Alzheimer’s diseaseAlzheimer’s disease

Vasileios Papaliagkas MD/PhD, Georgios Vasileios Papaliagkas MD/PhD, Georgios Anogianakis MD/PhDAnogianakis MD/PhD

Department of Experimental Physiology, Medical School Aristotle University of Department of Experimental Physiology, Medical School Aristotle University of ThessalonikiThessaloniki

DirectorDirector : Professor Georgios Anogianakis: Professor Georgios Anogianakis

1. 1. INTRODUCTIONINTRODUCTION

Memory in ancientryMemory in ancientry

Dementia is Dementia is mentionedmentioned

In Roman medical In Roman medical textstexts

In CiceroIn Cicero

«there is no crime when the person who performs it, is in a dementia state,

at the moment of performance»

Napoleo code, article 10 (1808)

Law and dementia

In In 1910 1910 German German doctor Emil Kraepelindoctor Emil Kraepelin first used first used ««Alzheimer’s diseaseAlzheimer’s disease” ” in his 8in his 8thth edition of edition of his his Textbook of PsychiatryTextbook of Psychiatry

He observed the same He observed the same neuropathological neuropathological changeschanges

Kraepelin, E. Compendium der psychiatrie, 8th edition. Leipzig, DE, 1910

2020thth Century Century

World opinion about World opinion about dementiadementia Russia:Russia: Hakkeboutsch and Geier Hakkeboutsch and Geier

Alzheimer's disease a variety of the Alzheimer's disease a variety of the involution psychosis and involution psychosis and

Simchowicz : a severe form of senile Simchowicz : a severe form of senile dementia. dementia.

Ziehen does not mention Alzheimer's Ziehen does not mention Alzheimer's disease in his major review of the senile disease in his major review of the senile dementias. dementias.

World opinion about World opinion about dementiadementia-2-2 Lugaro wrote: "For a while it was believed Lugaro wrote: "For a while it was believed

that a certain agglutinative disorder of that a certain agglutinative disorder of the neurofibril was considered as the the neurofibril was considered as the main marker of the pre-senile form [of main marker of the pre-senile form [of senile dementia], and that this was senile dementia], and that this was hurriedly baptised as Alzheimer's hurriedly baptised as Alzheimer's disease." disease."

He went on to state that he believed that He went on to state that he believed that the latter was only a variety of senile the latter was only a variety of senile dementiadementia

USA opinionUSA opinion

USA:USA: Fuller asked: "Why a special clinical Fuller asked: "Why a special clinical designation – Alzheimer's disease – since, after designation – Alzheimer's disease – since, after all, they are but part of a general disorder?" all, they are but part of a general disorder?"

New York Neurological Society, Ramsay Hunt New York Neurological Society, Ramsay Hunt asked Lambert, the presenter of a case of asked Lambert, the presenter of a case of 'Alzheimer's disease' that "he would like to 'Alzheimer's disease' that "he would like to understand clearly whether he made any understand clearly whether he made any distinction between the so-called Alzheimer's distinction between the so-called Alzheimer's disease and senile dementia, other than...in disease and senile dementia, other than...in degree and point of age". degree and point of age".

Lambert : the underlying pathological Lambert : the underlying pathological mechanisms were the samemechanisms were the same

Extract from: Extract from: Alzheimer A. Über eine Alzheimer A. Über eine eigenartige Erkrankung der Hirnrinde eigenartige Erkrankung der Hirnrinde Allgemeine Allgemeine Zeitschrift fur Psychiatrie und Psychisch-Zeitschrift fur Psychiatrie und Psychisch-gerichtliche Medizingerichtliche Medizin. 1907. 1907

““One of the first disease One of the first disease symptoms of a 51-year-old symptoms of a 51-year-old woman was a strong feeling of woman was a strong feeling of jealousy towards her husband. jealousy towards her husband. Very soon she showed rapidly Very soon she showed rapidly increasing memory increasing memory impairments; she could not impairments; she could not find her way about her home, find her way about her home, she dragged objects to and she dragged objects to and fro, hid herself, or sometimes fro, hid herself, or sometimes thought that people were out thought that people were out to kill her, then she would to kill her, then she would start to scream loudly.start to scream loudly.””

““From time to time she From time to time she was completely delirious, was completely delirious, dragging her blankets dragging her blankets and sheets to and fro, and sheets to and fro, calling for her husband calling for her husband and daughter, and and daughter, and seeming to have auditory seeming to have auditory hallucinations. Often she hallucinations. Often she would scream for hours would scream for hours and hours in a horrible and hours in a horrible voice.” voice.”

Although the risk of developing AD increases with age – in most people with AD, symptoms first appear after age 60 – AD is not a part of normal aging. It is caused by a fatal disease that affects the brain.

Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills.

What is AD?

Slide 4

AD Statistics….

• AD is the most common cause of dementia among people age 65 and older.

• Scientists estimate that around 26 million people now have AD.

• For every 5-year age group beyond 65, the percentage of people with AD doubles.

What is AD?

• By 2050, 13.2 million older Americans are expected to have AD if the current numbers hold and no preventive treatments become available.

Slide 5

Cognitive ability

Daily

activitie

s Behaviour

Symptom types in ADSymptom types in AD

Alzheimer’s Disease and DementiaAlzheimer’s Disease and Dementia

DementiaDementia: : a clinical syndrome of decline in a clinical syndrome of decline in memory and other cognitive abilities severe memory and other cognitive abilities severe enough to interfere with a person’s daily enough to interfere with a person’s daily activitiesactivities

Alzheimer’s diseaseAlzheimer’s disease: a progressive neurological : a progressive neurological disease; most common cause of dementia, disease; most common cause of dementia, accounting for 60-80% of all dementiaaccounting for 60-80% of all dementia

Other causes/types of dementiaOther causes/types of dementia: vascular : vascular dementia; frontotemporal dementia (FTD); dementia; frontotemporal dementia (FTD); Lewy body dementia, mixed dementiaLewy body dementia, mixed dementia

Normal,

Alzheimer’s disease, 75 years old

Volume of Hippocampus and Rate of Shrinkage Predicts Crossover from MCI to AD

Percent Annual Decline in Hippocampal Volume

00.5

11.5

22.5

33.5

4

Control MCI AD

StableDecliner

Jack CR, et al, Neurology 55: 484-489, 2000De Leon MJ, 1999

Figure 1. Scans of Patients with Probable Alzheimer's Disease. In Panel A, a magnetic resonance image shows cortical atrophy and ventricular enlargement. In Panel B, a positron-emission tomographic scan shows reduced glucose metabolism in the parietal lobes bilaterally (blue-green) as compared with more normal metabolism in other cortical areas (yellow).

NEJM.Volume 351:56-67 July1,2004. Number 1

Normal aginghttp://www.med.harvard.edu/AANLIB/cases/caseNA/pb9.htm

The diseaseThe disease…..…..

The causes are not yet completely known. It is irreversible It worsens continuously and processes

slowly. 160 thousand in Greece, 6 million people in

Europe and 26 million people worldwide suffer from Alzheimer’s disease

There is a need for early diagnosis and finding of appropriate treatment

I thought that elephants never forgot. According to the results you suffer from Alzheimer’s disease…

Η Νόσος Alzheimer δεν κάνει διακρίσεις!AD does not make distinctions….AD does not make distinctions….

Alzheimers versus normal brainAlzheimers versus normal brain

Normal versus degenerating Normal versus degenerating neuronneuron

Rita Hayworth

AD does not discriminate…AD does not discriminate…

AD does not discriminate…….AD does not discriminate…….

Margaret Thatcher one of the most commanding figures of the 20th Century, struggles to finish sentences, does not know where she lives and even forgets that her husband Denis is dead.

AD does not discriminate…AD does not discriminate…

Joe Adcock, baseball playerMabel Albertson, actorDana Andrews, actorRudolph Bing, opera impresarioJames Brooks, artistCharles Bronson actor, film directorAbe Burrows,authorCarroll Campbell, Former Rebublican SenatorJoyce Chen, chefPerry Como, Singer entertainerAaron Copland, composerWillem DeKooning, artistJames Doohan, actorThomas Dorsey, singerTom Fears, professional football player and coachLouis Feraud, fashion designerArlene Francis, actor Mike Frankovich, film producerJohn Douglas French, physicianBarry Goldwater, Senator of ArizonaRita Hayworth, actressRaul Silva Henriquez, Roman Catholic cardinal, human rights advocate

Charlton Heston actor and political activistMervyn Leroy, directorJack Lord, actorRoss MacDonald, authorBurgess Meredith, actorIris Murdoch, authorEdmond O’Brien, actorArthur O’Connell, actorMarv Owen, baseball playerMolly Picon, actorOtto Preminger, directorBill Quackenbush, professional hockey playerRonald Reagan, 40th President of USAHarry Ritz, performerSugar Ray Robinson, boxerNorman Rockwell, artistSimon Scott, actorIrving Shulman, screenwriterBetty Schwartz, Olympic gold medal winner in track eventsKay Swift,composerAlfred Van Vogt, science fiction writer

2. 2. EPIDEMIOLOGYEPIDEMIOLOGY

25/06/0925/06/09

EPIDEMIOLOGYEPIDEMIOLOGY

PrevalencePrevalence, , 1010% % over 70 in Europeover 70 in EuropeIn GreeceIn Greece 6% 6% over over 70 70 years ikdyears ikd

Tsolaki M. et al, AJAD, 1999Tsolaki M. et al, AJAD, 1999

160 160 thousand patients in Greece thousand patients in Greece Ελλάδα, 26 Ελλάδα, 26 million worldwidemillion worldwide

Percentage of People Age 71+ with Dementia byPercentage of People Age 71+ with Dementia byGender, ADAMS, 2002.Gender, ADAMS, 2002.

Source: Plassman, BL; Langa, KM; Fisher, GG; et al. “Prevalence of Dementia in the United States: The Aging, Demographics, and Memory Study.” Neuroepidemiology 2007;29:125-132.

Women are more likely than mento have Alzheimer’s and otherdementias, primarily because women ive longer, on average, and their longer life expectancy increases the time during which they could developthese diseases.

Projected Prevalence of Alzheimer’s Projected Prevalence of Alzheimer’s Disease 2000-2047Disease 2000-2047

012345678

2000 2010 2020 2030 2040

Prevalence in millions

Percentage of women and men that will develop Percentage of women and men that will develop DementiaDementia (1) (1) or Alzheimer’s Disease (or Alzheimer’s Disease (22) in the rest of ) in the rest of their lives if they are 55their lives if they are 55 years old today, Framingham years old today, Framingham

Heart StudyHeart Study

Source: Beiser, A; Seshadri, S; Au, R; and Wolf, PA. Departments of Neurology and Biostatistics, Boston University Schools of Medicine and Public Health, Unpublished Data from the Framingham

Heart Study, 2008.

(1) (2)

1/6 of women and 1/10 of men will develop AD

Prevalence of AD by ethnic group and Prevalence of AD by ethnic group and years of schoolyears of school

05

101520253035

AfricanAmerican

CaribbeanHispanic

non-HispanicWhite

13+12

7 - 110 - 6

Years

of sc

hool

% w

ith A

D w

ithin

eth

nici

ty

Percentage of dementias in people agedPercentage of dementias in people aged 71+71+

Source: Plassman, BL; Langa, KM; Fisher, GG; Heeringa, SG; Weir, DR; Ofstedal, MB; et al. “Prevalence of Dementia in the United States: The Aging, Demographics, and Memory Study.” Neuroepidemiology 2007;29:125-132.

COST OF ALZHEIMER’S COST OF ALZHEIMER’S DISEASEDISEASE

ECONOMIC IMPACT OF ADECONOMIC IMPACT OF AD 2 million AD patients in nursing homes2 million AD patients in nursing homes

– Projection to California – 240,000Projection to California – 240,000 Nursing homes cost - $120 to $160 per dayNursing homes cost - $120 to $160 per day Annualized cost of nursing homes rangesAnnualized cost of nursing homes ranges

– from $40,000 to $70,000 per yearfrom $40,000 to $70,000 per year Nursing Home Care of AD patients costs $80 billion Nursing Home Care of AD patients costs $80 billion

per yearper year– for life-time cost – about $175,000 per patientfor life-time cost – about $175,000 per patient

The majority of patients live at home and The majority of patients live at home and are cared for by family and friendsare cared for by family and friends

With lost wages of patients and families plus costs With lost wages of patients and families plus costs for non-nursing home patients:for non-nursing home patients:– Total costs: $Total costs: $120 billion annually120 billion annually ( (Am J Publ HlthAm J Publ Hlth))– Projection to California – $14.5 billion annually!Projection to California – $14.5 billion annually!

Cost of AD in the USACost of AD in the USA

Family and Other Unpaid CaregiversFamily and Other Unpaid Caregivers In 2007, 9.8 million Americans age 18+ provided In 2007, 9.8 million Americans age 18+ provided

unpaid care for a person with Alzheimer’s disease unpaid care for a person with Alzheimer’s disease or another dementia. or another dementia.

About 250,000 children age 8 to 18 provided About 250,000 children age 8 to 18 provided

unpaid care for a person with Alzheimer disease unpaid care for a person with Alzheimer disease or another dementia.or another dementia.

Family and other unpaid caregivers provided Family and other unpaid caregivers provided 8.4 billion hours 8.4 billion hours of care valued at of care valued at $89 billion$89 billion

Prevalence of Alzheimer’s Disease in USPrevalence of Alzheimer’s Disease in US

In 2008, an estimated 5.2 million Americans In 2008, an estimated 5.2 million Americans had Alzheimer’s disease, includinghad Alzheimer’s disease, including::

~ about 5 million Americans age 65 and older about 5 million Americans age 65 and older State State DataData

~ about 200,000 Americans under age 65 about 200,000 Americans under age 65

More women than men have Alzheimer’s More women than men have Alzheimer’s disease because women live longer, on disease because women live longer, on average, than menaverage, than men

New Cases of Alzheimer’s DiseaseNew Cases of Alzheimer’s Disease In 2008, about 445,000 Americans age 65+ will In 2008, about 445,000 Americans age 65+ will

develop Alzheimer’s disease – develop Alzheimer’s disease – 1 new case every 71 seconds1 new case every 71 seconds

Without a way to prevent or cure Alzheimer’s or a Without a way to prevent or cure Alzheimer’s or a treatment that can delay onset or progression:treatment that can delay onset or progression:In 2050, almost 1 million Americans age 65+ will In 2050, almost 1 million Americans age 65+ will develop Alzheimer’s disease – develop Alzheimer’s disease –

1 new case every 33 seconds1 new case every 33 seconds In 2050, about 13 million Americans will have In 2050, about 13 million Americans will have

Alzheimer’s diseaseAlzheimer’s disease

Epidemiology of AD – Time for Epidemiology of AD – Time for ChangeChange

Behavior and Life StyleFactors

Cardio/CerebrovascularFactors

Genetics and Primary Biomarkers

COST OF AD IN GREECECOST OF AD IN GREECE

21 21 thousand Euros/year thousand Euros/year ((OrologasOrologas et et alal 2005) 2005)

231 231 euros/montheuros/month in initial stagesin initial stages

1267 1267 euros/month in final stageeuros/month in final stage ((Kyriopoulos et al, Kyriopoulos et al, 2005)2005)

EPIDEMIOLOGYEPIDEMIOLOGY-21-21stst century century

Developing countriesDeveloped countries

Num

ber of patients with dem

entia (in m

illions)

Number of patients with dementia in developed and developing countries

Χρόνος

Prevalence of ADPrevalence of AD

Kurz A. Eur J Neurol 1998; 5(Suppl 4): S1-8Wimo A et al. Int J Geriatr Psychiatry 1997; 12: 841-56

0

10

20

30

40

50

60

60-64 65-69 70-74 75-79 80-84 85+ 95+Age (years)

Pre

vale

nce

(%)

1% 2% 4%8%

16%

30%

50%

Prevalence of AD-2Prevalence of AD-2

4949

Alzheimer’s disease, a serious health Alzheimer’s disease, a serious health problemproblem

Source: Alzheimer’s Association calculations using data from Evans, D. et al (1990) and US Census Bureau1 “Deaths: Preliminary Data for 2004,” National Vital Statistics Report, Volume 54, Number 19, June 28th, 20062 2nd International Conference on Prevention of Dementia

AD prevalence is 5 million in the USA, and will increase in 14 in 2050

0

2

4

6

8

10

12

14

16

2000 2010 2020 2030 2040 2050

Year

Projected number of Americans with AD

27 million suffer from AD. In 2050, they will be over 100

AD is the 7th cause of death

Heart problemsCancerStrokeΧρόνια χαμηλάRespiratoryDiabetesAlzheimer’s disease Flu and pneumoniaKidney problems

2004 Deaths

654 k550 k150 k124 k109 k73 k66 k61 k43 k

% Change

-6.4-2.9-6.5-3.5-1.9-3.61.4

-7.3-0.7

MM

5050

Συχνότητα θανάτου/100χιλΣυχνότητα θανάτου/100χιλ

Ivan Casserly, Eric Topol. Lancet 2004

Number of patients that die from serious diseases Number of patients that die from serious diseases from years from years 22000 to 2005000 to 2005..

Sources: Centers for Disease Control and Prevention, National Vital Statistics Reports, and Reports of the American Cancer Society.A13

Progression of AD

Εισαγωγή σε ίδρυμα

Feldman et al. Clinical Diagnosis and Management of Alzheimer’s Disease. 1999:249-268.

MM

SE

Years

Loss of Functional independance

0

5

10

15

20

25

30

1 2 3 4 5 6 7 8 9

Mild-Moderate

Early stage

Severe

Behavioural problems

Cognitive symptoms

MCI

Deaths From Alzheimer’s DiseaseDeaths From Alzheimer’s Disease

In 2005In 2005: 71,696 Americans died from : 71,696 Americans died from Alzheimer’s disease (as shown on death Alzheimer’s disease (as shown on death certificate)certificate)

Alzheimer’s disease was the 7Alzheimer’s disease was the 7thth leading cause of leading cause of death for Americans of all ages and the 5death for Americans of all ages and the 5thth leading cause of death for Americans age 65+leading cause of death for Americans age 65+

The number of people who died from Alzheimer’s The number of people who died from Alzheimer’s disease increased by disease increased by 44.7% from 2000 to 200544.7% from 2000 to 2005

8 years average. Range – 2-20 years

Stages of ADStages of AD

MILD2-4 Years

MODERATE2-10 Years

SEVERE1-3 Years

AD p

reva

lenc

e (m

illions

)AD p

reva

lenc

e (m

illions

)

Delay Delay (years)(years)

00

.5.5

11

22

55

19971997 20072007 20172017 20272027 20372037 20472047

YearYear

88

66

44

22

00

Brookheimer et al. Am J Pub Health. 1998;88:1337-1342.Brookheimer et al. Am J Pub Health. 1998;88:1337-1342.

Effect of the delay in the initiation of AD in its’ prevalence (in the USA)

5 years of delay in the diagnosis of the disease is equivalent with 50% reduction in its 5 years of delay in the diagnosis of the disease is equivalent with 50% reduction in its prevalenceprevalence

Alzheimer’s Disease Prevention Initiative

No Disease,No Symptoms

Early BrainChanges,

No Symptoms

Mild MemoryLoss

Mild, Moderate and Severe Impairment

Disease ProgressionDisease Progression

Mild Cognitive

Impairment

Pre-symptomatic

ADNormal AD

PrimaryPrevention

SecondaryPrevention Treatment