Adéla Mitášová
Světlana Skutilová
University Hospital Brno
De (without) - Mens (sense)
 silent epidemic of the 21. century
 illness of the whole family – objectiv anamnesis!
 about 150.000 patients in the Czech Republic
(10 million inhabitants…)
COGNITIVE DISTURBANCE
 (memory,orientation,speech, attention,
delusions, hallucination)
 BEHAVIOUR DISTURBANCE
(personality, emotion-
apathy,aggression,depression)
 LOSS OF SELF-SUFFICIENCY
(employment…..take care of himselfs)
A. PRIMARY DEGENERATIVE DEMENTIA
B.VASCULAR DEMENTIA
C. SECONDARY DEMENTIA
 Neurologist + psychiatrist + geriatrist
 cooperation with neuropsychologist
TARGET:
examine all lobes of the brain
 The most exact tests are for F lobe
 The less exact tests are for T lobe
 The least exact test are for O+P lobe
 Standardization (comparison of each other)
 Sensitivity (minimal deficit detection)
 Repeatable (monitoring over time)
 Quantification (score)
 Examination takes a few hours
 Bed - side tests
Short, assessment of cognitive functions ever
by general practitioner or ambulantory
specialist
The type of dominant lobe impairment helps us with
differential diagnostics of dementia type
F (behavior function) FTD
T+P (memory function) AD
P+O (visualconstructive function) DLBD
multiple impairment VD
 The most used test since 1975
WHY??
ADVANTAGES:
 quick
 easy administration
 requirement of Czech insurance company
 monitoration of dementia progression
DISADVANTAGES:
Not enough sufficient for
 early stage of dementia (MMSE often normal)
 diagnosis of FTD (no examination of F lobe)
 diagnosis of DLBD (no examination of
O + P lobe)
 Mild 25 - 18 p.
 Moderate 17 – 6 p.
 Severe 5 – 0 p.
 Standard score 28-30 p.
 IMPORTANCE – therapeutic strategy !
 SCORE
Maximum 100 points (MMSE is a part of ACE)
 Less than 82 points
: sensitivity of dementia 84%
: specificity of dementia 100%
MMSE
 10-15 min
 monitoration of already developed dementia
ACE
 25 -30 min
 early dementia
 FTD, DLBD
ACE:
 Suspicion of the dementia
 Expected another kind of dementia than AD
orVD
MMSE:
 Already developed dementia
 Monitoration of dementia
 The causes of dementia: about 60 various diseases
A/ PRIMARY NEURODEGENERATIVE Dementia
B/VASCULAR Dementia
C/ SECONDARY Dementia
attending basic NEUROLOGICAL or INTERNAL diagnosis
(disturbance of metabolism, nutrition, endocrinopathy, toxic brain
disturbance)
 Primary target: Exclude SECONDARY Dementia
(TREATABLE)
 EVERY!! NEUROIMAGING (CT,MRI,PET MRI)
 BloodTests : blood count, renal/liver biochemistry,
vitamine B12, thyroid function tests, Cu +
ceruloplasmin, serology HIV + syphilis
 CSF (basic, triplet, protein 14-3-3)
 (EEG)
 (genetics)
 1. Mild cognitive impairment (MCI)
- 10-15% transformation to AD
 2. DEPRESSION (pseudodementia)
- therapeutic test with antidepressants
 3. DELIRIUM
- sudden onset, fluctuation, duration days,
quantitative consciousness failure
 4. Side effects of FARMACOTREATMENT in
old age
- anticholinergics (biperiden, tricyclic
antidepressants)
- opioids
- hypnotics
HISTOLOGICAL CRITERIA:
1. AMYLOIDOPATHIES - AD
Amyloid plaques… deposits of beta amyloid
2.TAUOPATHIES - FTD, CBD, PSP
Pick bodies …. deposits ofTau protein /ubiquitin protein/
3. SYNUKLEINOPATHIES - DLBD, PDD
Lewy bodies … deposits of alfa synuklein
MOST OFTEN!!
 60% of all the kinds of dementia
 Preclinical stage even 15 years
 Neuropsychological examination:The first sign DISTURBANCE
OF RECENT MEMORY
T-P lobe
 HISTOLOGY: AMYLOIDOPATHIES
AGE !!!! 65 years - 5%
85 years - 50%
 Low education
 Low intelect and mental activity
 Low physical activity
 Social isolation
 Female gender (3,1 x)
 Genetic factors (early onset)
 1. AD with early onset (up to 60 years age)
5%
genetic risk faktors … APO E4
(alela E4 for apolipoprotein E )
 2. AD with late onset (most of the patients) !
sporadic form
 1. PROBABLY
Disturbance of 2 or more cognitive functions,
progression between 60-90 years, depression,
anxiety, delusions, hallucinations, emotion instability,
incontinency.
Possible neurologic signs (epilepsy, parkinsonism)
 2. DEFINITIVE
Histological verification by brain biopsy (post mortem)
 (BRAIN CT):
- atrophy ofT lobe (P), extension of lateral
ventricles
 BRAIN MRI:
- hippocampal atrophy (high specifity)
 BRAIN PET MRI
i.v. aplication of radioactive isotopes
FDG (fluorodeoxyglucose) - decreased glukose
metabolism in MEDIOTemporal LOBE,
gyrus cinguli, precuneum … late T-P lobe
In University Hospital Brno since 2017
 AMYLOID BRAIN PET MRI :
In vivo detection of amyloid plaques
Expensive /1800 dollars/
ADVANTAGE: MCI….initiation of treatment
early diagnostics
negative result exclude AD
clinical trials
NO: asymptomatic patient with family history
In University Hospital Brno since february 2023
 NORMAL PATOLOGY
 TRIPLET: 3 biomarkers, proteins
BETA-AMYLOID decreased
TAU-PROTEIN increased
P/TAU-PROTEIN increased - most exact
 Negativ result exclude AD
 In University Hospital Brno since 2019
 AS SOON AS POSSIBLE
 SYMPTOMATIC : NO CURE, NO STOP, BUT SLOW
DOWN
A/ ACETYLCHOLINESTERASE INHIBITORS
I: Mild and moderate stage of AD (MMSE 25-13)
 Donepezil
 Rivastigmin
 Galantamin
Side effects: impaired digestion, parkinsonism
B/ MEMANTIN – influence on NMDA receptors
I: Moderate stage of AD (MMSE 17-6)
A+B/ DUALTHERAPY (MMSE 17-13)
Mild stage ... Memory Late stage … Behaviour
 TREATMENT of DEPRESSION + ANXIETY:
SSRI, SNRI, BZD
Cave tricyclic antidepressants - anticholinergical
side effect
 TREATMENT of PSYCHOTIC SYMPTOMS:
antipsychotics
 DO NOT prescribe: nootropics, vasodilatans
 Parallel therapy !!: cognitive training
physical training
(only to swallow a pill is insufficient)
 We have got yet no new drug since 2004
 New trials: biologic therapy - monoclonal antibodies against amyloid
 HISTOLOGY: SYNUKLEINOPATHIES
20% of dementia, underdiagnosed
HISTOPATHOLOGY: Lewy bodies (brain stem, limbic
cortex, neocortexT-F)
DAT scan - asym. hypofunction in striatum
PET MRI – sym. cortical hypoperfusionT-P-O
Neuropsychological examination: visual-constructive
dysfunction T-P-O
 CLINICAL signs: fluctuating cognitive deficit
visual hallucinations
parkinsonism
 TREATMENT:
CAVE neuroleptic hypersensitivity (quick deterioration
of parkinsonism)
- Only nontypical antipsychotics
- Acetylcholinesterase inhibitors
- L-Dopa in early stage
 HISTOLOGY: TAUOPATHIES (ubiquitinopathies)
 Neuropsychological examination : 1. SYMPTOM
BEHAVIOUR OR LANGUAGUE DISTURBANCE
F +T lobe
 EARLY onset (45 - 65 years)
 FAMILIAR OCCURENCE (30-50%)
 RAPID PROGRESSION
 1. BEHAVIOURAL (Frontal) - 55%
 2. LANGUAGE (PPA)
 Combination of both
DOMINANT symptoms:
 Early change of behaviour (perseverative,
stereotypes)
 Early change of personality
 Early emotional changes (apathy, verbal or
physical impulsivity)
LATE somatic signs :
 Parkinsonism, MND (10-15 % )
NEUROIMAGING (MRI, PET MRI):
- sym. atrophy of F + frontT lobe
TREATMENT:
 Deficiency of serotonin. and dopamin.
transmiter system - SSRI
 Nontypical antipsychotics
 (cognitivs rather no – minimal effect)
 Subtypes: non - fluent aphasia
semantic
logopenic
 DOMINANT sign: APHASIA
 NEUROIMAGING: asym. atrophy ofT lobe
(dominant)
 TREATMENT: Speech therapy
 2o% of dementia
 after stroke 5x higher risk of onset
 men more disabled than women
 diagnostics is problematic, differentiation of
AD often only histologically, ussual is mixed
dementia ( AD +VD)
 Brain MRI (CT)
 Neuropsychological examination:
more than 1 lobe is impaired
 SONO of cerebral arteries
 CSF: biomarkers negativ
1. D. due to mikroangiopathy (90% because of HT)
Binswanger´s disease (subcortical leukoencefalopathy)
2. D. due to strategically lokalized ischemia (F,T)
3. Multiinfarct D. (multiply small and large infarcts)
4. D. due to difusse hypoxic-ischemic encefalopathy
(5.) D. familial : AMYLOID angiopathy (frequent stroke)
CADASIL (AD, mutation of chromosome 19)
- young age, migraine, skin biopsy

 Primary and secondary PREVENTION of
cerebrovascular diseases
 Acetylcholinesterase inhibitors
 Memantin
 DO NOT Prescribe: nootropics, vasodilatant
drugs
 Very common!
 Dominant AD + vascular changes
 DominantVD + alzheimer changes
 Symptom of basic NEUROLOGICAL DG
 Symptom of basic INTERNAL DG
Symptom of BASIC NEUROLOGICAL DG:
 Normotense hydrocephalus
 Brain tumors
 Kraniocerebral injury - chronic SDHematoma
 Epilepsy
 Neuroinfection - JCD, neurosyphilis, AIDS
 Sclerosis multiplex - late stage
 Huntington´s disease
 Wilson´s disease
Symptom of basic INTERNAL DG:
 Hepatal encephalopathy
 Renal (uremic) encephalopathy
 Endocrinopathy (hypothyreodism)
 Deficiency B12,B1,B6,folat acid
 Alcohol abuse
 Prion disease
 Incidence 1-2 per million
 100% mortality
 Incubation period more than 10 years
 The most infectious tissue: BRAIN!
- cerebral dura, cornea, blood?
RISK:
 Transplant from affected person
(from 2007 mandatory testing cornea donor)
 Neurosurgical operation (contaminated instruments)
 Disinfection, UV radiation – DO NOT DESTROY
 Rapidly progressive dementia
 Cerebellar or visual signs (ataxia)
 Extrapyramidal signs (myoclonus)
 Pyramidal signs
 Akinetic mutism
 AUTOPSY MANDATORY
 EEG: periodic sharp wave complexes
 CSF: 14-3-3 protein detection
 Brain MRI: high signal abnormalities in
caudate nucleus + putamen
 INCURABLE
 1. SPORADIC 85%
50-70 years
Duration 6 months
 2. GENETIC (mutation) 10-15%
 3. NEW variant (infectious) 2-3%
19-39 years
Duration 1-1,5 years
Due to consumption of infectious animal (BSP)
 KURU ( kanibalism, Papua N. Guinea)
 FFI Fatal familiar insomnia
 Gerstman-Straussler-Scheiner d.
Thank you for your attention