decline -Amnestic MCI

• Executive Function (working memory, motor visual-spatial function, verbal

fluency)

• visual-spatial abilities

3. Neuropsychological Clinical tools

4. Imaging- Hippocampus Atrophy, decreased Parietal-Temporal Glucose

metabolism, WML

1. MRI-Structural and Functional

2. SPECT/PET

5. CSF ( increased tau, p-tau, decreased -β42amyloid

6. Apo E4-genetic Familial mutation

Have we powerful means for early diagnosis?


E, Monastero R, Mecocci P. Mild cognitive impairment: a systematic review. J Alzheimers Dis 2007; 12(1):23-35.

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Have we powerful means for early diagnosis at hand?

The pathological brain changes eventually leading to symptoms evolve well in advance: 20-30 years prior to AD symptoms the time course and pattern of cerebrovascular pathology is much more variable.

The prodromal phase definition requires cognitive impairment not meeting dementia diagnostic criteria (no impairment in core ADLs).

Conversion rates to dementia are highest for the amnestic form of MCI (ranging between 10-15% per year in clinic-based studies and 5-10% in longitudinal population-based studies) (Mariani et al, 2007)

Conversion is by no means inevitable, for MCI up to a quarter in some studies show

subsequent recovery of normal cognitive function (Mariani et al, 2007).


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Is the impact of a diagnosis disclosure a critical point ?

YES, it is !

Despite a general consensus that dementia should be diagnosed as early as possible, there is considerable debate whether:

such diagnosis may potentially cause severe anxiety and depression

this information will be beneficial to patients and families as long as no treatment is available ?

Alzheimer’s Disease Neuroimaging Initiative (ADNI) reported that a thinning of the brains cortex in cognitively normal adults, as shown on MRI, appeared to be predictive of the disease

During the follow-up period, 72 patients (53.7%) developed Alzheimer’s disease. twenty-one patients (15.7%) developed other forms of dementia.

Patients who had normal values of the biomarkers did not have a higher risk of developing AD, even though they had mild cognitive impairment.

A baseline Aβ42/P-tau ratio predicted the development of AD within 9.2 years

The sensitivity of that ratio - 88%,

the specificity 90%,

the positive predictive value was 91%,

and the negative predictive value was 86%

CSF Abnormalities: Early Precursors of Alzheimer’s

Arch Gen Psychiatry. 2012;69(1):98-106http://www.medscape.com/viewarticle/756633_print

Dubois et al, Lancet Neurol, 2007

Cognitive Decline Can Start at Age 45

the longitudinal Whitehall II cohort study, participants aged 45 to 70 years at baseline using 3 cognitive assessments over a period of 10 years

cognitive scores declined in memory, reasoning, phonemic and semantic fluency, except vocabulary

Over the 10-year study period, there was also a -3.6% decline in mental reasoning in men aged 45 to 49 years and a -9.6% decline in those aged 65 to 70 years. The corresponding figures for women were -3.6% and -7.4%

the cognitive decline demonstrates the importance of promoting healthy lifestyles, particularly cardiovascular health

there is emerging evidence that "what is good for our hearts is also good for our heads.”

targeting patients who suffer from one or more risk factors for heart disease (obesity, high blood pressure, and high cholesterol levels)

Determining a new Age Window potential intervention for early Dementia

BMJ. 2011;343. Published online January 5, 2012. Archana-Singh Manon et all

De LJ et al., 2008. The primary care diagnosis of dementia in Europe: an analysis using multidisciplinary,multinational expert groups. Aging Ment Health 12(5):568-576. 28

The early diagnosis can finally facilitate suitable, complex, personalized interventions according to the individual risk factors - vascular , anxiety-depression…

• Pharmacological

• Potentially disease modifying

• Hormone replacement

• Micronutrition

• Antihypertensive therapy

• Antiinflammatory drugs etc.

• Symptomatic

• Acetylcholinesterase inhibitors

• Memantine

• COMBO therapy

• Antidepressants etc.


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Non-pharmacological

For patient benefit

Strategies to support and enhance cognition

Psychological and behavioral therapies

Nutritional therapy (strongly argued and documented)

Stress management

Legal and financial advice

Support groups

Physical exercise

Individual counseling

Psychological interventions

Education and training

Brain Food: Fending Off Mental and Neurologic Illness With Diet


Weimer DL, Sager MA, 2009. Early identification and treatment of Alzheimer'sdisease: social and fiscal outcomes. Alzheimers Dement. 5(3):215-26

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Would early identification and intervention lead to positiveindividual outcomes ?

Real Opportunities-

access available to drug and non-drug therapies improve their cognition enhance their quality of life have the power to plan their own healthcare and future


May early diagnosis and intervention offer large social benefits ?

YES, it may !

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"There are many physical, emotional and social benefits of early detection, diagnosis and intervention for people with Alzheimer's and their caregivers"

"Early detection empowers people with the disease to participate in decisions about their treatment and future care, as well as consider clinical trial opportunities.”

Being diagnosed early is vital to receiving the best help and care possible, able to: delay disease progression and the alteration of life quality

Bluethmann SM, 2012 . The Gothenburg Senior Center, 2012. Early detection of Alzheimer’s critical. Gothenburg Times, 14:39 – 41)


Sakai J, 2009. Early Alzheimer's diagnosis offers large social, fiscal benefits. University of Wisconsin News, retrieved onlineon 0.03.2012 at http://www.news.wisc.edu/16716; Weimer DL, Sager MA, 2009. Early identification and treatment ofAlzheimer's disease: social and fiscal outcomes. Alzheimers Dement. 5(3):215-26

May early diagnosis and intervention offer large fiscal benefits?

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Patients with neurodegenerative diseases are heavy users of long-term careservices estimated annual costs in USA: tens of billions of dollars (Sakai J, 2009).

Early diagnosis and treatment of dementias could save billions of dollars whilesimultaneously improving care (Weimer DL, Sager MA, 2009)

"The future of this disease is to intervene decades before someone becomessymptomatic.” (Weimer & Sager, 2009)

The issue is becoming more pressing as the population ages (e.g. estimates of ADincidence in the U.S by 2050 is of 1 million cases)


The World Alzheimer's Report 2011; The 2011 Report on Parkinson ’ s Disease in Australia,http://parkinsonssa.wordpress.com/2011/10/24/2011-report-on-parkinson%E2%80%99s-disease-in-australia;Merck Annual Report on Neurodegenerative Diseases 2011, http://merck.online-report.eu/2010/ar/merckserono/therapeuticareas/neurodegenerativediseases.html

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Have we a clear picture of to do’s ?

Recommendations issued by worldwide analytical reports (TheWorld Alzheimer's Report 2011, The 2011 Report on Parkinson’s Diseasein Australia, Merck Annual Report on Neurodegenerative Diseases 2011etc.) :

Every country should have a national strategy able to:

promote early diagnosis and intervention ,

raise awareness,

train the health and social care workforce,

strengthen the health system.


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All primary care services should have basic competency in:

early detection of dementia,

making and imparting a provisional dementia diagnosis

initial management of dementia.

Networks of specialist diagnostic centres should be established to:

confirm early stage dementia diagnoses

formulate care management plans.


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2010-20133000 specialists

Initiator- Prof. Luiza Spiru MD, PhD

• early diagnosis

• monitoring and treatment, personalized interventions and preventive tools in the field of brain aging and memory impairment diseases

• elaborating the guidelines for the early diagnosis in neurodegenerative diseases according to the European and international definitions

• developing the new research criteria in preventive clinical trials in brain aging

• professional training in the field of early diagnosis of brain aging for GPS, geriatricians, neurologists, psychiatrists, psychologists, social assistants, home care assistants

The Brain Aging Educational Integrated Project - adapting the principles of 3P Medicine in Romania


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The Gothenburg Senior Center, 2012. Early detection of Alzheimer’s critical. Gothenburg Times, 14:39 – 41)

Is early detection publicly recognized as critical ?

YES, it is !

In 2008, Alzheimer’s Association education campaign “Early Detection Matters”was selected as the winner in the American Express Members Project competition.

American Express awarded $1.5 million for supporting this campaign.


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The main pillars of “Early Detection Matters” education campaign

To make people aware that memory loss that disrupts everyday life is not a typical part of aging.

To make people aware that late diagnostic throws down the opportunities

to fully participate in decisions about treatment and care,

to make key decisions about treatment,

to fully benefit from treatment and care

to adapt activities to promote existing skills and interests

to identify social and community resources to support

independence as long as possible.

to make a fully rational planning of the future


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To make people aware about the warning signs of a possible neurodegenerative disease

1. Memory loss that disrupts daily life (typical: forgetting names or appointments, but remembering them later)

2. Challenges in planning or solving problems (typical: making occasional errors when balancing a checkbook )

3. Difficulty completing familiar tasks at home, at work or at leisure (typical: occasionally needing help to use the settings on a microwave)

4. Confusion with time or place (typical: getting confused about the day but figuring it out later)

5. Trouble understanding visual images and spatial relationships(typical: pass a mirror and think someone else is in the room )


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6. New problems with words in speaking or writing (typical: Sometimes having trouble finding the right word)

7. Misplacing things and losing the ability to retrace steps(typical: Misplacing a pair of glasses or the remote control)

8. Decreased or poor judgment (typical: Making a bad decision once in a while)

9. Withdrawal from work or social activities (typical: Sometimes feeling weary of work, family and social obligations)

10. Changes in mood and personality (typical: very specific ways of doing things and becoming irritable when a routine is disrupted)


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The 21st Century is widely recognized as the era of neurodegenerative diseases

Alzheimer’s and related disorders must be addressed as a global health challenge

To promote early diagnosis as a crucial step

To support research for improved therapeutic and preventive means

To promote an ethical debate and approach

To develop training for specific care workforce

To provide information and awareness among the general public

CONCLUSIONS


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The right to a diagnosis

The Alzheimer’s Disease Bill of Rights (1995):

Every person diagnosed with Alzheimer’s disease or other neurodegenerativedisorder deserves to be informed of one’s diagnosis (Black JS, 1995)

Patient advocacy groups:

“Except in unusual circumstances, physicians and the care team should disclosethe diagnosis to the individual because of the individual’s moral and legal rightto know”. (Alzheimer’s Association , accessed 2012)

Post SG, Whitehouse PJ, 1995. Fairhill guidelines on ethics of the care of people with Alzheimer’s disease: a clinical summary. J Am Geriatr Soc,43(12):1423-1429; Black JS, 1995. Telling the truth: Should persons with Alzheimer’s disease be told their diagnosis? Alzheimer’s DiseaseInternational Global Perspective 1995, 6:10-11; Alzheimer’s Association website. Diagnostic disclosure, http://www. alz.org/professionals_and_researchers_diagnostic_disclosure.asp

CONCLUSIONS

Chapter 2

The causative role of Stress in AD and mild cognitive impairment (MCI)


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Stress – definition, type of stressors Stress and the bio-psychosocial model of illness onset Growing evidence for stress as a risk factor in Mild Cognitive

Impairment and Alzheimer’s disease Our pilot study Neurodegenerative diseases between bad and beneficial stress Hormesis revolution Conclusions

SUMMARY


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Stress evaluation andmanagement in dementiabecomes more and moreimportant from etiologicaland interventional viewpoint.

Neurodegenerative Diseases multifactorial etiology


Stress any endogenous or exogenous signal whose action exceeds the capacity of the organism to adapt to it


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Mastroeni D et al., 2011. Epigenetic mechanisms in Alzheimer’s disease. Neurobiology of Aging, 32:1161–1180; F Borrell-Carrió et al., 2004. The Biopsychosocial Model 25 Years Later: Principles, Practice, and Scientific Inquiry. Annals of Family Medicine 2:576-582

Illness results from the interplay between aggressive environmental factors and the inner susceptibility of the organism to that illness.

In the light of newly acquired molecular understandings, it seems that illness basically results from the bad functioning of genes chronically facing aggressive environmental demands.

inner, individual predisposing factors

(old age, certain genetic polymorphisms, oxidative stress, vitamin deficiencies,

inflammation, immune, endocrine, vascular And metabolic conditions, depression,

tumors, gender, level of education)

susceptibility to disease development

environmental risk factors(head trauma, certain infections,smoking and chemical exposure, bad stress management)

subtle, cumulative alterations

The Bio-Psycho-Social model


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Inner and outer stress


Outer challenges:

chemicals, pharmaceuticals, smoking, caffeine and drugs abuse, nutrition, sedentary lifestyle, head trauma, social (familial, professional, relational,

economical) challenges, infectious agents, etc.

Inner challenges:

Aging process, Inherited patterns of gene

functioning leading to susceptibility to disease(s)

Endogenous oxidative stress, Endogenous methylomic stress, Glycation cascade, Cortisolic cascade, etc.


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Knowledge about the role non-genetic, modifiable factors in dementia evolved more slowly than that about the genetic ones

Main research challenges:

methodological problems produced conflicting results The highly complex interactions between different

environmental factors acting on the organism

Permanently growing knowledge says YES !

May the aggressive environmental challenges (stress) have a role in cognitive decline and development of dementia ?

McCullagh CD et al., 2001. Risk factors for dementiaAdvances in Psychiatric Treatment (2001), vol. 7, pp. 24–31


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Main facts pleading for the impact of environmental stress in the late-onset Alzheimer’s disease (AD) development:

monozygotic twin concordance rates only 40% various ethnic groups in similar environments comparable

prevalence rates Apolipoprotein E (ApoE) status the main modulator of the

influence of several environmental risk factors



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Inflammatory stress

Anti-inflammatory drugs may delay nerve cells damage

The intake of non-steroidal anti-inflammatory drugs (NSAIDs) negatively associated with the risk of developing AD

AD patients may receive less NSAIDs because they lesser complain of pain.

COX-2 inhibition may favorably affect neuronal function as well as inflammation.

Clinical trials involving selective COX-2 inhibitors in Alzheimer’s disease are underway.

Trepanier CH, Milgram NW, 2010. Neuroinflammation in Alzheimer's disease: are NSAIDs andselective COX-2 inhibitors the next line of therapy? J Alzheimers Dis. 21(4):1089-99; Beard CM etal., 1998. Nonsteroidal anti-inflammatory drug use and Alzheimer’s disease: a case–controlstudy in Rochester, Minnesota, 1980 through 1984. Mayo Clinic Proceedings, 73, 951–955


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Oxidative stress

One of the most complex components of neurodegenerative processes

Amyloid beta-peptide (1-42)-induces oxidative stress, neurotoxicity and neurodegeneration in Alzheimer's disease brains

Apolipoprotein E modulates Alzheimer's Abeta(1-42)-induced oxidative damage

Therapeutic efforts aime at removing radical oxygen species (ROS) or prevent their formation in AD.

Gella A, Bolea I, 2012. Alzheimer’s Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets. Chap.15: Oxidative Stress in Alzheimer’s Disease: Pathogenesis, Biomarkers and Therapy. Suzanne De La Monte ed., 2011, pp.319-344, retrieved online at http://www.intechopen.com/books/alzheimer-s-disease-pathogenesis-core-concepts-shifting-paradigms-and-therapeutic-targets/oxidative-stress-in-alzheimer-s-disease-pathogenesis-biomarkers-and-therapy; ButterfieldDA, 2002. Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration inAlzheimer's disease brain. A review. Free Radic Res. 36(12):1307-1313; Apolipoprotein E modulates Alzheimer's Abeta(1-42)-induced oxidative damage to synaptosomes in an allele-specific manner. Lauderback CM et al, 2002. Brain Res, 924(1):90-97

http://www.ncbi.nlm.nih.gov/pubmed/12607822


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Methylomic stress

The importance of epigenetics in psychiatry is actually exploding

DNA (genes) methylation is one of the most important mechanisms bywhich genes adapt their expression to environmental demands

Evaluation and monitoring of endogenous methylation processes (theSAM-SAH + Folates + Vit B12 cycles) are of high importance in preventionand management of neurodegenerative processes

Deficiency of S-adenosyl methionine (SAM), the major methyl donor, innormal aging and in AD was documented and SAM-SAH ratio inneurodegenerative diseases is under study.

Stahl SM, 2009. Epigenetics and metabolomics in psychiatry. J.Clin.Psychiat., 70(9):1204-1205; Morrison LD1996.. Brain S-adenosylmethionine levels are severely decreased in Alzheimer's disease. J Neurochem. 67:1328-1331; Mattson MM, Shea TB, 2003. Folate and Homocysteine in Neural Plasticity and NeurodegenerativeDisorders. Trends in Neurosciences, 26:137-146; Kennedy BP et al, 2004. Elevated S-adenosylhomocysteine inAlzheimer brain: influence on methyltransferases and cognitive function. J Neural Transm. 111:547-567


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Nutrition

One of the most important signals, or stressors, from our milieu

(And one of the valuable interventional means in neurodegenerative pathology we actually have)

E.g., in the Rotterdam incident analysis (Kalmijn et al, 1997) fish consumption (source of Ω-3 polyunsaturated fatty acids) was inversely correlated with dementia (particularly AD)

However, compared with other risk factors, relatively little is known about how social engagement or diet may affect Alzheimer’s risk.

2012 Alzheimer’s Disease Facts and Figures, retrieved online on 07.04.2012 at http://www.alz.org/downloads/facts_figures_2012.pdf; Kalmijn S et al., 1997. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Annals of Neurology, 42, 776–782;

Social determinants of dementia

Social determinants the factors that determine the health of populations and individuals.

Protective factors education, income, community connectionsRisk factors eg. past trauma, poor/no education, dislocation

Lindsey J et al (1997):

“There is a belief that the ‘self’ (personhood) is gradually lost in dementia, and behaviour is a response to brain death. This leads to a ‘social death’ whereby people are treated as if they are not there, and their life history, feelings and needs do not matter”

Lindsay J et al, 1997. The Canadian Study of Health and Aging – Risk Factors for Vascular Dementia. Stroke, 28, 526–530


56

Education

Poor education a risk factor for Alzheimer’s disease, especially in males (Ott et al, 1999).

Better education greater cognitive capacity and reserve

Are childhood education or the life-time knowledge acquisition (challenging occupations) protective? still unclear!

2012 Alzheimer’s Disease Facts and Figures, retrieved online on 07.04.2012 at http://www.alz.org/downloads/facts_figures_2012.pdf; Ott A et al, 1997. Atrial fibrillation and dementia in a population-based study: the Rotterdam Study. Stroke, 28, 316–321.


57

Chemical exposure

Solvents and heavy metals possible etiological factors in neurodegeneration

High levels of iron free radical formation oxidative stress (“brain rust”)

relationship between AD and aluminium difficult to assess (large scale prospective studies needed)

the role of aluminium compounds in antacids and antiperspirants have generally yielded negative results



58

Occupational exposure

The Canadian Study of Health and Aging (Lindsay et al, 1997) an elevated oddsratio for VaD in persons who had occupational exposure to:

• pesticides, • fertilizers, • liquid plastics • rubbers.

Alcohol excess

Several studies increased risk of VaD in patients with a history of alcohol misuse (Lindsay et al, 1997),

Other studies do not confirm this (Meyer et al, 1988). Further studies are needed, as it is a potentially preventable risk..

Lindsay J et al, 1997. The Canadian Study of Health and Aging – Risk Factors for Vascular Dementia. Stroke, 28, 526–530; Meyer JS, 1986. Improved cognition after control of risk factors for multi-infarct dementia. Journal of the American Medical Association, 256, 2203–220


59

Smoking

increased risk of Alzheimer’s disease for current and former smokers (Launer et al, 1999)

Smoking has been shown to be a risk factor (Meyer et al, 1988),

The Canadian Study of Health and Aging (Lindsay et al, 1997) noAssociation (a possible explanation: the decreased survival of smokers).

Lindsay J et al, 1997. The Canadian Study of Health and Aging – Risk Factors for VascularDementia. Stroke, 28, 526–530; Meyer JS, 1986. Improved cognition after control of riskfactors for multi-infarct dementia. Journal of the American Medical Association, 256, 2203–220


60

Head trauma

The dementia pugilistica pathological changes similar to those of AD.

The hypothesis that previous head injury may increase the risk of developing AD not confirmed by Launer et al (1999) metaanalysis

The APOE-e4 carriers with moderate or severe head injury are at higher risk of developing AD

Additional research needed to better understand the impact of brain injury on AD development.

WEIDONG Zhou W et al, 2008. Meta-Analysis of APOE4 Allele and Outcome after TraumaticBrain Injury. JOURNAL OF NEUROTRAUMA 25:279–290 ; Launer LJ et al, 1999. Rates and riskfactors for dementia and Alzheimer’s disease: results from EURODEM pooled analyses.EURODEM Incidence Research Group and Work Groups. European Studies of Dementia.Neurology, 52, 78–84.

Prenatal stress

adverse events during fetal development (hypoxia, ischemic insults, or trauma) reduced length and weight of newborn

Low birth weight: frequent development of the metabolic syndrome (MetSyn)lower insulin sensitivity increased prevalence of T2DM, obesity, and hypertension

in adulthoodincreased risk for CVD in later years

Pruesner JC, 2011. Preventing Alzheimer Disease – An Attainable Goal? Alzheimer Rounds, 1(4),retrieved online on 16.03.2013 at http://www.alzheimerrounds.ca/crus/148-004%20English.pdf;Reynolds RM, 2010. Corticosteroid-mediated programming and the pathogenesis of obesity anddiabetes. J Steroid Biochem Mol Biol. 122(1-3):3-9; Barker DJ, 1995. Fetal origins of coronary heartdisease. BMJ. 311(6998):171-174

Epidemiological studies have linked low birth weight withcentral adiposity in adulthood

A study on 300 000 Netherlands men exposed in utero to a severe famine at the end of WW2:

• a significantly lower birth weight • significantly higher rates of obesity at the age of 19 years.

the effects were also detected in the offspring of these men (epigenetic effects)

Pruesner JC, 2011. Preventing Alzheimer Disease – An Attainable Goal? Alzheimer Rounds, 1(4), retrieved online on 16.03.2013 at http://www.alzheimerrounds.ca/crus/148-004%20English.pdf; Hales CN, Barker DJ, Clark PM, et al 1991. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ. 1991;303(6809):1019; Ravelli GP, Stein ZA, Susser MW 1976. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 295(7):349-353; Simmons R, 2008. Perinatal programming of obesity. Semin Perinatol. 32(5):371-374

Postnatal adversity

The 35-year follow-up of the Harvard Mastery of Stress Study:

low parental care or overprotection:in 95% of subjects who reported a low parental care there were detected:CVD, hypertension, and ulcers. high rate of alcohol and drug abuse

Pruesner JC, 2011. Preventing Alzheimer Disease – An Attainable Goal? Alzheimer Rounds, 1(4),retrieved online on 16.03.2013 at http://www.alzheimerrounds.ca/crus/148-004%20English.pdf;Russek LG, Schwartz GE, 1997. Perceptions of parental caring predict health status in midlife: a35 year follow up of the Harvard Mastery of Stress Study. Psychosom Med. 59:144-149

Johansson L et al study, 2010.

A 35-year longitudinal population study

Aim: To investigate the relationship between psychological stress in midlife and the development of dementia in late-life, on 1462 females aged 38–60 years

Results: an association between psychological stress in middle-aged women and

development of dementia (especially AD) was found 161 females developed dementia: 105 Alzheimer’s disease, 40 vascular dementia 16 - other dementias.

the risk was higher in females reporting frequent/constant stress

Johansson L et al., 2010. Midlife psychological stress and risk of dementia: a 35-year longitudinal population study. Brain, 133 (8): 2217-2224

Potential neurobiological mechanisms

Stressful events can trigger a cascade of reactions involving the stress hormones (glucocorticoids).

Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis (increased cortisol levels) occurs early in AD,

eventually leading to atrophy in the brain’s hippocampus.

Disturbances of the HPA axis have been associated with memory impairments.

Green KN et al 2006. Glucocorticoids Increase Amyloid-β and Tau Pathology in a Mouse Model of Alzheimer’s Disease. The Journal of Neuroscience, 30, 26(35): 9047-9056

Stress and MCI conversion to dementia

A number of illnesses are known to develop earlier or are made worse by chronic stress: heart disease, diabetes, cancer and multiple sclerosis.

Little research has been done on the experience of stress in people with MCI or AD

About 60% of people with mild cognitive impairment are known to go on to develop AD

Rissman RA et al, 2012. Corticotropin-releasing factor receptor-dependent effects of repeated stress on tau phosphorylation, solubility, and aggregation. PNAS Early Edition, retrieved online on 07.03.2012 at http://www.pnas.org/content/early/2012/03/22/1203140109.full.pdf+html |

The study at the University of Gothenburg, Sweden (published 2010) :

Aim:to analyse the relationship between psychological stress in midlife and the

development of dementia in late-life

1462 females aged 38–60 years examined in 1968, 1974, 1980, 1992 and 2000–2003: Psychological stress rating (according to a standardized question) Dementia diagnosis ( Diagnostic and Statistical Manual of Mental

Disorders criteria, neuropsychiatric examinations, informant interviews, hospital records and registry data).

Johansson L et al, 2010. Midlife psychological stress and risk of dementia: a 35-year longitudinal population study. Brain, 133 (8): 2217-2224

Results: 161 females developed dementia:

AD - 105 participants VaD - 40 Other dementias – 16

the risk of dementia was increased in females reporting frequent/constant stress

Reporting stress at one, two or three examinations was related to a sequentially higher dementia risk.

Conclusion:

It was detected an association between psychological stress in middle-aged women and development of dementia, especially AD.

Johansson L et al, 2010. Midlife psychological stress and risk of dementia: a 35-year longitudinal population study. Brain, 133 (8): 2217-2224

Psychosocial stress at work and the increased dementia risk in late life – a 6 years follow-up study on a dementia-free cohort of 913 community dwellers, aged 75+ years from the Kungsholmen Project, Sweden

Methods: A dementia-free cohort of 913 community dwellers, aged 75+ years from the Kungsholmen Project, a population-based follow-up study carried out in Stockholm, Sweden, was followed up for an average of 6 years to detect incident dementia and AD (third revised DSM).

Information on the lifespan work activities was collected. Psychological stress at work was estimated for the longest period of occupation as

well as for all occupations by using a validated psychosocial job exposure matrix on two dimensions: job control and job demands.

Cox proportional hazards model were used to estimate the Hazard ratios (HRs) and 95% confidence intervals (CIs) of dementia and AD in relation to different levels of job stress.

Hui-Xin Wang, Maria Wahlberg, Anita Karp, Bengt Winblad, Laura FratiglioniAgeing Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm UniversityAlzheimer’s & Dementia 8 (2012), 114-120

Psychosocial stress at work and the increased dementia risk in late life – a 6 years follow-up study on a dementia-free cohort of 913 community dwellers, aged 75+ years from the Kungsholmen Project, Sweden

Results: Low level of job control was associated with higher multivariate adjusted risk of dementia (HR=1.9. 95%CI: 1.2-3.0) and AD (HR=2.2, 95% CI: 1.2-3.9).

Low level of job demands alone was not significantly associated with increased dementia risk. When the two dimensions were combined into a four-category job-strain model, both high job strain (low control/high demand) and passive strain (both low control and demands) were related to higher risk of dementia and AD as compared with active job strain (both high). Vascular disorders did not mediate the observed associations.

Conclusions: Lifelong work-related psychosocial stress, characterized by low job control and high job strain, was associated with increased risk of dementia and AD in late life, independent of other known risk factors.

Hui-Xin Wang, Maria Wahlberg, Anita Karp, Bengt Winblad, Laura FratiglioniAgeing Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm UniversityAlzheimer’s & Dementia 8 (2012), 114-120

Acute psychological stress may change gene expression

DNA methylation an epigenetic mechanism related to mental and physical health and disease.

Provides a biological basis for gene–environment interactions relevant to mental health

Aberrant DNA methylation detected in various mental disorders: depression, psychotic disorders, post-traumatic stress disorder, autism, eating disorders, cancer etc.

early as well as later in life experiences can alter DNA methylation and affect gene expression and behavior.

Unternaehrer E et al, 2012. Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stressTranslPsychiatry , 2, e150. Retrieved online on 18.03.2013 at http://www.nature.com/tp/journal/v2/n8/pdf/tp201277a.pdf

Unternaehrer E et al, 2012. (University of Trier, Germany)

Investigations on 83 participants aged 61–67 years, before and after an acutepsychosocial stressor :

Quantitative DNA methylation in OXTR (oxytocin receptor) and BDNFR (brain-derived neurotrophic factor) genes,

blood samplings (pre-stress, as well as 10 and 90 min post-stress) the Trier social stress test.

Results: The stressful situation induces changes in the OXTR gene methylation (

expression) : increased within the first 10 min (the cells formed less oxytocin receptors) dropped below the original level (before the test) after 90 min (overstimulation of

receptor production).

Fuchikami M et al, 2010. DNA methylation profiles of the BDNF gene in patients with major depression. Int JNeuropsychopharmacol, 13: 147; Unternaehrer E et al, 2012. Dynamic after the ges in DNA methylation ofstress-associated genes (OXTR, BDNF) after acute psychosocial stressTransl Psychiatry , 2, e150. Retrievedonline on 18.03.2013 at http://www.nature.com/tp/journal/v2/n8/pdf/tp201277a.pdf

There are a lot of scientific works that report the beneficial effects ofphysical and mental exercise (mild stress and challenges)

Clinical applications of exercise-mediated hormesis are evolving

• for slowing down aging processes • for preventing the aging-related neurodegenerative pathology

are targets for investigation.

Several authors are talking about “the hormesis revolution”, including in the MCI and AD approach.

Hormesis: A Revolution in Biology, Toxicology and Medicine. Mattson MP, Calabrese EJ Eds., Springer Science+Business Media LLC, 2010;

As synthesized by Rothman MS, Mattson MP (2010):

Mild, intermittent, beneficial stressors (exercise, dietary energy restriction and cognitive challenges) are valuable tools in aging and neurodegenerative diseases management

Other valuable interventional tools:

Minimization of adverse chronic stressors (psychosocial stress, sleep deprivation etc.), are the other face of the matterImprovement of (brain) cell energy metabolism through an adequately managed nutrition Management of glucocorticoid cascade, depending on stress type: acute or chronic Upregulation of the expression of neurotrophic factors ( drugs that address serotonergic and/or noradrenergic signaling pathways) – to counteract the maladaptive responses to stress of the neural circuits involved in learning and memory

Rothman MS, Mattson MP, 2010. Adverse Stress, Hippocampal Networks, and Alzheimer's Disease. Neuromolecular Med. 12(1): 56–70

Conclusions

Exposure to various kinds of stress is a normal coordinate ofhuman life

Is stress involved in neurodegenerative diseases like MCI andAD?

The answer is YES !

Conclusions

Growing evidence documents that various types of “bad stress” are involved in MCI onset and its conversion to AD

Like all the other inner and outer determinants of our life, “bad stress” is deeply involved (even at molecular level) in the susceptibility to a disease and its onset

Conclusions

A large part of psychological, familial, occupational, social and economical stressors can not be eliminated

We have to learn how to cope with stress (education in the context of Participative Medicine)

Conclusions

We have to learn how to manage “bad” and “useful” stress in our benefit

The challenge of hormetic stressors is able to improve: our knowledge about neurodegeneratavie pathology, including the

cognitive one our arsenal of interventional means

Conclusions

The acquired research data on stress seem able to profile a better future in the area of multifactorial approach of dementia prevention, diagnosis, and development of medical and non-medical disease-modifying means.

Consecutively, these new findings may significantly result in improved public health strategies and management of dementia care costs.

Conclusions

Sustained further research (and financial support) is needed to deeply investigate the impact of environmental, modifiable! risk factors involved in the susceptibility to develop dementias

New, knowledge-based research and clinical paradigms on stress as risk factor for neurodegenerative diseases must be envisaged as innovative proposals in the framework of the European Initiative Programme on Active and Healthy Aging, launched by the EC in 2011

Chapter 3

Stress Evaluation and ManagementAn Innovative Practical Approach in Romania done by AAIF

Why stress management ?

Why stress management ?

Well, maybe not 80%, but still stress is a large part of our

lives…

From top managers to simple task executing employees –

everyone is going through difficult moments at work

Getting over these moments with a calm attitude and taking

the correct decisions under stress makes the

difference between success and failure in most of the cases

Acute and Chronic Stress

Is stress good ….?

Short time exposure to stress factors (or acute stress) – the

releasing of stress hormones have a positive, activating effect

on the adaptive mechanisms

This is preparing the organism for an adequate answer to the

more severe forms of stress and is promoting long term

survival

Furthermore it stimulates the development of new brain cells

responsible for memory

…or is stress bad?

On the other hand, the chronic exposure to stress factors leads to an overcoming of the adaptive mechanisms with a large, extended impact on all organs and systems from the human body

At CNS (Central Nervous System) level, the chronic stress is impairing the development of the neurons within hippocampus, prefrontal cortex and amygdala (areas responsible for the superior cognitive functions and emotions control) thus leading to troubles in attention, concentration, memory and to anxiety and depression

Recent studies have proven that stress at work is a significant risk factor for AD (Alzheimer’s Dementia) – see next couple of slides

Recent scientific data proving that stress at work is a risk factor for AD

The Realities of Alzheimer’s earlier debut

“My name is Michael Ellenbogen, and I am living with Alzheimer’s and trying to make a difference.

I was previously a high-level manager in the telecommunication industry.

In 2008, I was diagnosed with younger-onset Alzheimer’s disease (YOAD) after struggling to get a diagnosis since my first symptoms at age 39.

Losing my job and not being able to work had a huge impact on my life as I was a workaholic. I am now an Alzheimer’s advocate and a spokesperson for the Alzheimer’s Association (US) as a member of its national 2012 Early-Stage Advisory Group.”

“Cognitive Decline Can Start at Age 45”Emma Hitt, PhD – BMJ. 2011;343. Published online January 5, 2012

January 6, 2012 — Cognitive decline is detectable in persons aged 45 to 49 years and may not uniformly start later, in persons aged approximately 60 years, as previously thought, new research suggests.The study, using data from the longitudinal Whitehall II cohort study, followed participants aged 45 to 70 years at baseline using 3 cognitive assessments over a period of 10 years.The investigators report that average performance in all cognitive domains except vocabulary, which is known not to be affected by age, declined over the follow-up period in all age groups, including persons aged 45 to 49 years.

“The Realities of Alzheimer’s and Overcoming Stigma”Michael Ellenbogen – Alzheimer’s Association blog, Posted online September 21, 2012

OK, so this looks bad!Are there any good news?

Yes!

The good news is that early identification & quantification of individual stress factors,

combined with personalized & participative interventions can prevent or reduce these risks

And just what do these sentences mean?

“Early identification & quantification”

“Personalized & participative interventions” :

The diagnosing process developed by our medical research

team leads to the best solutions adequate for each person;

Nevertheless, no initiative (nor therapy) can be successful

without the active participation of the person involved!!!

Each individual has his/her own personal life history, genetic and epigenetic

profile;

These have to be assessed appropriately in order to understand the

particular reactivity under stress

The impact is at two levels:

o Improvement of life quality and personal and professional performance of the primary end-user (the employee aged 35-60 years working in stressful conditions)

o Reduction of absenteeism and staff fluctuation, in the benefit of the secondary end-user (employing company)

What solution?The Lifestyle & Stress Evaluation and Management

Competitive edge from healthy employees

Occupational and organizational well-being starts from the well-being of individuals.

•Thus, the starting point of our well-being services is the individual and the importance

of individual motivation in making lifestyle changes.

•Without internal motivation even the most effective measures are powerless.

•The Lifestyle Assessment shows the areas of one’s lifestyle that need the most

attention. After this, it’s possible to set goals and specify action points for each

employee and the organization as a whole.

•Investment in the health and well-being of your employees is an investment in the

success of your company!

Competitive edge from healthy employees

Key benefits:

•New and inspiring way to promote health and well-being

• Complete method motivates employees with different lifestyles

• Round-the-clock measurement combines work, leisure time and sleep

• Guidance for coping and recovery management, based on individual

measurement data

•Promotion of the work and functional capacity of your employees

•Improved coping at work

•Increased staff motivation

•Development of healthy working habits and practices

•Reduction of sick leave related costs

•Reduction in early retirement

PERSONALREPORT

FEEDBACK FROM OUR SPECIALIST

INITIAL DATA COLLECTION & MEASUREMENTS

FOLLOW-UP

LIFESTYLE ASSESSMENT STEPS

At 6 months and 1 year - to assess how the users

managed to improve stress management, exercise and/or quality of sleep.

1. Structured interview2. Standardized tests3. HRV measurements – 3

days during work, sleep and leisure time

4. Collection of stress markers: Cortisol from Saliva & Neurotransmitters from Urine

Personal advise and Action Plan - for improving

well-being and performance

1 2 3 4

COMMON WAYS OF IMPROVING ONE’S WELL-BEING

• Recognize causes of stress and improve stress management

• Increase moments of recovery

• Find the right type of exercise

• Increase amount of sleep (34%)

• Reduce smoking / use of alcohol

Data on Well-Being and Performance

A new, exciting method to boost employee wellbeing

and performance

Overview of the well-being of your organization(anonymous group report provided)

Reduced sick leave expenses and risk of

early retirement

Healthy employees that perform better, closer to theiroptimal level

Advice for developing personal well-being and performance (personal report for each employee)

See how to direct employee wellness investments

Ensure the well-being of possible risk groups

Control health care costs

WHAT DOES THE STRESS MANAGEMENT AND LIFESTYLE ASSESSMENT OFFER TO YOUR BUSINESS?

GROUP REPORT – A REAL EXAMPLE (24 BANKING MANAGERS)

Physical activity index Share of recovery during sleep (%)

Quality of recovery (RMSSD)

Recommendation Good Moderate Poor

Assessments

Measurements

Average age

Average Body Mass Index

24

97

41

23.1

18.06.2014Reporting date

Average share of stress per day

Overall Stress and Recovery

54%

19%Average share of recovery per day

Average values of stress and recovery in Firstbeat databaseStress: 47%Recovery: 25% (Firstbeat recommends at least 30%)(Source: Firstbeat user database 2013)

49min

Recovery During Daytime

Good60 min or more

Moderate15 - 59 min

Poor0 - 14 min

Average recovery during leisure time 12min

Good30 min or more

Moderate10 - 29 min

Poor0 - 9 min

Average recovery during work time

Physiological Reactions During Sleep Periods

Average share of recovery during sleep 50%

31Average quality of recovery (RMSSD)

7h 44minAverage time used for sleeping

Percentage of recovery during the sleep periods. Measurement breaks are excluded from analysis.

Quality of recovery is determined from a heart rate variability based index (RMSSD). RMSSD is a measure of heart rate variability indicating the quality of recovery. Low values of RMSSD during sleep indicate poor recovery. Higher values indicate enchanced recovery.

The need for sleep can vary significantly between individuals. The time used for sleeping has been derived from the people's journals.

Good PoorModerate

Good Moderate75 – 100% 50 - 74%

Poor0 - 49%

Goodmore than 7 h

Poorless than 5,5 h

Moderate5,5 - 7 h

Personal well-being means making choices in daily life

1) Stress management

•Do you recover enough?

•Do your work days include any breaks?

•Prolonged stress without regular and sufficient recovery

weakens your body’s defenses and increases the risk of

cardiovascular and lifestyle diseases.

•First beat Assessments will demonstrate the sufficiency of your

recovery and highlight especially stressful periods during work

and leisure time.

•Even small changes can significantly improve your well-being!


2) Good night and good morning!

• Brain capacity drops by 40% already after five poorly slept

nights.

• The consequences of sleep deprivation can be seen in many

areas: at work, during leisure time and physiologically in your

body.

• Long-term sleeplessness puts you at risk of many diseases

and is also an occupational safety risk.

• With Lifestyle Assessments we help to evaluate the quality

and sufficiency of your sleep and look for solutions to get

better recovery.


3) Are you active enough?

•Every fitness-enhancing physical activity session is an

investment in your future – good fitness can increase the

functional quality of your life by as many as 20 years!

•Our Lifestyle Assessments will show if you are physically active

enough and if your physical activity is intensive enough to

provide positive health effects and to improve your fitness level.

•In addition to physical activity recommendations you have the

option to start using an individual web-based training program.

How it works? Protocol description:1) Data/info collection

1.1. First visit: 1.5 – 2.0 hrso Structured interview regarding the personal natural life history

o Battery of standardized tests for the: • cognitive performance assessment,

• psychometric evaluation,

• emotional intelligence evaluation

Data/info collection – cont.

1.2. Life Style Assessment & Stress level measurement: 3-4 dayso Continuous monitoring of HRV (Heart rate variability) with the

advanced technology from Firstbeat (a detailed presentation within few slides)

Stress reactions

Recovery...

Oxygen consumption

Firstbeat measures heart rate variability to analyze these

functions

Heart rate variability (HRV) contains information about

key physiological functions

Relaxation

Firstbeat produces a comprehensive report about personal well-being

Data/info collection – cont.

1.3. Personalized set of specific (non-invasive) stress biomarkers:

o Neurotransmitter diagnosis (in 2nd morning urine)

• Norepinephrine

• Epinephrine

• Dopamine

• Serotonin

o Cortisol day-profile (saliva) at 8, 14, 20 h

Protocol description:2) Personalized Assessment & Intervention Plan

A personalized report is generated, which:

o Contains all the relevant outcomes gathered from

previous phase and

o Offers the individualized integrated solutions for

each participant, including:

• Lifestyle & nutrition management and professional advices

• Personal counselling on emotional and work-related stress management

• Innovative medical recommendations (if applicable) - based on both

Conventional and Integrative Medicine drug and non-drug therapies,

remedies and practices ;

Protocol description:3) Regular Follow-up – optional (but highly recommended)

All participants should be called upon for follow-up visits at 6 months and 1 year, in order to assess their evolution and to take all the adequate additional measures that might be required

NB: Regardless if this follow-up is implemented or not, all participants will have permanent access at our medical & professional team for continuous feedback & counseling

Measured information helps recognize what your well-being is made of

Manage stressRecognize activities that cause stress

Enhance recovery

See how you recover during sleep

Exercise rightSee the effect of your exercise

FIRSTBEAT lifestyle assessment – brief description

Well-being is created during work, leisure and sleep

LIFESTYLE ASSESSMENT BACKGROUND

Stress reactions

Recovery

... Oxygen consumption

Firstbeat measures heart rate variability to analyze these functions

Heart rate variability (HRV) contains

information aboutkey physiological

functions

Relaxation

Firstbeat produces a comprehensive report

about personal well-being

SEE WHAT YOUR WELL-BEING CONSISTS OF

BUSY DAY WITH NO MOMENTS OF RECOVERY

DAY WITH GOOD RECOVERY

Work

Lunch break Nap Reading

Customer meeting

Breakfast

STRESS RECOVERY

PHYSICAL ACTIVITY


NIGHT WITH POOR RECOVERY

NIGHT WITH GOOD RECOVERY

Reading

Overtime work

Dinner

STRESS RECOVERY

PHYSICAL ACTIVITY


DAY WITH NO EXERCISE

DAY WITH EXERCISE

Riding bike to work. 36min, 155 kcalThis type of exercise improves your aerobic fitness

Gym. 30min, 152 kcal

STRESS RECOVERY

PHYSICAL ACTIVITY

Instead of Conclusion:

Thank you for attention

and your feedback!

HealthyBrain Aging

Healthy Aging

Luiza Spiru, MD, PhD

[email protected]

Documents

Next Step in Anti-aging Innovation - Naresuan University