Workshop cases

Dr. Jos L Molinuevo

Alzheimers disease and other cognitive disorders unit
ICN, Hospital Clinic I Universitari, Barcelona
BarcelonaBeta Brain Research Centre
Fundaci Pasqual Maragall

Cognition
Cognition (Latin: cognoscere, 'know') can be defined
as the ability to process information from perception,
or previously acquired knowledge (based in
experience)
Cognition is the set of skills and mental processes
related to knowledge: attention, memory, judgment,
reasoning, problem solving, production and
comprehension of language, navigation, etc.

Cognitive exam
History / examination
Overall cognitive state
For cognitive domains:

Attention / processing speed

memory
language
praxias
Visoperceptive and visospatial functions
executive functions
Conduct / character

Global cognitive function

MMSE
30 puntos

Clinical dementia rating

Attention

The state of cognition in which the sensory and mnemonic

information is perceived selectively, allowing the consistent
realization of a planned motor behaviour. This selectivity is
associated with lack of awareness lot of irrelevant stimuli or
memories
Attention requires some level of alert, but the alert is not
always associated with care (the warning precedes attention)
Disturbance in attention:
impaired attention events located in front side of the staff or extrapersonal
space (neglect), unimodal or multimodal
overall inattention: inability to concentrate on a task

Atencin:

valoracin global

Dgitos inversos
Deletrear al revs
Clculo mental
Das de la semana/
meses al revs

Memory

Memory
Alteration in the register of new information: anterograde
amnesia
Alteration in evoking memories already stored (before the
event):
retrograde amnesia (consolidation 1-2 years)
verbal memory
visual Memory
Immediate / working memory
recent memory
Remote / autobiographical memory
Explicit memory (declarative): episodic memory
semantic memory
Implicit memory

Dgitos:
Directos

FREE and CUED selected reminding TEST (FCSRT)

I=Identificacin

Ensayo 1

Ensayo 2

Ensayo 3

Categora

tem

RL1

RF1

RL2

RF2

RL3

RF3

AVE

CUERVO

MAT. LECTURA

ENCICLOPEDIA

VERDURA

APIO

CALZADO

ALPARGATAS

REPTIL

CAIMN

M. CONSTRUCCIN

MRMOL

P.PRECIOSA

TURQUESA

EDIFICIO

PISO

MUEBLE

ESCRITORIO

10

VEHCULO

AUTOCAR

11

HERRAMIENTA

HOZ

12

INST. MUSICAL

ARMNICA

13

UT. COCINA

COLADOR

14

DEPORTE

GIMNASIA

15

PLANTA

JAZMN

16

TIPO BARCO

PESQUERO

Total identificacin (I)

Recuerdo libre (RL)
Recuerdo facilitado (RF)

30 minutos

RL Total
RF Total

Language

Fluencias semnticas y fonmicas (FAS/PMR)

Visoperceptive and visospatial

functions

Test de figuras superpuestas (Poppelreuter):

Respuestas: tenedor, botella, plato, paloma

Test de Percepcin Visual (corte segn media 10/15)

Praxias

Copia Figura
Compleja de Rey

Psicomotor speed

TMT A

Executive Functions :
Set of cognitive skills that allow anticipation and goal
setting, training plans and programs, the initiation of
activities and mental operations, self-regulation of the
tasks and the ability to carry out efficiently
Working memory
abstraction
planning
flexibility
Monitoring and inhibition of behavior

Memoria de trabajo
Dgitos directos

Flexibilidad cognitiva

Test de Stroop - Inhibicin de la respuesta automtica

Abstraccin: Test de semenjanzas

Elemento
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19

Naranja-Pera
Chaqueta-Pantaln
Perro-Len
Calcetines-Zapatos
Tenedor-Cuchara
Mesa-Silla
Barco-Automvil
Piano-Tambor
Ojo-Odo
Aire-Agua
Ordenador-Libro
Poema-Estatua
Mosca-rbol
Huevo-Semilla
Vapor-Niebla
Amigo-Enemigo
Hibernacin-Migracin
Premio-Castigo
Trabajo-Juego

Respuesta

Puntuacin
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
Total

2
2
2
2
2
2
2
2
2
2
2
2
2

Perseveration/ cognitive
flexibility

echolalia
echopraxia
intrusions
"Response-to-next-patient-stimulation sd
Sg applause
Sg release
Sequential movements Luria
Tasks go-no go

Torre de Hanoi - planificacin

Primitives signs from frontal liberation

Palmomentoniano
Prehension reflex
Snout
Flicker
Suction

Behaviour

Case 1: Mrs MB

Case 1 Mr MB
Aged 81, first seen May 2008
2 years history of increasing memory impairment
Medical observation
Time gradient
Constant question repetition
Looses things
Needs list for shopping
Instrumental ADLs preserved, although difficulties at the
subway

Apathy, irritable, moody

Past medical history
Hypertension, on atenolol and amiloride
Mild arthritis, on ibuprofen 400 mg daily
Mild deafness

 Screening testing:
MMSE 22/30
Clock drawing OK
Semantic fluency 13
T@M 24/50 Cutt off score 28/50

MRI

Neuropsychological exam

Blood analysis

Clinical diagnosis:
Alzheimers disease

What therapy would you initiate for

this woman?
a) Donepezil
b) Rivastigmine
c) Galantamine
d) Memantine
e) A cholinesterase inhibitor, plus memantine

Initial medication
Donepezil 5 mg, then 10 mg, daily
initiated
Slight improvement, but MMSE
unchanged
Family noted he was more confident
Improvement in mood
After 18 months MMSE dropped to 19
No additional behavioural or mood
changes

Having progressed over two years, what

therapy will you initiate next?
a) Change to Rivastigmine
b) Change to Galantamine
c) Add memantine
d) a) or b), plus c)
e) None of the above

Difficulty finding the

right word

Initial complain (2001)

Male 61,
For two years has "memory lapses"
consisting of:
He struggles to find the right word
Does not recognize known people
(neighbours, friends, etc)
Small errors in his work with the computer
(forgets recording what was done)
In another centre: MMSE 28; NPS: above
average intellectual level and anomic
difficulties .

Past medical history

Chronic hypertension (home about
50 years)
migraine
Ex-smoker
Industrial engineer
Professor at the School of Industrial
Engineering

No family history of dementia

May 2002
Anxious, hypochondriac attitude
Speaks fluent, no signs of oral apraxia
Prosopagnosia and anomia
No signs of parkinsonism
Complementary studies:
neuropsychological study
cranial CT
cranial MRI

NPS junio02

MMSE 27 (set 26) GDS 3

Test Barcelona abbreviated 88 (cut-off AD 85)
MIS 6/8
Test accentuation of words 28/30
FCSRT: Free 10/48, provided 15 free dif. 6 (lim), fac.dif 8
TMT A 32 "B 64"
Token test 7/7, 4/4, 4/4, 4/4, 4/4, 11/13
Figure Rey: copy 36/36, Instant 13, deferred 9
14/60 Boston Naming test
Stroop A 107; B 70; C 49
Corsi cubes direct Span 3 reverse 4
Summary: Deficits in memory ( fixation and evocation) and
marked difficulty in naming

NPS diciembre02
AVLT 6-7-8-10-10 B5 A6-6; Stagnant
learning curve.
BNT 8/15 Fluency FAS 08.05.11, animals
7
Numerous errors in nomination even
with
high-frequency stimuli. Verbal
fluency is
reduced, especially for
semantic slogan.
TMT A and B (N) He made executive
tasks quickly without interference
alteration .

Febrero03
Septiembre'02: lacunar left corona radiata
that coursed with mild paresis of right
limbs with complete recovery (vascular
etiology - CVRF: AHT)
Occasionally renames food
His wife has the impression that does not
follow/understand meetings or movies"

Octubre05
He has difficulty reading and having a
conversation because he has trouble
understanding things, "has lost the
meaning of the words"
Have a memory problem, but is able to
run errands
Does not recognize people
Computing capacity remains
Very obsessive: strict schedules, things
exact location sudokus compulsively,
very impatient

Junio 06 (7 aos evolucin

aprox)

His wife says he does not understand "anything"

Just use wildcard words (this, that, etc.)
Does not "identify things", ie trying to make orange
juice with potatoes, he ate raw breast chicken or
dog food thinking it was a sausage or ate butter as
if cheese
Nor identifies sounds: for example, the phone rings
and goes to open the door
Down the street does not recognize his children or
his wife or face or by voice, but remember faces in
the Smartbrain

 Make Sudokus, follows the program Know

and win" with some friends makes an
accounting program in Excel (?)
Play dominoes flawless
Use public transportation, not disorienting,
comes to the hospital only from home
Core activities ok.
Compulsive eater and occasional
violations of social norms: in greengrocers
and bakeries gets products and eats
Follow his routine obsessively

TC craneal septiembre06

RM septiembre06

Summary
Presenile onset dementia
Prosopagnosia, anomia, agnosia,
obsessive-compulsive disorder
Constructive praxis, ideomotor,
calculus, space-time orientation,
memory of "everyday" preserved

Diagnosis
Semantic dementia
Criteria for the clinical diagnosis of
dementia Semantics (semantic aphasia with
associative agnosia) (Neary, 1998)
The semantic disorder (difficulty
understanding the meaning of words and /
or identity of objects) is the most prominent
at the beginning and throughout the illness
alteration. Other cognitive functions,
including autobiographical memory, remain
unaffected or relatively preserved.

Memory and Aging Center, UCSF

Gorno-Tempini04
R

Patologa esperable:
DLFT-U + (inclusiones
Neuropathol 2006)
tau -

predominio

neuritas,

Acta

75 years old male referred

for cognitive difficulties 4
years long

Mr. MP
75 years old male
Irrelevant past medical history
Complains of vision difficulties
Not difficulties with seeing details, but
misses the whole picture
Takes his grandchildren and rotates them
to see them properly

Sometimes his hand gets gluedto

objects

Exploracin fsica:
aware of the problem
Reduction of left visual field by
confrontation
Right-left failures recognition
No increase in tone , and tremor

Exploracin neuropsicolgica (I):

MMSE : 24/30
Copy Rey Complex Figure : Altered
Title ( Boston Naming Test ) : 45/60
Understanding orders ( Boston) : 10/15
Selective attention ( Trail Making Test A) :
Alter .
Memory. Curve Memory: 4,5,5,6,7 holds 4
Ideomotor praxis by imitation : 2/5
calculation

Copia Figura
Compleja de Rey

Comprensin rdenes
Ej: Ponga el lpiz al otro
lado del reloj y dele la vuelta a
la libreta

Test de figuras superpuestas (Poppelreuter):

Respuestas: tenedor, botella, plato, paloma

T@M - TEST DE ALTERACIN DE MEMORIA

Rami L, Molinuevo JL, Bosch B, Snchez-Valle R, Villar A.
Unidad Memoria-Alzheimer. Hospital Clnic i Universitari de Barcelona
MEMORIA INMEDIATA "Intente memorizar estas palabras. Es importante que este atento/a"
Repita: cereza (R) hacha (R) elefante (R) piano (R) verde (R)
1. Le he dicho una fruta, cul era? 1
2. Le he dicho una herramienta, cul era? 0
3. Le he dicho un animal, cul? 1
4. Le he dicho un instrumento musical, cul? 0
5. Le he dicho un color, cul? 0
"Despus le pedir que recuerde estas palabras"
"Este atenta/o a estas frases e intente memorizarlas" (mximo 2 intentos de repeticin):
Repita: TREINTA GATOS GRISES SE COMIERON TODOS LOS QUESOS (R)
6. Cuntos gatos haba? 1; 7. De qu color eran? 1; 8. Qu se comieron? 1
(Si 0 decirle la respuesta correcta)
Repita: UN NIO LLAMADO LUIS JUGABA CON SU BICICLETA (R) (mximo 2
intentos):
9. Cmo se llamaba el nio? 1 ; 10. Con qu jugaba? 1
(Si 0 decirle la respuesta correcta)

MEMORIA DE ORIENTACIN TEMPORAL

11. Da semana 1; 12. Mes 1; 13.Da de mes 1; 14.Ao 1; 15.Estacin 1
MEMORIA REMOTA SEMNTICA (2 intentos; si error: repetir de nuevo la pregunta)
16. Cul es su fecha de nacimiento? 1
17. Cmo se llama el profesional que arregla coches? 1
18. Cmo se llamaba el anterior presidente del gobierno? 1
19. Cul es el ltimo da del ao? 1
20. Cuntos das tiene un ao que no sea bisiesto? 1
21. Cuntos gramos hay en un cuarto de kilo? 1
22. Cul es el octavo mes del ao? 1
23. Qu da se celebra la Navidad? 1
24. Si el reloj marca las 11 en punto, en qu nmero se sita la aguja larga? 1
25. Qu estacin del ao empieza en septiembre despus del verano? 1
26. Qu animal bblico enga a Eva con una manzana? 0
27. De qu fruta se obtiene el mosto? 1
28. A partir de qu fruto se obtiene el chocolate? 1
29. Cunto es el triple de 1? 1
30. Cuntas horas hay en dos das? 1

MEMORIA DE EVOCACIN LIBRE

31. De las palabras que dije al principio, cules podra recordar? 2
(esperar la respuesta mnimo 20 segundos)
32. Se acuerda de la frase de los gatos? 2 (un punto por idea: 30 - grises - quesos)
33. Se acuerda de la frase del nio? 1 (un punto por idea: Luis - bicicleta)
MEMORIA DE EVOCACIN CON PISTAS
34. Le dije una fruta, cul era? 1
Se acuerda de la frase de los gatos?
35. Le dije una herramienta, cul? 0
39. Cuntos gatos haba? 0
36. Le dije un animal cul era? 1
40. De qu color eran? 1
37. Un instrumento musical, cul? 1
41. Qu coman? 1
38. Le dije un color, cul? 1 Se acuerda de la frase del nio?
(Puntuar 1 en las ideas evocadas de forma libre) 42. Cmo se llamaba? 1
43. Con qu estaba jugando? 1

Puntuacin: 40/50
Corte para Deterioro cognitivo Leve: 37
Corte para Enfermedad de Alzheimer: 28/50

Test de cancelacin de Albert

- omisin objetos campo derecho

Exploracin neuropsicolgica (II):

Apraxia, agraphia , acalculia

Memory within normality
Impaired visuospatial capacities
Some dysnomia visual confrontation
attentional disorders
In short : Difficulties visuoperceptive - guides
along with attentional disorders and certain
dysnomia and impaired comprehension.
Preservation of global cognitive, intellectual and
memory
Cognitive impairment bilateral parieto -occipital
predominance

TAC craneal

RM craneal

 Over the next two years :

treated with anticholinesterase
Progressive worsening :
Dissociation between reading ( reads ) and total
inability to write.
Unable to recognize right-left
Negligence and failure to use left arm.
Increased tone in the left arm
Low rolling left upper extremity

Normal eye movements

Action and reflex myoclonus

RM (+2 aos)

Right

Right

SPECT cerebral

Oblicuo 0

Oblicuo +1

Oblicuo +2


Hypomimia and hypophonia
Balint syndrome "plus" left
predominance
generalized myoclonus
Normal pain and temperature
sensitivity
Reading, writing and calculation
impossible

El paciente falleci y fue donante del Banco de

tejidos neurolgicos
(UBarcelona-Hospital Clnic)

Hipocampo: DNF-Degeneracin Vacuolar .Placa

IHQ
-A4 amiloideplacas difusas

Crtex cerebral TAU +

(DNF y hebras neur)

Degeneracin neurofibrilar y neurtica y n distrfica

Familial dementia

Clinical History: initial

symptom
2 siblings
79 years old female, consulting
for memory problems lasting 12
months
74 years old male, consulting for
memory problems lasting 18
months

79 years old female

After pelvic fracture developed cognitive
decline
Past medical history:
DM treated with glibenclamide
Depression treated with imipramine and
lormetazepam

Actual problem:

Memory loss
In one occasion, spatial disorientation
Apathy
ADL preserved

Neurological exam
Lower body Parkinsonism
Freezing, short-shuffling steps, wide
based gait
Cognitive:
Oriented in time and space
Optimal attention level
Discrete memory alteration
No language impairment: neither in its
expression nor comprehension

Neuropsychological Results
Memory
Memory Texts (fixation) I (Test Barcelona): 7 N
Delayed Memory Texts : 2 (< 1,5 DE) Altered
CERAD memory List:
learning: 5,4,5 retention: 1 Altered

Visual (Dibujos, CERAD): 3/11 mildly altered

Semantic memory (Animals Fluency): 13 N
Working memory (Dgits, WAIS III):7,5 N

Neuropsychological Results
Language:

Naming (BNT): 48 /60 N

Comprehension of complex orders (BDAE): 15/15
Repetitions: OK
Written: OK

Praxis:
Constructive (CERAD): 11/11N
Imitational praxis: 5/5 N

Neuropsychological Results
Visual perception
Poppelreuter: 10/10 N
VOSP : 21/22 N

Frontal functions
Abstract thinking (similarities): 16 N
Phonetic fluency (FAS): 20 N
Trail Making Test (part A): 85 seconds.

MRI

MRI

74 year old male

18 months history of memory loss
Past medical history:
DM treated with glibenclamide
Depression treated with citalopram and
lormetazepan
Obsessive disorder

Actual problem:
Dense memory loss: extremely repetitive
Forgets family names and the way back home, gets
lost
Apathy, inhibition and irritability
Worsening of previous obsessions

Neurological exam
Lower body Parkinsonism
Freezing, short-shuffling steps, wide
based gait
Cognitive:
Oriented in time and space
Optimal attention level
Marked memory deficit
Naming impaired

Neuropsychological Results

MMSE: 21/30
Memory (CERAD): 2,3,5 retention 0
Naming (Boston):47/60
Order comprehension (Boston):14/15
Trail Making Test A: normal.
Imitation Praxis:5/5
Calculus: normal

MRI

MRI

MRI

Evolution
Both siblings developed a
progressive motor (greater in the
man) and cognitive decline
Died after 7 years
Brain donors
Do they have the same disease?
Is this a genetic disease?

Pathological study
Banc de Teixits Neurolgics
Universitat de Barcelona - Hospital Clnic

Patologa degenerativa tipo Alzheimer: depsitos de amiloide

A-beta
A-beta

Patologa degenerativa tipo Alzheimer: patologa neurofibrilar

ovillo neurofibrilar
degeneracin granulo-vacuolar

cuerpo de Hirano

Tau-AT8

ubicuitina

Diagnsticos

I) AD pathology:
Braak stage V
CERAD Clasification: definite AD
NIA/RI: high probability AD diagnosis
Moderate amyloid angiopathy
II) Atherosclerotic vascular disease

Estudio neuropatolgico
caso 2
Banc de Teixits Neurolgics
Universitat de Barcelona - Hospital Clnic

Balloon neurones (cingulate)

Cortex frontal

Cortex temporal

Cortex

s. blanca

corteza frontal placas astrocticas

AT8

AT8

isoformas tau 3R

isoformas tau 4R

Hippocampus

Argentophilic grain disease

(dentate gyrus)

Hippocampal sclerosis

Diagnsticos neuropatolgicos

I) Primary tauopathy (4R-T): corticobasal

degeneration + argentophilic grain disease
II) Hippocampal sclerosis
III) Limbic TDP43-pathy
IV)Atherosclerotic vascular disease

Thank You