DEMENTIA Prof . Dr.

Ioana Miclutia
Definition
 Progressive impairment of various cognitive
functions, occurring in alertness after the age of 18
 Global impairment of intellect, that impairs
 Primary
 memory and
 thinking

 Secondary
 functionality and
 personality
Dementia
 Marked by progressive declines in
memory
visual-spatial functions
performance of routine tasks
 language and communication skills
abstract thinking
ability to learn and carry out
mathematical calculations.
History
 dementatus (Latin)-out of one’s mind
 dementia-Celsus 1rst cent ad
 Oribasius –physician of emperor Julian-supposed a
cerebral atrophy
 Esquirol-senile dementia
 Griesinger-1845 disease of cerebral arteries
 Alzheimer-1907,1911 hystopathological changes
and described aphasia, apraxia, agnosia
Alois Alzheimer
SO… What is Dementia?
 It is NOT part of normal aging! It is a disease!

 It is more than just forgetfulness - which is part

of normal aging

 It makes independent life impossible

 Aging Changes in Cognition…
 Normal aging changes = more forgetful & slower to learn

 MCI – Mild Cognitive Impairment = 1 problem area

 Immediate recall, word finding & complex problem solving problems
(½ of these folks will develop dementia in 5 yrs)

 Dementia = Chronic thinking problems in > 2 areas

 Delirium =Rapid changes in thinking & alertness
(seek medical help immediately )
 Depression = cognitive impairment is reversible
chronic unless treated, poor quality , I “don’t know”, “I
just can’t” responses, no pleasure
can look like agitation & confusion
 DEMENTIA

Lewy Body
Dementia Other Dementias
•Metabolic
Vascular
Alzheimer’s (Multi-
•Drugs/toxic
•White matter disease
Disease infarct) Fronto-
•Mass effects
Dementia Temporal •Depression
•Early onset Lobe •Infections
Dementias •Parkinson’s
•Normal onset
Increase in numbers of people with dementia, by
development status

ADI World Alzheimer Report 2009, Eds Prince & Jackson

 Incidence rates

7,7 million of new diagnosis/year

Africa
7%
Europe
North America
30% 11%

Latin America
5%

Asia
47%

WHO Report 2012 – Dementia a Public Health Priority

Prevalence AD

Age

Evans.JAMA.1989;262:2551-2556
 Dementia – types

fronto- temporal dementia – 5 % others – 5 %

Lewy body d – 15 %

Vascular dementia – 20 % Alzheimer’s dementia – 50 %

Most frequent types of dementia

Demen??
vascular?
15-25% Demen??
mixt?
10-20%

Demen?? Demen??
degenerativ? degenerativ?
senil? presenil?
Alzheimer Alzheimer
45-60% 10-15%
Dementia
 Two Types:
 Reversible

 Irreversible

 Individuals must have intensive medical physical

to rule out reversible types of dementia.
Dementia
 Reversible:
 D= Drugs, Delirium
 E= Emotions (such as depression) and
Endocrine Disorders
 M= Metabolic Disturbances
 E= Eye and Ear Impairments
 N= Nutritional Disorders
 T= Tumors, Toxicity, Trauma to Head
 I= Infectious Disorders
 A= Alcohol, Arteriosclerosis
 Other causes
Substrate disease

Degenerative Parkinson’s , Huntington, Pick dementia

Traumatic Head trauma, subdural hematoma

Infectious Encephalitis, Creutzfeldt-Jakob, HIV

Intoxications Alcohol, drugs, CO, heavy metals,

solvents
CSL Hydrocephaly

Tumoral Brain Tumors, metastasis

Metabolic Hypoglycemia, liver and renal

insufficiency,
Endocrine Hypotiroidism
 Diagnosing AD
Definite AD - Histopathological evidence (requires autopsy)
- Course and examination characteristic of AD

Probable AD - Deficits in > 2 areas of cognition

- Onset 40-90 (usually > 65); progressive course
- Other causes excluded

Possible AD - Deficit in only 1 area of cognition

- Atypical course
- Other dementia causes present

Unlikely AD - Sudden onset

- Focal signs
- Seizures or gait disturbance early in course
 Costs

World Alzheimer report 2010

Causes of AD

 genetic (cromosomes19, 21, 14, 1 and probable

12)
 vascular (cerebro-vascular amiloidosis)
 toxic (aluminium)
 traumatic
 inflammatory (acute phase reactions)
 infectious (slow virus, herpes)
 Oxidative stress
 estrogen
 Biochemical mechanism
synthesis

acetilcolinesterase choline

Acetylcholine

acetiltransferaze acetate
degradation

The inhibition of acetilcholinesteraze facilites the availability of acetylcholine

 Acetyl
CoA Astrocyte
Presynaptic
Neuron + Choline
Choline
NR
ChAT BuChE

Noncholinergic
Action ACh
MR
BuChE
ACh Choline
+
Synaptic AChE
Postsynaptic Acetate
Neuron Cleft

AChE
MR NR MR NR

Cholinergic Receptors
Normal AD

AP NFT
Normal Brain Cells

Neurotransmitters (AChE)– being

sent – message being communicated
to the next cell
Normal Brain Cells

Once the message is sent, then

enzymes lock onto the messenger
chemicals and take them out of
circulation so a new message can be
sent
Brain Cells with Alzheimer’s

Less
neurotransmitter
Further to go to get to the
plaques next cell
tangles

Enzymes (AChE inhibitors) –

get to them BEFORE they
deliver their message
What do Alzheimer’s drugs DO?

Alzheimer’s drugs provide

FAKE messenger chemicals
that distract the enzymes.
They attach to the Fake
AChE & the message can get
thru

Donezepilum (Aricept), Rivastigminum (Exelon), Galantaminum

(Reminyl)
Histopathology

 amyloidal plaques

 Neurofibriles
The generation of amyloidal plaques
Neuroimage of AD

 RMN

 PET
THE RISK FACTORS
 negative:  protective:
- increased age
- Female - men
- HTA, hyperlipidemia ,obesity - Active living style
- cardiac disease
- diabetes - High education
- family history of AD
- Smoking
- head trauma - Special cognitive
- trisomy 21 training (actor..)
- limited education
- Routine jobs
Mandatory Explorations
 Neuropsychological testing – screening for cognitive
changes
 A thorough physical & medical history
 Blood work
 A neurological exam
 A good history from the person and the family of the
‘problem’
 A complete medication review

 A CAT scan or MRI (atypical Alzheimer’s – PET scan)

 FOLLOW-UP and counseling or at least a referral

Supplementary tests

 The clock test

DIAGNOSIS
 Dementia of the Alzheimer type
- DSM IV : presence of memory impairment and the
associated presence of at least one other symptom of
cognitive decline
- aphasia,
- apraxia,
- agnosia or
- abnormal executive functioning);
- also a continuing and gradual decline in functioning,
impairment in social or occupational functioning and the
exclusion of other causes of dementia
- age of onset early (at age 65 or below- type II) or late
(after age 65- type I)
Evolution and progression of AD

30
Score Mini-Mental State Examination

30
Cognitive symptoms
25
25
Loss of functional
20
20 independence

15
15 Behavioral problems

10
10
Nursing home placement
55

00
11 22 33 44 55 66 77 88 99
Years
Progression of Alzheimer’s disease
Comparative nosologies
ICD-10


 AD
 DSM-V-Neurocognitive


Precocius
tardive
Disorders (DSM-IV
 Vascular dementia Dementia, Delirium and
 Acute onset
 Multinfarct amestic and other
Subcortical

 mixt cognitive disorders)
Dementia NS
 Delirium

 Pick
 Creutzfeld-Jakob
 Huntington  Major NCD
 Parkinson
 HIV  AD, VD, PD, LB, HD,
Delirium
Amestic disorder HIV....
MCI
 Mild NCD
Precocious signs and symptoms
 Difficulties of acquisition of new information
 Forgetfulness in recent stored data and
 Conservation of old memories and fair good retrieval
of repeated data
 Difficulties in precise naming
 Less involvement in social, professional tasks
 The memory deficit is hided by isolation, hesitation,
excuses
 Lavishness
 Domestic accidents
Clinical signs
 Progressive memory loss (recent towards old)
 Difficulties in learning and understanding new
information and retrieval of long term memories
 Missing appointments
 Misplacing objects
 Topographical disorientation-get lost and difficulties
in unfamiliar places
 Confabulation
AD clinical features
 Language- impoverished speech, aphasia, mutism
 Problem solving difficulties- executive function
 Impaired judgment
 Diminished capacity to perform complex motor tasks
(driving, cooking)
 Failure to accurately recognize objects by their qualities
(agnosia)
 Personality changes
 Low impulse control (voracity, hyper sexuality)
 Sleep disorders and diurnal naps
 Behavioral disorders (agitation, delusions, jealousy,
hallucinations)
 AD dg criteria

Diminished
Short term memory
+
ALTERATION
APHASIA OR APRAXIA OR AGNOZIA or ABSTRACT TH.
JUGMENT

Social, vocational and professional decline

End stages
 Mutism
 Indifferency/violent outbursts
 Lying passive in the bed
 Somatic complications
 Incontinence
 Respiratory difficulties
 Severe dementia with need for total assistance in ADLs
(dressing, bathing, continence), unable to walk, only able to
speak a few words
 Co morbid conditions – aspiration pneumonia, urosepsis,
decubiti, sepsis
 *Unable to maintain caloric intake with weight loss of 10%
or more in 6 months (and no feeding tubes)
 Psychometric Tools

}
 Clinician’s Interview-based
Impression of Change ( CIBIC ) global assessment
 Clinical Dementia Rating (CDR )

Alzheimer’s Disease Assessment

}

Scale – cognitive subscale
Severity of cognitive deficit
 Mini – mental state examination (
MMSE )

 Progressive Deterioration Scale

( PDS )
} Severity of functional decline
and QOL
Delirium vs. Dementia
 Delirium defined- characterized by a disturbance of
consciousness and a change in cognition that develop over
a short period of time
 Agitation, illusions, inversation of wake-sleep
 Fluctuating course
 About 10-15% of surgical patients experience delirium,
and 15-25% of medicine inpatients will experience
delirium
 30% Surgical Intensive Care Unit patients develop
delirium, and up to 30% of AIDS patients while inpatient,
will develop delirium
Treatment
 Objectives
 To postpone the cognitive deterioration
 To assess the co-morbidities

 To counteract mood and behavioral disturbances

 To organize a familiar and safe surrounding

 Cognitive jogging

 Assist emotional family and nursing staff

 Special care facilities

Brain Cells with Alzheimer’s

Less
neurotransmitter
Further to go to get to the
plaques next cell
tangles

Enzymes (AChE inhibitors) –

get to them BEFORE they
deliver their message
How you help…

 Sight or Visual cues

 Verbal or Auditory cues

 Touch or Tactile cues

Medication
 Acetylcholinesteraze inhibitors
 Donepezil5-10 mg Tablets
 Rivastigmine 6-12 mg Dispersable
 Galantamine 16-24 mg Solution
patches
 Glutamatergic modulators
 Memantine 10-20 mg
 Vascular and nootrophic enhancers
 Estrogen replacement
 Mood stabilizers, AD, antipsychotics, sleep hygiene
PHARMACOTHERAPY
 ANTIOXIDANTS
 SELEGILINE (selective MAO-B inhibitor): 5-10
mg/day is used in mild to moderate DAT
 α TOCOPHEROL 1,000 IU twice daily may slow
the progression of moderate DAT
 both may delay a poor outcome in dementia but no
current evidence demonstrates benefits from
combining them
PHARMACOTHERAPY
 ADDITIONAL MEDICATIONS:
- psycho stimulants (metylphenidate 2.5-5 mg/day)
- nonsteroidal anti-inflammatory drugs (indometacin)
- antiplatelet agents (hydergine)
- hormones (estrogen, medroxyprogesterone)
- highly active antiretroviral therapy
TREATMENT
 particular attentions must be provided to caretakers
and family members who deal with frustration,
grief and psychological burnout as they care for the
patient over a long period of time
 Proper assessment of HTA, hyperlipidemia,
obesity, cardiac disease, diabetes, smoking
ENVIROMENTAL AND BEHAVIOR
MANAGEMENT
 the home should be organized to allow for
simplicity of routines: prominent display of
calendars, schedules and photographs and names of
people close to the patient
 events that trigger problematic behaviors should be
identified and minimized
 vehicle keys, power tools and sharp household
should be secured
ENVIROMENTAL AND BEHAVIOR
MANAGEMENT
 institutional placement: painful decision for patient,
family and physician
 loss of home environment leads to further
confusion, behavioral regression and increased risk
for depression
 the lack of or loss of a primary caregiver may
predict early institutionalization
ENVIROMENTAL AND BEHAVIOR
MANAGEMENT
 examples of behaviors that cannot be safely be
managed at home:
 assaultive or threatening behavior, continuing to
drive despite prohibitions, inability to maintain
feeding, drinking, dressing and toileting functions
ENVIROMENTAL AND BEHAVIOR
MANAGEMENT
 Admission to a psychiatry inpatient unit skilled in
dealing with dementia patients may be needed for
severely regressed, suicidal, violent or psychotic
patients especially if complex
psychopharmacological regimen is considered