Rusdi Lamsudin Department of Neurology Faculty of Medicine Indonesian Islamic University Yogyakarta, INDONESIA

DEMENTIA

EPIDEMIOLOGY, ECONOMIC-IMPACT AND CLINICAL’S ASPECT

Rusdi Lamsudin

Department of Neurology Faculty of Medicine

Indonesian Islamic UniversityYogyakarta, INDONESIA

Overview

Epidemiology Economic Impacts Definition Clinical presentation Diagnosis Differential Diagnosis Etiology Workup Non-pharmacologic Treatments Drug Treatments Terminal Care

EPIDEMIOLOGY

Epidemiology

Dementia affects 17–25 million people worldwide Estimated 4 million in the US and an estimated

800,000 people in the UK [Ritchie, 1995; Keefover, 1996].

It affects predominantly elderly people, The prevalence of dementia in people over the age of 65 is 5% and in people over 80, it is 20%.

It has been estimated that 26% of women and 21% of men over the age of 85 have some form of dementia, of whom approximately 50% have Alzheimer’s disease (AD) [Melzer, 1997].

Epidemiology

In case of AD:- Age specific prevalence rates almost double

with every additional 5 years of age from 1% of 65, rising to about 8-10% at age 80 and 30-40%at age 90

- African-Americans and Hispanics may have a higher risk than Caucasians-Americans. It also occurs less frequently in Asians than Americans

Growth of numbers of people with dementia

The World Alzheimer Report (2009) estimated:

35.6 million people living with dementia worldwide in 2010

Increasing to 65.7 million by 2030

115.4 million by 2050

Economic Impact

Worldwide cost of dementia

The societal cost of dementia is already enormous.

Dementia is already significantly affecting every health and social care system in the world.

The economic impact on families is insufficiently appreciated.

The total estimated worldwide costs of dementia are US$604 billion in 2010.

These costs are around 1% of the world’s GDP

0.24% in low income1.24% in high income

Worldwide costs of dementia

The World Alzheimer Report (2010) estimated that:

If dementia care were a country, it would be the world’s 18th largest economy

Definition

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Definition

a syndrome characterized by progressive decline of intellectual ability from a previously attained level

the decline in mental inability usually involves variable deterioration in

- speech - memory- judgment - mood

without alteration of consciousness

Definition Multiple Cognitive Deficits:

Memory dysfunction especially new learning, a prominent early

symptom At least one additional cognitive deficit

aphasia, apraxia, agnosia, or executive dysfunction

Cognitive Disturbances: Sufficiently severe to cause impairment of

occupational or social functioning and Must represent a decline from a previous level of

functioning

Clinical Presentation

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Clinical Presentation

onset of dementia it is usually insidious

dementia is often progressive (degenerative disease) but may be static (post-traumatic brain injury)

initial presentation may include slight forgetfulness, attention and concentration deficits, and increasing repetitiousness or inconsistencies in usual behavior

later presentation may display impaired judgment, inability to abstract or generalized, and personality change with rigidity, perseveration, irritability, and confusion; affective disturbances may be prominent with loss of personality and self-care

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Impairment of 2 or more cognitive domain

Memory loss

Language

Abstract thinking & Judgment

Praxis (learned motor behavior)

Spatial processing

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1

4

7 Social conduct

Personality65

Risk Factors for Dementia

Gender: male Age: 60-70 years Prior stroke Hardening of the

arteries Heart disease High blood

pressure Diabetes

• Cholesterol problems

• Atrial fibrillation• Smoking• Education• Race• Family history

(CADASIL-cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy )

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Most common causes of dementia

• Alzheimer’s disease• Vascular dementia• Lewy body dementia• Frontotemporal dementia

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Established risk factors for dementia

• Age• Female sex• Head trauma• Low level of education

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• Coronary artery disease

• High dietary saturated

fat and cholesterol• Serum cholesterol• Hyperhomocysteine

mia

• Smoking• Diabetes

mellitus• Hypertension• Apolipoprotein

E status

All these are vascular risk factors!

Risk factors for dementia

Diagnosis and Diffeerential Diagnosis

Differential Diagnosis:TopTen (commonly used mnemonic device: AVDEMENTIA)

1. Alzheimer Disease (pure ~40%, + mixed~70%)

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, etc.)

8. Tumor, Toxin, Trauma9. Infection, Idiopathic, Immunologic10. Amnesia, Autoimmune, Apnea, AAMI

Comparison of the Clinical Features

Dementia Depression Delirium

Insidious/slow and often unrecognized; depends on cause

Coincides with major life changes; often abrupt, but can be

gradual

Sudden/abrupt; depends on cause; often at twilight or in

darkness

Clinical Features: ONSET

COURSE, PROGRESSION, ATTENTION, MEMORY, THINKING


Neurologic Diseases Associated with Intellectual DysfunctionDISEASE PHYSICAL SIGNS CLINICAL FEATURES

Creutzfeldt-Jakob Myoclonus , cerebellar signs, Subacute course; EEG has specific abnormalities,

eye movement abnormalities brain biopsy diagnostic

Huntington's disease Choreiform movements, Often positive family history; caudate atrophy

corticospinal signs by CT or MRI

Multiple sclerosis Brainstem signs, optic atrophy, Usually long-standing disease; episodic illness

corticospinal signs with remissions; often extensive white matter

abnormalities by MRI

Wilson's disease Extrapyramidal signs , hepatic Onset in adolescence or young adult life, dysfunction, Kayser-Fleischer psychiatric disordersrings

Progressive Failure of vertical downgaze, Eye movement abnormalities; differentiate fromsupranuclear extrapyramidal signs Parkinson's disease; unresponsive or onlypalsy transiently responsive to levodopa

* = invariably present; all other physical signs are neither invariably present nor pathognomonic.

Etiologic Diagnosis of Progressive Dementias in Adults Neurodegenerative

Diseases Alzheimer’s disease Parkinson’s disease Diffuse Lewy body disease Progressive supranuclear palsy Multisystem atrophy Huntington’s disease Frontotemporal dementias – e.g. Pick’s disease

Structural Disease or Trauma Normal pressure hydrocephalus Neoplasms Dementia pugilistica

Vascular Disease Vascular dementia Vasculitis

Heredometabolic Disease Wilson’s disease Other late-onset lysosomal storage diseases

Etiology contd.

Demyelinating or Dysmyelinating Disease Multiple sclerosis

Infectious Disease Human immunodeficiency virus, type 1 Tertiary syphilis Creutzfeldt-Jakob disease Progressive multifocal leukoencephalopathy Whipple’s disease Chronic meningitis – e.g. Cryptococcal

Etiology contd.

Acute brain dysfunction characterized by: Global symptoms (affecting both cerebral

hemispheres) including impairment of consciousness and attention

Primary physiological changes with potential for reversibility

‘waxing and waning’ symptoms – usually worse in evening

Life-threatening conditions underlying the syndrome

DELIRIUM

Symptoms of Delirium

Common symptoms of a delirium include: Waxing and waning levels of

consciousness Poor attention and disorientation Disturbed memory (long and short term) Psychosis Sleep dysregulation Fearfulness with agitation and

aggression Seriously impaired insight and judgment

Epidemiology of DeliriumEpidemiology of Delirium

Very Common - 10-15% med/surg inpatients (30%+ if elderly)

30% of Adult Burn Patients 80%of delirious patients have pre-

existing dementia Predisposing Factors:

old age, postcardiotomy, s/p burns prexisting brain damage drug withdrawal states AIDS

Causes of Delirium

Often multifactorial Infections, trauma, brain diseases Cardiac diseases, lung disease,

hypoxia, hypoglycemia Toxins, or intoxications Medication effects Substance withdrawals (e.g. DTs) Endocrinopathies In elderly dementia patients: UTI,

dehydration and pneumonia are the most common causes

DELIRIUM - TREATMENTDELIRIUM - TREATMENT

• Must look for medical cause(s) and treat• Symptoms can be helped by

antipsychotic drugs such as haldoperidol or risperidone (especially psychosis, agitation)

• Consider anticholinesterases for anticholinergic delirium

• Comfort measures include reorientation strategies, reducing stimulation, frequent reassurance

General rules of thumb: Delirium Dementia

acute chronic

reversible irreversible

physiological structural

primary attention primary memory

deficits deficits

Delirium and dementia can coexist; in fact delirium is very common in demented patients

Delirium vs Dementia(summary)

Work-up


Workup

History Physical Examination Laboratory studies


History - etiology

the most important component of the initial evaluation

adequate history with help of a family member is critical description of

cognitive, memory, and behavior problems effect on daily life - difficulty with driving, work, or family

relationships details on temporal course of illness

chronic progressive (Alzheimer or other neurodegenerative

disease) stepwise (multi-infarct) static (traumatic injury, episode of severe hypotension)


History - treatable causes Vascular dementia - presence of cardiovascular risk

factors (smoking, HTN, chol, diabetes) Normal pressures hydrocephalus - triad of dementia,

gait, incontinence with a prior history of meningitis or subarachnoid hemorrhage

Mass lesion - history of head trauma, unexplained focal neurologic deficit, unilateral headache worsening over time

Parkinson’s disease - resting tremor and rigidity Wilson’s disease - hepatocellular disease and dementia HIV and neurosyphilis - high-risk sexual behavior hereditary - family history dementia, Down’s syndrome,

psychiatric disorders


History - treatable causes B12 deficiency - previous gastric surgery

B12, thiamin, niacin deficiency - inadequate nutrition, alcohol abuse

medications - opiates, sedative-hypnotics, analgesics, anticholinergics, anticonvulsants, corticosteroids, centrally acting anti-hypertensives, psychotropics

symptoms of hypothyroidism, pituitary insufficiency occupational history - exposure to toxic substances

(aniline dyes, heavy metals)

Diagnostic Criteria For Dementia Of The Alzheimer Type (DSM-IV, APA, 1994)

A. Multiple Cognitive Deficits1. Memory Impairment 2. Other Cognitive Impairment

B. Deficits Impair Social/Occupational

C. Course Shows Gradual Onset And Decline

D. Deficits Are Not Due to:1. Other CNS Conditions2. Substance Induced Conditions

E. Do Not Occur Exclusively during Delirium

F. Not Due to Another Psychiatric Disorder


Mental Status Examination

Examination should be geared to both the detection of focal lesions and to signs of general brain dysfunction immediate memory testing (three object recall, recite

digits forward and backward, recall a short story) remote memory testing (recall of historical events,

family milestones, or recent local or international news)

reproducible drawings discern similarities among objects decision-requiring tasks (finding a stamped letter or

seeing a fire in a theater)


Mini-Mental Status Tests

Score

Recall:

3 Ask for 3 objects repeated above. Give one point for each. Language:

2 Name a pencil and watch (2 points).

1 Repeat the following: "No ifs ands or buts."

3 Follow a 3-stage command: "Take a paper in your right hand:

fold it in half, and put it on the floor." (3 points).

1 Read and obey the following: "Close your eyes."

1 Write a sentence.

1 Copy design.

Total Score: [ ] Maximum Score: 30


Physical and Neurologic Examinations Check for focal evidence of neovascular risk

factors - carotid bruits, signs of alcoholism, hepatocellular injury, renal insufficiency, other systemic illnesses

specific neurologic abnormalities frontal lobe release signs (grasp, suck, snout, root) visual field cut and extraocular movement limitations abnormal pupillary reactions extrapyramidal features (carditis dyskinesis, tumors,

asterixis, Korea, monoclonal disc, it) sensory deficit and gait disorder


Screening Laboratory Studies

1. Complete blood count and sedimentation rate 2. Chemistry panel (electrolytes, calcium, albumin,

BUN, creatinine, transaminase) 3. Thyroid-stimulating hormone (TSH) 4. VDRL test for syphilis 5. Urinalysis 6. Serum B12 and folate levels

7. Chest x-ray 8. Electrocardiogram 9. Head computed tomography (CT)


Neuroimaging

Head CT or MRI is appropriate in the presence of1) history suggestive of a mass lesion2) focal neurologic signs or symptoms3) dementia of abrupt onset4) history of seizures5) history of stroke

MRI with gadolinium contrast enhancement is superior to CT for the diagnosis of multi-infarct dementia and problems referrable to the posterior fossa


Other Ancillary Studies

Lumbar puncture routine LP for initial evaluation of dementia

is not justified may be indicated when other clinical

findings suggest an active infection or vasculitis and as part of the evaluation of normal pressure hydrocephalus

sugar, protein, cell count, cultures, gamma globulins, the serology for stiffness should be obtained



Electroencephalogram (EEG) usually normal or with nonspecific rhythm slowing indicated in patients with episodic altered

consciousness and in whom seizures may be suspected

may occasionally raise suspicion of a particular etiology: focal, delta slowing is seen with tumor unilateral attenuation of voltage may suggest an

extracranial mass such as subdural hematoma excessive beta activity may be consistent with drug

ingestion Creutzfeldt-Jakob disease has a highly specific EEG pattern



Formal neuropsychologic evaluation appropriate for more specific information when the

diagnosis is in doubt also helpful in providing additional information about

the nature of impairment following focal brain injury

Speech analysis may improve patient and family communication with

therapy

Formal psychiatric assessment may be desirable if depression in addition to

dementia is suspected


Studies of Limited or Uncertain Utility Cerebral blood flow and metabolism measurements

PET and SPECT scans have no routine use at present

Brain biopsy rarely justified for non-neoplastic or noninfectious diseases Progressive multifocal leukoencephalopathy or Creutzfeldt-

Jakob disease is diagnosed by biopsy

Noninvasive neurovascular studies (carotid ultrasound, Doppler flow studies) if MRI or CT demonstrates infarction, or clinical course or physical examinations is suggestive of

cerebralvascular disease

Treatment

General Treatment Principles For Dementia Treatment Of Underlying

Disease Process (Primary Treatment)

Management Of Behaviors and Symptoms (Secondary Treatment)

Caregiver Support and Education

Primary Treatment Strategies(for progressive dementias)

Primary Treatment Strategies(for progressive dementias) 1. Prevention Identify risks and mitigate Develop neuroprotective strategies for those at risk

2. Slow or halt progression of illness Understanding pathophysiology leads to treatment ideas 5 year delay in onset ---> 1/3 decrease in prevalence Delaying institutionalization by 1 month saves $1.2 billion/yr

3. Reverse symptoms Compensate through augmentation of remaining neurons or

other systems Reversal of destructive processes & regeneration of tissue


Symptomatic Management and Counseling

Improving mental functioning

Management of confusion and agitation

Maintaining the patient at home

Risk factor reduction and attention to underlying etiologies


Improving Mental Functioning

no established treatment for Alzheimer’s disease or for patients with multi-infarct dementia

findings of degeneration of cholinergic neurons and depletion of choline-acetyl transferase in Alzheimer's disease have led to attempts at improving cholinergic transmission lecithin supplements (dietary choline repletion) tacrine (a centrally active, reversible cholinesterase

inhibitor) There is no evidence to support the use of: restorative

therapy with nerve growth factor, protective therapy with antioxidants, preventive therapy with drugs that inhibit beta amyloid formation, and “cerebral vasodilators” (papaverine, dihydroergotoxine) to improve memory


Management of Confusion and Agitation The chronic use of sedatives and psychoactive

agents in the confused patient should be avoided unless persistent extreme agitation hampers care

The lowest possible doses should be used and for the shortest time possible thioridazine (10 to 25 mg qhs) haloperidol (0.5 to 1 mg bid or tid )

often a first choice in the setting of delusions and hallucinations; must be careful to avoid long-term use because of the risk of inducing tardive dyskinesia


Management of Confusion and Agitation Avoid regular use of sedative/hypnotic agents

for sleep Beta-blocking agents and anticholinergics may

exacerbate confusion Patients with depression may improve with a

tricyclic compound with low anticholinergic side effects

- desipramine (25 to 50 mg qhs) A recent study of nursing home patients

demonstrated substantial improvement in many patients when chronically prescribed psychotropic drugs were discontinued or reduced in dose


Maintaining the Patient at Home

An important task is helping the family maintain and care for the patient at home

The goal is to sustain the highest level of function possible: facilitate and promote an orderly home situation regular routine use of calendars, television,

newspapers, and other means of orientation limit the use of potentially dangerous appliances provide convenient toilet facilities advice against driving when early impairment of

judgment and spatial concepts is present


Maintaining the Patient at Home

Families can often find help in local support groups, day care and group therapy services, and social service agencies

When care at home begins to exhaust and strain the family, sensitive counseling can do much to help a family cope with the difficult decision regarding institutionalization

some dementing diseases are infectious (eg, HIV infection) and that the bodily fluids and tissues of such patients require special handling to avoid transmission. It is particularly important to emphasize when home care is rendered by lay persons


Risk factor reduction and attention to underlying etiologies

Central to an effective outcome :

control of cerebrovascular risk factors as hypertension, diabetes mellitus, smoking , hyperlipidemia , and coronary artery disease

endarterectory deserves consideration when a vascular etiology is strongly suspected and a significant stenosis is found

Avoidance of toxins, correction of vitamin deficiencies, discontinuation of causative drugs, initiation of hormonal replacement therapy in cases of deficiency, and treatment of underlying infectious etiologies

• Who are the AD Caregivers? (slide 37)

• Demands of Caregiving (slide 38)

• Technology and Caregiving (slide 39)

• National Support for Caregivers (slide 40)

• How to Contact the ADEAR Center (slide 41)

Improving Support for Families and Other Caregivers

Slide 36

Demands of Caregiving

AD takes a huge physical and emotional toll. Caregivers must deal with changes in a loved one’s personality and provide constant attention for years. Thus, caregivers are especially vulnerable to physical and emotional stress.• Peer support programs can

help link caregivers with trained volunteers. Other support programs can offer services geared to caregivers dealing with different stages of AD.

Support for Caregivers

Slide 38

Treatment of AD…

Tacrine

Cholinesterase inhibitor 1 systematic review with 5 RCTs,

1434 people, 1-39 weeks No difference in overall clinical

improvement Some clinically insignificant

improvement in cognition Significant risk of LFT

abnormalities: NOT USED

Donepezil

Aricept Cholinesterse inhibitor Easy titration (start 5/day, then

10) Side effects: GI (nausea,

diarrhea) Can be associated with

bradycardia… Main effect seems to be

lessening of rate of decline, delayed time to needing nursing home/more intensive care

Other agents…

Rivastigmine Galantamine Cholinesterase inhibitors ?more side effects, more titration

required Future directions:

Prevention of delirium in at risk patients (cholinergic theory of delirium)

Behavioral effects in those with severe dementia?

Treatment of Lewy Body dementia Treatment of mixed Vascular/AD

dementia

Comments about cholinesterase inhibitor studies…

Highly selected patients (mild-moderate dementia)

?QOL improvements… Not known: severe dementia and

mild CI

Memantine

NEJM april 2003 Moderate to severe AD (MMSE 3-

14) N-methyl D aspartate (NMDA)

receptor antagonist; theory that overstimulation of NMDA receptor by glutamate leads to progressive neurodegenerative damage

28 week, double blinded, placebo controlled study; 126 in each group; 67% female, mean age 76, mean MMSE 7.9

Memantine…

Found less decline in ADL scores, less decline in MMSE (-.5 instead of –1.2)

Problem: significant drop outs (overall 28% dropout rate) in both groups; data analyzed did not account for drop outs, followed those “at risk”

Selegiline

Unclear benefit Less than 10mg day, selective

MAO B inhibitor Small studies, not very

conclusive

Vitamin E (alpha tocopherol)

NEJM 1997: selegiline, vit E, both , placebo for tx of AD

Double blind, placebo controlled, RCT with mod AD; 341 patients

Primary outcome: time to death, institutionalization, loss of ADLS, severe dementia

Baseline MMSE higher in placebo group No difference in Primary outcomes;

adjusted for MMSE differences at baseline and found delay in time to NH from 670 days with vit E to 440 days with placebo

Ginkgo Biloba

1 systematic review of 9 double blind RCTs with AD, vascular, or mixed dementia

Heterogeneity, short durations High withdrawal rates; best

studies have shown no sig change in clinician’s global impression scores

Other treatments

NO good evidence to support estrogens or NSAIDS

Other treatments…

Behavioral/agitation: Nonpharmacologic strategies Reasons for NH placement:

Agitation Incontinence Falls Caregiver stress

?Antipsychotics

NO data to support any significant benefit for treating behavioral symptoms of dementia with antipsychotic agents

Small group of patients with active psychoses, disturbing hallucinations, or aggressive behaviors who may have some benefit

Antipsychotics:

Side Effects: Sedation Anticholinergic effects Prolonged QT Edema Orthostasis Weight gain Confusion

Warnings: FDA black box warning for increased

mortality (OR 1.5- 1.7), and increased ?increased stroke risk

Prevention?

HTN and DM linked to future development of ALL types of dementia (not just vascular)…

Large initial studies of treating systolic hypertension in the elderly (SHEPS and others) demonstrated decreased risk of development of cognitive impairment over time in those patients in the original treatment group!

Decreased risk included vascular AND alzheimer type

dementias…

Cholinesterase inhibitors seem to work as well (or as poorly) for both vascular and alzheimer type of dementias…

What is the link? Both common in elderly, may be that one “unmasks” the other…

Conclusion International studies make it clear that dementia

occurs in every country of the world. Dementia affects 1 in 20 people over the age of 65 and 1 in 5 over age of 80

Worldwide there are an estimated 35.6 million people with dementia. By 2050 the number will rise to over 115 million. For at least the last 15 years, the majority of people with dementia worldwide have been living in developing regions of the world. They account already for over 60% of all cases. By 2040 this portion will have risen to 71%.

Conclusion cont’

The worldwide cost of dementia will exceed 1 per cent of global GDP in 2010, at US$604 billion. If dementia care a country, it would be the world’s 18th largest economy

The costs of caring for people with dementia are likely to rise even faster than the prevalence-especially in the developing world, as more formal social care systems emerge, and rising incomes lead to higher opportunity costs.

Conclusion cont’

Dementia is a progressive, degenerative brain syndrome that affects memory, thinking, behavior and emotion

The progressive syndrome of dementia is define as loss of memory plus impairment in at least one other cognitive function, such as aphasia, apraxia, agnosia and disturbance in executive function, which is severe enough to interfere with activities of daily living and represent decline (DSM-IV, 1994

Conclusion cont’

Dementia presents with variety of clinical manifestations regardless of aetiology, and in most cases it caused by organic barain disease. It characterized by three main symptomatic domains as; 1) activities-inability to perform activities of daily life, 2) behaviours-psychiatric symtoms/behavioural disturbances and 3) cognition-neuropsychological impairment

Conclusion cont’

There are four main types of dementia: 1) Alzheimer’s disease (60% of cases), 2) Vascular dementia (30-40%; including about 20% where dual pathology exists), 3) Dementia with Lewy bodies (15% of cases), and 4) Fronto-temporal dementia (5% of cases).

Conclusion cont’

The treatments options for dementia include both pharmacological and nonpharmacological therapeutic approaches. These can be further subdivided into therapies for cognitive impairment and neuropsychiatric disturbances (psychiatric symptoms and behavioural disturbances).

Conclusion cont’

The quality of life patients with dementia is paramount and long-term care of the patient requires continued education and communication with clinicians, primary carers, care staff and family members.

Documents

Rusdi Lamsudin Department of Neurology Faculty of Medicine Indonesian Islamic University Yogyakarta, INDONESIA