Dementia Vs Delirium

Dr Yau Weng Keong Geriatric Unit, Department of Medicine Hospital Kuala Lumpur

Will Cover the followings

Introduction to dementia The spectrum of cognitive dysfunction Evaluation of memory problems Management Non-pharmacological management Pharmacological management Whats in the future for dementia What about Delirium Conclusion

Will Cover the followings

Introduction to dementia The spectrum of cognitive dysfunction Evaluation of memory problems Management Non-pharmacological management Pharmacological management Whats in the future for dementia What about Delirium Conclusion

World is Ageing!

DEMOGRAPHIC TIME BOMB

How common is dementia?

Prevalence rates (%) of dementia in people aged 60 years of age and older as assessed in four meta-analyses
Age group (years) 6064 6569 7074 7579 8084 8589 9094 9599 Meta-analyses
Jorm et al, 1987 Hofman et al, 1991 Ritchie et al, 1992 Ritchie & Kildea, 1995

0.7 1.4 2.8 5.6 10.5 20.8 38.6

1.0 1.4 4.1 5.7 13.0 21.6 32.2 34.7

0.9 1.6 2.8 4.9 8.7 15.5 24.5 36.7

1.5 3.5 6.8 13.6 22.3 31.5 44.5

Jorm et al 1987; Hofman et al 1991; Ritchie et al 1992; Ritchie & Kildea 1995

Prevalence of dementia and cognitive impairment in Malaysia

Community
Authors Krishnaswamy et al, 1997 Fadhilah et al, 1996 Sherina et al, 2004 Aizan et al, 2003 24% 14.4% 45% 36.5% Cognitive Impairment Dementia 6% 6%

Long Tern Care

Hasanah et al, 1996 Al-Jawad et al, 2008

There have been few prevalence studies of dementia in Malaysia.

National Health and Morbidity Survey (NMHS-III, 2006) - 19.5% (aged 70-74 years) mental health problems

Alzheimers disease Estimated impact on US businesses

Itemizing the Impact Caregivers
Caregiver absenteeism Productivity loss Replacement of caregivers who leave Continuing insurance for workers on leave, fees to temp agencies, and Employee Assistance Programs 7.89 13.22 3.59 1.33

In Billions (U.S.$)

Caregiving Total Medical Care and Medical Research

Business share of healthcare costs Business share of research on Alzheimers

26.03
7.09 0.05

Medical Total
Total

7.14
$33.17

Adapted from Koppel R, Dept. Sociology, Univ. Pennsylvania (1998)

Prevalence and Treatment Rates

Prevalence1 Diagnosed2 Treated with AChEI3

2000 1800 1600 1400 1200 1000 800 600 400 200 0 Mild Moderate

Number of Patients (thousands)

Severe

Sources: 1. Hebert LE, Scherr PA, Bienias J, et al. Arch Neurol. 2003;60:1119-1122. 2. Datamonitor AD Treatment Algorithms. 2002. 3. Market Measures. 2003.

AD is Under-diagnosed

Early Alzheimers disease is subtle, the diagnosis continues to be missed

it is easy for family members to avoid the problem and compensate for the patient physicians tend to miss the initial signs and symptoms

Less than half of AD patients are diagnosed

Estimates are that 25% to 50% of cases remain undiagnosed Diagnoses are missed at all levels of severity: mild, moderate, severe

Undiagnosed AD patients often face avoidable social, financial, and medical problems Early diagnosis and appropriate intervention may lessen disease burden No definitive laboratory test for diagnosing AD exist

Evans DA. Milbank Quarterly. 1990; 68:267-289

Will Cover the followings

Introduction to dementia The spectrum of cognitive dysfunction Evaluation of memory problems Management Non-pharmacological management Pharmacological management Whats in the future for dementia What about Delirium Conclusion

Prevention

Prevention

Treatment Treatment

No Disease, function)(failure to recognize or identify Early Brain Mild Memory No Disease, Agnosia Brain Mild Memory Early despite intact No SymptomsobjectsChanges, sensory function) Loss No SymptomsExecutive function disturbance (e.g., Changes, Loss No Symptoms planning, organizing, sequencing, No Symptoms
abstracting)

Pre- deficits Mild Multiple cognitive Normal Amnesia (Memory loss) Cognitive symptomatic Aphasia (language disturbance) AD Apraxia (impaired ability Impairment to carry out motor activities despite intact motor

Definition of the dementia synd

AD
Mild, Moderate Mild, Moderate and Severe and Severe Impairment Impairment

These lead to functional decline

Disease Progression Disease Progression

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington DC: APA, 1994

Inability to choose proper clothing to wear

Inability to put On clothings

Requiring assistance in cleanliness in toileting

8 years average. Range 2-20 years

Peak Frequency of Behavioral Symptoms as Alzheimers Disease Progresses

100 Prevalence (% of patients)
Agitation

80 60 40 20 0 40
Suicidal ideation Accusatory Diurnal rhythm Irritability

Depression Social withdrawal Paranoia

Wandering
Aggression

Anxiety Mood change

Hallucinations Socially unacc. Delusions Sexually inappr.

30

20

10

10

20

30

Months Before/After Diagnosis

Jost BC, Grossberg GT. J Am Geriatr Soc. 1996;44:1078-1081.

AD: a progressive CNS disorder impairing patients ability to function

INCREASED SEVERITY
INCREASED BURDEN
Loss of speech, locomotion, consciousness; death

Stage 7 very severe

Stage 6 severe Stage 6 severe Stage 5 mod severe

Full-time care needed; institutionalised Can no longer care for self; incontinent, depressed Can no longer manage personal affairs; agitated, care needed Family and friends notice problems Mild function deficit forgetful No noticeable cognitive decline Normal
Years after onset

Stage 4 moderate
Stage 3 mild Stage 2 very mild Stage 1 appears normal

10

15

20

Definitions from the Global Deterioration Scale

Reisberg B et al., 1982

Progression of symptoms in typical dementia

BURDEN

Lovestone & Gauthier 2000

Will Cover the followings

Introduction to dementia The spectrum of cognitive dysfunction Evaluation of memory problems Management Non-pharmacological management Pharmacological management Whats in the future for dementia What about Delirium Conclusion

Steps in diagnosing dementia

History Physical examination Cognitive tests Perform brief cognitive tests Neuropsychological tests Non-cognitive tests Assessment of BPSD Assessment of ADL Screening co-morbid condition Establishing diagnoses Assessing severity and progression Neuroimaging EEG Biomarkers

Course of Aging, MCI and AD

Brain Aging AAMI / ARCD Brain Aging BrainAD MCI Mild

Cognitive Decline

Moderate
Clinical AD Moderately Severe Severe

Time (Years)

(Ferris, 4/03)

Differential Diagnosis of Dementia

Other dementias Frontal lobe dementia Creutzfeldt-Jakob disease Corticobasal degeneration Progressive supranuclear palsy Many others Dementia with Lewy bodies Parkinsons disease Diffuse Lewy body disease Lewy body variant of AD AD and dementia with Lewy bodies

Vascular dementias Multi-infarct dementia Binswangers disease

Vascular dementias and AD

AD

5% 10%

65%

5%

7% 8%

Small GW, et al. JAMA. 1997;278:1363-1371; American Psychiatric Association. Am J Psychiatry. 1997;154(suppl):1-39; Morris JC. Clin Geriatr Med. 1994;10:257-276.

Differential Diagnosis
Alzheimers disease
Stroke, Focal signs EPS, Visual hallucination

Behaviour, Language

Vascular dementia

Lewy body dementia

Frontotemporal dementia

Regional distribution of atrophy in the common dementias

Alzheimers disease Frontotemporal dementia Dementia with Lewy bodies Vascular dementia

predominantly parietal and temporal predominantly frontal and temporal as for AD, but with additional subcortical pathology vascular distribution

Executive functions

Praxia

Functional regions FTD AD

Language Memory

Perceptuospatial function

Differential Diagnosis: Top Ten

(commonly used mnemonic device: AVDEMENTIA) 1. Alzheimer Disease (pure ~40%, + mixed~70%, ? dLbd) 2. Vascular Disease, MID (5-20%) 3. Drugs, Depression, Delirium 4. Ethanol (5-15%) 5. Medical / Metabolic Systems 6. Endocrine (thyroid, diabetes), Ears, Eyes, Environ. 7. Neurologic (other primary degenerations, fronto-temporal
- Consider diffuse Lewy body dementia, Parkinson component)
8.
9. 10.

Tumor, Toxin, Trauma Infection, Idiopathic, Immunologic Amnesia, Autoimmune, Apnea, AAMI

Adapted from Yesavage, 1979

Co Morbidity issues
Multiple medical problems
Cumulative effect Poly pharmacy Acute illnesses Under assessment and treatment ..added to dementia in the equation

COMORBIDITIES DEMENTIA
Cognitive impairments Atypical presentation Poor reporting of co-morbidities

worsening

Excess morbidity

Under- or late diagnosis of comorbid conditions

Worsening of overall health status

Chronic Disease Model of AD

Preclinical phase Diffuse plaques Clinical phase

Neuritic plaques, NFTs, neuron and synapse loss

Antecedent biomarkers

Cognitive impairment Functional loss

Diagnosis

Genetic & environmental factors

Onset of symptoms

Death

Dementia in local services

UMMC Memory clinic (Geriatric) Hosp Seremban Memory clinic (Geriatric) Hosp Johor Bahru Memory clinic (Geriatric Psych) Hosp Kajang (Geriatric psych)

AD VaD

Mixed (ADVaD)
Other dementias

64% 17% 17% 2%

63% 29 % 8%

60% 24% 15%

62% 25% 15%

Database: Yau WK et al, Chin A-V,Yusoff S, Vengadasalam

Diagnostic Thresholds for Dementia

Dementia results from progressive neuronal deterioration, from minimal to extensive. Conventional diagnosis draws a line in its course, labeling one side as demented and the other not.

Threshold 1

Cognitive Abilities

Very Mild or MCI Mild

Threshold 2 Threshold 3

Moderate -Severe

Course of Dementia

Max 5 5 3

Markah pesakit Orientasi Masa Tahun, bulan, hari, tarikh, waktu (+/- 1 jam) Orientasi Tempat: Negara, Negeri, Bandar,Tempat (hospital/rumah), bilik (wad/klinik) Pendaftaran:Saya akan menguji ingatan awak. Sila dengar dengan teliti, tiga objek yang saya akan baca, iaitu, oren, kunci dan sikat. Sila sebut semula tiga objek tadi. Ingat betul-betul, kerana saya akan bertanya kemudian. Perhatian dan Pengiraan (sila guna salah satu kaedah) M-MMSE-7: Sila tolak 7 dari 100 dan teruskan. M-MMSE -3: Atau, tolak 3 dari 20 dan teruskan. M-MMSE-S: Atau, ejakan perkataan DUNIA dari belakang ke depan.

3 2 1 3 1 1 1

Ingat Kembali Sila sebut kembali 3 objek yang telah disebut tadi. Penamaan Namakan benda ini. (Pensel dan Jam Tangan) Ulangan Sebutkan Tidak mungkin dan cukup mustahil Arahan tiga peringkat: Ambil kertas dengan tangan kanan, lipat setengah dan letakkan atas lantai/meja. Pembacaan: Baca dan lakukan ..TUTUP MATA ANDA Penulisan: Tulis satu ayat yang lengkap. Penyalinan

Jumlah

Clock Drawing Test (CDT)

10 minutes past 11 12

Closed circle

= 1
10

11

All 12 numbers present = 1 2 12 numbers in correct position Hands in correct position = 1 9 = 1 ___ 4

.
8 7 6 4 5

Low score indicates impairment. Cut-off score is subjective & arbitrary. Clinical judgment must be applied.

Nolan KA 1994

Malay Mini Mental State Examination

M-MMSE-7 M-MMSE-3 (n=300) (n=160) Optimal cut-off Sensitivity Specificity PPV 21/ 22 88.5 75.3 53.7 18/19 97.1 90.0 57.6 M-MMSE-S (n=145) 17/ 18 97.7 93.3 62.5

NPV
AUC

95.5
0.9

99.2
1.0

100.0
1.0

Cut off values and accuracy of the different versions of the Malay MMSE
Ibrahim et al, 2009

Diagnosing Alzheimers disease

8090% accuracy

Will Cover the followings

Introduction to dementia The spectrum of cognitive dysfunction Evaluation of memory problems Management Non-pharmacological management Pharmacological management Whats in the future for dementia What about Delirium Conclusion

Mechanism of cognitive impairment

2 mechanism:
Acetycholine deficits

NMDA receptor antagonist

Reduces severity of cognitive symptoms Improved Quality of Life Decreased caregiver burden

Above - For Mild to Severe disease Stabilise pts symptoms for a period of 1-3 years but without modifying progression of the disease
Ezio Giacobini and Robert E becker, One Hundred Years after the Discovery of Alzheimers Disease. A Turning Point for Therapy? Journal of Alzheimers Disease 12 (2007) 37-52 IOS Press

Treatment Outcomes in Alzheimers Disease

Cure
Functional ability

Maintenance of function Slowing of disease progression Symptomatic benefit Natural Progression

Time
(Ferris, 8/03)

Treatment

Clinical Disease Progression

Mild
30 25 MMSE Score 20 15 10 5 0 0 1 2 3 4 5 6 Years From Diagnosis 7 8 9
Diagnosis
Loss of Functional Independence Behavioral Problems Nursing Home Placement Death Cognitive Symptoms

Antidepressant Moderate CHEi CHEi Memantine

Severe

CHEi+/-Memantine Atypical Antipsychotics CHEi+/-Memantine Atypical Antipsychotics

Reprinted from Clinical Diagnosis and Management of Alzheimers Disease, H Feldman and S Gracon; Alzheimers Disease: symptomatic drugs under development, pages 239-259, copyright 1996, with permission from Elsevier.

Dementia CPG 2nd Ed

Mdm LKM, mom of senior radiographer in Hosp Seremban

1st notice memory problem in 1995, forgotten her medications, content of conversation s over phone and things around her. Still driving and MMSE 26/27 2001 Hiding things (family found rotten buns), forgotten to lock door. 2002. Worst. Agnosia, lost way home, cant communicate with others well. Manages ADL but stopped IADL. Treated with Rivastigmine. Till 2009 - on and off UTI, incontinence. Daughter come for medications. Cant do MMSE. Hardly talk. Admitted in 2009, stormy progress. DNR discussed. Needed RT feeding. Bedridden mostly. Bedsore dressed by daughter. Had stopped talking all together. August 2009 started memantine. RT off. Become more chatty. Ask maid to move aside as she want to watch TV, started walking back again with 2 and bed sore settled.

H Cayton, N Graham, J Warner, Alzheimers at your fingertips, 1997

Barbara Sherman, Dementia with dignity. A Handbook for Carers, Revised Ed1994

Amyloid Generation
Neuritic Plaque

NFT

Excitotoxicity

Oxidation

Inflammation

Cell Death
Cholinergic Deficit
Cummings 2004

Disease-Modifying Strategies
anti-inflammatories antioxidants immunotherapy neuroprotectants amyloid binders

secretase modulators -secretase

APP

-secretase

inflammation oxidative stress excitotoxicity direct toxicity

Neuron death

Primary Prevention Trials in AD

Study ADAPT Agent
Naprosyn Celecoxib

Enrollment criteria
Cognitively screened, >70, 1st degree relative with AD

No enrolled
2496 enrolled

Duration
7-10yrs

Currently active
Tx stopped

Outcome measures
Conversion Study to dementia and cognitive decline

Result
No result yet Neg - 2008

GEM

Gingko Biloba extract

Asymptomatic, >75

5000

5-7 yrs

Active

Inc of dementia or cognitive decline Cognitive test

No result yet Neg - 2009 1 test improved

HERS Heart Protection Study Heart Protection Study PREADVISE

Estrogen and medroxyprogest erone Vit E, C, and beta carotene

Asymptomatic women, mean age 67 Asymptomatic with CVS rsik factors, age 40-80 years Asymptomatic with CVS rsik factors, age 40-80 years Asymp men, >60 yrs

1063

4.2 yrs

Completed

20536

5 yrs

Completed

TICS and incident dementia TICS and incident dementia Incident dementia and cognitive tests

No difference btwn tx and untx arm No difference btwn tx and untx arm No result yet Maybe in 2012 / 2013

Simvastatin

20536

5 yrs

Completed

Selinium, Vit E

10,400

12 yrs

Completed

Sano M, Current Concept in the Prevention of AD, Cns spectrum 2003:8: 846-853

Primary Prevention Trials in AD Cont ..

Study WHI-PERT
Agent Enrollment criteria Women without dementia, ages 65-80 No enrolled 4532 Duration Currently active completed Outcome measures Incident dementia, MCI and 3MS score Result

Estrogen n medroxyprogest.

4 yrs

Treated subjects had elevated risk of dementia and worse 3MS score Treated subjects had elevated risk of composite MCI/dementia and worse 3MS score Not yet available

WHI-ERT

Estrogen.

Women without dementia, ages 65-80

2497

5 yrs

completed

Incident dementia, MCI and 3MS score

GUIDAGE

Gingko Biloba extract

Subjective memory complaints, >70 Asymptomati c, >65 yrs

2600

4 yrs

Ongoing

Incident dementia

PHS-II

Vit E, Folate, beta carotene

10, 000

9yrs

Ongoing

Telephone cognitive Testing

Not yet available

Sano M, Current Concept in the Prevention of AD, Cns spectrum 2003:8: 846-853

CONNECTION trial, MC RCT, phase 3, of almost 600 patients with AD, result negative, after 6 months of treatment.- mac 2010

CONCERT trial, a 12-month study testing latrepirdine in patients with mild-to-moderate AD who are taking donepezil;
CONTACT and CONSTELLATION trials, 6-month trials of latrepirdine in patients with moderate-tosevere AD also taking donepezil and memantine, respectively.

The etiology of Alzheimer's disease remains elusive, although considerable progress has been made in understanding its biochemical and genetic mechanisms.

Will Cover the followings

Introduction to dementia The spectrum of cognitive dysfunction Evaluation of memory problems Management Non-pharmacological management Pharmacological management Whats in the future for dementia What about Delirium Conclusion

100 years of AD- major milestone

Tacrine trials amyloid sequenced Role of NFTs and tau Presenile Dementia= Senile Dementia=AD Structures of tangles and plagues determined Neuritis plagues contains amyloid protein

Age of genetics APP, presenilin 1 and 2 mutation APOE4 E4 susceptibility Amyloid cascade hypothesis of AD

Presenile dementia Rare Young onset

Separation of Senile Dementia fr VaD and Depression

Cholinergic hypothesis of AD AD recognised as major health issue

CHEIs approved Role of glutamate approved Memantine approved

1950s

1960s

1970s

1980s

1990s /2000s

Slides fr Professor Roy Jones Director Research Institute for Care of Elderly,Bath presented at the 11th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy March 24 27, 2010Geneva

THE FUTURE
1.

Better detection - GPs, public Better diagnosis - biomarkers - imaging amyloid and tangles Disease prevention / delay Disease cure? - eg vaccination Better support

2.

3. 4.

5.

http://clinicaltrials.gov/ct2/results?term=DEMEN TIA http://www.alzforum.org/dis/tre/drc/default.asp http://www.nia.nih.gov/Alzheimers/Publications/ ADProgress2008/rapid/ongoing1.htm

Ongoing NIA-Funded AD/MCI Prevention and Treatment Clinical Trials, as of November 2009
Page last updated Jan 12, 2010 Trial Name Principal Intervention Investigator
Population

Cardiovascular
ACCORD-MIND (Action to Control Lenore Launer Cardiovascular Risk in Diabetes/Memory in Diabetes)* Effects of Simvastatin on CSF AD Cynthia Carlsson Biomarkers ESPRIT (Evaluating Simvastatins Cynthia Carlsson Potential Role in Therapy) SPRINT-MIND (Systolic Blood Lawrence Fine Pressure Intervention Trial-MIND)* Intensive glucose, blood pressure, and lipid management Simvastatin People ages 40-79 with type 2 diabetes mellitus People ages 45-65 at high risk of AD (family history, APOE 4)

Simvastatin

People ages 35-69 at high risk of AD (family history) Blood pressure lowering Adults age 55 years or older to <140 mm Hg versus with systolic blood pressure <120 mm Hg of 130 mm Hg or higher, history of cardiovascular disease, high risk for heart disease Simvastatin Cognitively normal people ages 45-64

Statin Effects on Beta-Amyloid Gail Li and Cerebral Perfusion in Adults at Risk for AD

http://www.nia.nih.gov/Alzheimers/Publications/ADProgress2008/rapid/ongoing1.htm

Ongoing NIA-Funded AD/MCI Prevention and Treatment Clinical Trials, as of November 2009
Trial Name

Alzheimers Disease: Potential Benefit of Isoflavones ELITE (Early versus Late Intervention with Estradiol)

Healthy early (less than 6 years) or late (10 years +) menopausal women KEEPS-CA (Kronos Early Sanjay Asthana Oral conjugated Healthy perimenopausal Estrogen Prevention Study equine estrogen (CEE women ages 42-58 Cognitive and Affective or Premarin)and Study)* transdermal 17estradiol (tE2) Raloxifene for Women with Victor Raloxifene (selective Older women with AD Alzheimer's Disease Henderson estrogen receptor modulator or SERM) SMART (Somatotrophics, Michael Vitiello Growth hormone People with MCI and Memory, and Aging releasing hormone healthy older adults ages Research Trial) (GHRH) 55-80 Testosterone Monique Testosterone Older men with MCI and Supplementation in Men with Cherrier low testosterone MCI http://www.nia.nih.gov/Alzheimers/Publications/ADProgress2008/rapid/ongoing1.htm

Page last updated Jan 12, 2010 Principal Intervention Investigator Hormones Carey Gleason Novasoy (soy isoflavones phytoestrogens) Howard Hodis 17-estradiol

Population

People with AD

Ongoing NIA-Funded AD/MCI Prevention and Treatment Clinical Trials, as of November 2009 Cont

Other Interventions
AAV-NGF Gene Delivery in Alzheimers Disease fMRI Activation in Mild Cognitive Impairment GAP (Gammaglobulin Alzheimers Partnership)

Paul Aisen Michela Gallagher Norman Relkin

Nerve growth factor (NGF) gene delivery Levetiracetam Immune globulin intravenous (IVIg), passive immunization Thalidomide

People with AD People with MCI People with AD

Study on Thalidomide as BACE1 Inhibitor in Alzheimers Disease

Yong Shen

People with AD

http://www.nia.nih.gov/Alzheimers/Publications/ADProgress2008/rapid/ongoing1.htm

AD treatment 2010 and Beyond

2010 ACHEIs, Memantine, Combination Other cognitive enhancers (Dimebon?, 5HT6, H3) Improved and Early Diagnosis 2020

Patient segmentation(genetics)

Disease modifying therapies

Community-wide preventive initiatives (diet, exercise)
Slides fr Professor Roy Jones Director Research Institute for Care of Elderly,Bath presented at the 11th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy March 24 27, 2010Geneva

Overlap between Alzheimers disease and vascular dementia

Cholinergic deficit

AD

Probable

Possible

Mixed

Possible Probable

VaD

Amyloid plaques Genetic factors Neurofibrillary tangles

Mixed AD/CVD
Amyloid plaques Genetic factors Neurofibrillary tangles Stroke/TIA Hypertension Diabetes Hypercholesterolemia Heart disease

Stroke/TIA Hypertension Diabetes Hypercholesterolemia Heart disease

Kalaria RN, Ballard C. Alzheimer Dis Assoc Disord. 1999;13(Suppl 3):S115-123.

Hypertension

A systematic review & meta-analysis of 4 studies: non-sig: RR =0.8, 95%CI 0.6 - 1.0 Hypertension in the Very Elderly Trial Cognitive Function Assessment (HYVETCOG) Non-sig: HR 09, 95%CI 07 - 11 These data -combined in meta-analysis with other placebo-controlled trials of a/HPT rx , favoured treatment (HR 09, 95%CI 08 to 10, p=0045).[46] Level I, fair

Hypertension in the Very Elderly Trial Cognitive Function Assessment (HYVET-COG)

Recommendation Hypertension, occurring at mid-life (40-60 years) is a risk factor for dementia and should be appropriately treated. (Grade A)

Diabetes

Swedish HTA report - evidence linking diabetes mod strong.[47] Level 1, good A recent meta-analysis of 15 prospective cohort studies diabetes was associated with a 47% increased risk for all dementia, 39% for Alzheimers dementia, >2-fold risk for vascular dementia, (community dwelling )

Diabetes mellitus is a modifiable risk factor for the development of dementia and should be appropriately treated. (Grade C)

Lifestyle Risk Factors

Smoking

Alcohol
Obesity Head Injury Exercise Education / Mental stimulation Social network

LEARNING AND LONGEVITY OF THE BRAIN NUN

The Nun Study is a longitudinal study of aging and Alzheimer's disease funded by the National Institute on Aging. 678 American members of the School Sisters of Notre Dame religious congregation who are 75 to 106 years of age.

Study

Subcortical infarction Importance of education Importance of mood Head size

http://www.mc.uky.edu/nunnet/ Snowdon et al. JAMA 1997; 277: 813-7

ALCOHOL & DEMENTIA

Several studies - light to moderate alcohol consumption assoc. with a lower risk of Dementia AND AD Rotterdam study1 - 45% < risk of any dementia in those who drink 1-3 drinks / day, compared to non drinkers
1. Ruitenberg et al. Lancet 2002; 359:281-6

Obesity

Several prospective studies found an association between raised body mass index in mid life and an increased risk of dementia and AD. A systematic review of 4 cohort (n=22,861) F/U 20 years = significant risk. [59] Level II-2, fair A meta-analysis of 7 prospective studies found moderate association Obesity and incident AD was 1.8 (95% CI 1.0 to 3.3) Obesity and VaD was 1.7(95% CI 0.5 to 6.3)
[60] Level II-2, good

Recommendation Obesity is a modifiable risk factor and maintenance of normal body mass index is recommended. (Grade C)

PHYSICAL ACTIVITY
Women Who Walk project1
5,925 woman over age 65 no cognitive impairment at baseline follow up 6-8 years
25 20 15 10 5 0

NEW COGNITIVE IMPAIRMENT (%)

ACTIVITY QUARTILE
1. Yaffe et al. Arch Intern Med 2001; 161:1703-8

Will Cover the followings

Introduction to dementia The spectrum of cognitive dysfunction Evaluation of memory problems Management Non-pharmacological management Pharmacological management Whats in the future for dementia What about Delirium Conclusion

Acute Delirium
Confused
Restless Pulled

out

CBD

The older patient with delirium :

Associated

with

longer hospital stays, increased mortality

hospitalized percent, [2] 1-year

patients with delirium : 22 - 76

mortality rate : 35 - 40 percent. [3]

2. Am J Psychiatry 1999;156:Suppl:1-20 3. Moran Aust J Hosp Pharm 2001;31:35-40

quiet

patient non-demanding good patient

Last

cubicle

ClassificationLipowski
1.

Hyperactive-hyperalert (agitated) Hypervigilance, agitation Hyperactivity Hallucinations Vs schizophrenia Mixed delirium

2.

3.

Hypoactive-hypoalert (somnolent) lethargic & quiet overlooked in busy ward respond appropriately monosyllable answers withdrawn, drift off to sleep VS Depression Uncooperative

JAGS MARCH 2006VOL.54,NO.3 DELIRIUM SUBTYPES IN THE CRITICALLY ILL 481 J Am Geriatr Soc 54:479484, 2006.

Delirium in the Hospitalised Elderly Juli A Moran, Michael I Dorevitch Aust J Hosp Pharm 2001; 31: 35-40. 3. Inouye SK. The dilemma of delirium: clinical and research controversies regarding diagnosis and evaluation of delirium in hospitalized elderly medical patients. Am J Med 1994; 97: 278-88. FSLee Geriatrics HKL May06

89

Number of precipitating factors

Interaction

FSLee Geriatrics HKL May06

Mx of delirium in hospital
Prevention
Early diagnosis Search and treat precipitating factors Supportive measures, if necessary medication

Delirium in the Hospitalised Elderly Juli A Moran, Michael I Dorevitch Aust J Hosp Pharm 2001; 31: 35-40

Detection
Lewis

and colleagues11 N= 385 patients, prevalence of 10% - CAM. detection rate of delirium by ED physicians based on chart review 17%.
11. Lewis LM, Am J Emerg Med 1995; 3:142-5.

CAM (Confusion
Assessment Method)
1. Acute change & fluctuation in mental status and behavior AND 2. Inattention AND EITHER 3. Disorganized thinking OR 4. Altered consciousness
Inouye SK et al. Ann Intern Med 1990;113:941-948.

UTI For rehab

Multicomponent Mx of Delirium Symptoms

www.health.vic.gov.au/acute-agedcare

Features Onset

Delirium Acute or subacute onset (hours or days) Frequent and rapid fluctuations (hours) Rapid functional decline Conscious level Attention markedly reduced

Alzheimer's disease Insidious (usually several years) Slow changes (months)

Relatively slow functional decline Attention reduced only in severely affected patients Arousal increased or decreased Arousal usually normal Psychotic Delusions (if present) fleeting Delusions (if present) often symptoms consistent Hallucinations common often visual Hallucinations infrequent, visual, and auditory Motor features Abnormal movements such as Abnormal movements often tremor or myoclonus common absent Psychomotor activity increased or Psychomotor activity usually decreased normal Underlying Symptoms and signs usually present Symptoms absent physical illness Day and night Often disturbed with a marked No clear day and night rhythm. rhythm increase in symptoms during the Symptoms are more consistent night

Prevention
1. 2.

3.
4. 5.

6.

Cognitive impairment Sleep deprivation Immobility Visual impairment Hearing impairment Dehydration

Delirium: Summary :
Delirium is under diagnosed. Hypoactive delirium
More

difficult to diagnose Poorer outcome

Management :
Early

Diagnosis Multifactorial approach Prevention

99

Will Cover the followings

Introduction to dementia The spectrum of cognitive dysfunction Evaluation of memory problems Management Non-pharmacological management Pharmacological management Whats in the future for dementia What about Delirium Conclusion

Conclusion 1

Normal changes = more forgetful & slower to learn MCI Mild Cognitive Impairment no functional decline

Some eventually develop dementia

Dementia = Chronic thinking problems in > 2 areas

Vascular dementia - covers the whole spectrum of cerebrovascular disease and cognition
DLB sits on the interface between AD, delirium and Parkinsons disease FTD dementia without the dementia, revealing how the frontal lobes govern personality and theory of mind Seek cause and treat urgently

Delirium =Rapid changes in thinking & alertness

Two elderly ladies had been friends for many decades. Over the years they had shared all kinds of activities and adventures. Lately, their activities had been limited to meeting a few times a week to play cards. One day they were playing cards when one looked at the other and said, "Now don't get mad at me....I know we've been friends for a long time.....but I just can't think of your name! I've thought and thought, but I can't remember it. Please tell me what your name is." Her friend glared at her. For at least three minutes she just stared and glared at her. Finally she said, "How soon do you need to know?"

Conclusion 2

AD is an expensive illness in human and economic terms for patients, their caregivers, and society. Diagnosis is often not made, especially in early and mild AD; clinical nihilism can interfere with initiating or sustaining treatment. Cholinesterase inhibitors and NMDA receptor antagonists attenuate symptomatic decline Early treatment pays off; delaying treatment has long-term consequences.

Therapeutic Strategies
Latency
Traumatisms Vascular risk factors

Detection

Symptoms Induction
Genetic/hereditary

Pathogenesis

Disease

Primary Prevention
?Vaccine ?Estrogen ?Ginkgo

Symptomatic Secondary Treatment Prevention Cholinergic replacement (Mild cognitive therapy Impairment)
?Antioxydants ?Anti-inflammatories ?Neurotrophic factors ?Estrogens ?Others

Vascular Prevention

Mind your Mind

Mind your brain cognitive stimulation Mind your body exercise Mind your head protect head Mind your habits smoking Mind your health check BP, cholesterol Mind your diet antioxidant, polyphenol Mind your social activities - engagement

Prof Henry Brodaty; Dementia: Can it be prevented? Alzheimers Australia: Position Paper 6 August 2005