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									Seminario Internacional “Actualización en enfermedad de
Alzheimer y otros trastornos demenciantes”.
Santiago de Chile, 24-25 de noviembre de 2010




Proyecto NEURONORMA:
aportaciones a la evaluación
cognitiva de las demencias
Jordi Peña-Casanova
Secció de Neurologia de la Conducta. Parc de Salut Mar.
Grup de Neurologia de la Conducta. Programa de
Neuropsicofarmacologia
Institut Municipal d’Investigació Mèdica
Barcelona. Espanya




                                           www.neuro-cog.com
1.Proyecto NEURONORMA: la referencia
2.Perfiles clínicos ilustrativos: casos clínicos
3.Perfiles cognitivos de Trastorno Cognitivo
  Leve y Enfermedad de Alzheimer




                                                   4
1.Proyecto NEURONORMA: la referencia
2.Perfiles clínicos ilustrativos: casos clínicos
3.Perfiles cognitivos de Trastorno Cognitivo
  Leve y Enfermedad de Alzheimer




                                                   5
Multicenter Study for Normalization and
Validation of Neurocognitive and Functional
Tools with Genetic and Neuroimaging
Correlation for Detection, Diagnosis and
Follow-up of Cognitive Deterioration and its
Relationship with Quality of Life in Aging and
Dementia (NEURONORMA.ES)

J. Peña-Casanova; R. Blesa; M. Aguilar; B. Gómez-Anson;
R. Oliva; JL Molinuevo; A Robles; MS Barquero;
C Antúnez; C Martínez-Parra; A. Frank-García; M. Fernández

Sponsored by The Pfizer Foundation, Spain
Pfizer’s Medical Department, Spain
Behavioral Neurology Group IMIM, Barcelona
NEURONORMA PROJECT. Part I (normative data)
Archives of Clinical Neuropsychology (2009)




                                              7
Paper 1
Methods & Sample Characteristics




                                   8
NEURONORMA project: Introduction, 1

•   Need of normative data
     –   Lezak et al, 2004; Strauss et al 2006


•   Cognitive test performance is largely influenced by multiple factors
     –   Age
     –   Education
     –   Sex


•   Psychometric properties of neuropsychological tests

•   Cross-cultural isues
     –   Spain. Eg. pretzel versus madalena




                                                                       9
NN Project: Primary Objective

• To collect normative and psychometric information on a
  sample of persons above age 49, living in different Spanish
  Autonomous Communities

   – The normative information was intended on a series of selected
     but commonly used neuropsychological test

   – The final primary objective was to generate a profile
     representation of test performance in order to facilitate
     cross-test comparison and interpretation




                                                                      10
NN Project: Secondary Objectives

1. To generate diagnostic information of the normalized tests
   using discrete-moderate AD as gold standard

2. To describe the scores and the clinical profile of amnesic
   MCI and to generate a diagnostic tool

3. To correlate cognitive abilities with functional abilities
   (ADL), considering data from MCI and AD

4. To correlate clinical cognitive data with functional abilities
   and QoL measures in cases of MCI, and AD.




                                                                    11
NEURONORMA project: Setting

•   Andalusia
     –   Hospital Virgen Macarena. Sevilla. Dr. Carlos Martínez Parra
•   The Basque Country
     –   Hospital de Cruces. Bilbao. Dr. Manuel Fernández
•   Catalonia
     –   Hospital del Mar, IMIN. Barcelona. Dr. Jordi Peña-Casanova
     –   Hospital Clínic. Barcelona. Dr. Rafael Blesa*, Dr. Jose Luis Molinuevo
     –   Hospital Mútua de Terrassa. Terrassa. Dr. Miquel Aguilar
•   Galicia
     –   Hospital Clínico. Santiago de Compostela. Dr. Alfredo Robles**
•   Madrid
     –   Hospital Clínico San Carlos. Madrid. Dra. Marisa Barquero (†)
     –   Hospital Universitario La Paz. Madrid. Dra. Anna Frank
•   Murcia
     –   Hospital Virgen Arixaca. Murcia. Dra. Carmen Antúnez



                                    * Actual: Hospital de la Santa Creu i Sant Pau / **Actual: Hospital   13
NEURONORMA project: Research participants (Controls)

•   Recruitment
    –   (1) Spouses of patients, (2) Senior citizen activity centers, (3) Word of mouth
•   Subjects
    –   Ethnic background: caucasian
    –   Educated in Spanish regardless of the first (native) language [Castilian (Spanish), Catalan,
        Galician or Basque)] in the case of bilinguals
    –   Inclusion Criteria
          a) Informed consent, b) Subjects of both sexes aged over 49y, c) Spanish speaker with at
              least minimal capacity in writing, d) community dwelling with normal IDDD scores, e)
              absence of cognitive impairment (normal MMSE)
    –   Exclusion criteria
          a) History of CNS diseases causing neuropsych. Deficits
          b) Score of 4 or more on the Modified Ischemia Scale (Rosen et al., 1980)
          c) Alcohol or substance abuse
          d) Active or uncontrolled systemic diseases associated with cognitive impairment
          e) History of psychiatric diseases (eg. Major depression, psychosis)
          f) Presence of severe sensorial deficits (loss of vision and/or hearing)


                   Ethical approval                                                                14
                        Granted by the Research Ethics Committee of the IMIM
NEURONORMA project: Research participants (Controls)

•   360 subjects recruited and assessed
•   Four cases excluded
    –   Missing data: 1
    –   Violation of inclusion/exclusion criteria: 3 (minor alcohol abuse, depression, visual problems)




                          Final sample = 356 subjects




                                                                                                     15
Selection & classification tools

•   Mini Mental State Examination (MMSE), (Folstein et al, 1975)
    –   Spanish version: NORMACODEM Project (Blesa et al, 2001)
    –   Controls: Cut-off = 24

•   Interview for Deterioration of Daily Living in Dementia (IDDD),
    (Teunisse et al, 1991)
    –   Spanish version: NORMACODEM Project (Böhm et al, 1998)
    –   Controls: Cut-off = 37

•   Hamilton Depression Rating Scale (HDRS), (Hamilton, 1960)
    –   Spanish version of 17 items

•   Modified Ischemia Score (Rosen et al, 1980)
    –   Cut off = 4

•   Global Dementia Staging (GDS) (Reisberg et al, 1982)
    –   GDS 1 to 5 (6 & 7 excluded); Controls = GDS 1 & 2; MCI = GDS 3; AD = GDS 4 & 5



                                                                                         16
    Classification criteria


                  BCRS, GDS-FAST = Gold Standard
GDS    Concept          Deficits / Capacities
1      Normal adult     No deficit
2      Normal aged      Subjective complaints of memory loss only e.g. forgetting
       adult            where one has placed familiar objects
                        No objective evidence of loss on clinical interview
3      Mild cognitive   Decreased performance in demanding employment and social
       impairment       settings. Objective evidence of impairment only obtained in
                        intensive interview
4      Discrete         Decreased knowledge of current events
       dementia         Decreased ability to perform complex tasks
                        Decreased ability to market, handle finances
5      Moderate         Unable to recall a major aspect of current life
       dementia         Can no longer survive without some assistance


                                                                                17 17
NEURONORMA project: Neuropsychological measures, 1

ATTENTION

•   Verbal Span
     Spanish version: Peña-Casanova (2005)


•   Visuospatial Span (Corsis’s test)
     WAIS-R-NI


•   Letter and Number Sequencing
     WAIS-III, Wechsler (1977)


•   Trail Making Test (TMT)
     Partington & Leiter (1949), Reitan & Wolfson (1993)


•   Symbol Digit Modalities Test (SDMT)
     Smith (1982)



                                                           Paper 2   18
NEURONORMA project: Neuropsychological measures, 2

LANGUAGE

•   Boston Naming Test (BNT), 2nd edition
    Kaplan, Goodglass & Weintraub (2001)


•   Token Test (TT) short form
    De Renzi & Faglioni (1978)




                                            Paper 3   19
NEURONORMA project: Neuropsychological measures, 3

VISUO-SPATIAL ABILITIES

•   Visual Object and Space Perception Battery (VOSP)-Abbreviated
    Warrington & James (1991)


•   Judgment of Line Orientation (JLO) [form H]
    Benton , Hannay & Varney (1975)




                                                        Paper 4     20
NEURONORMA project: Neuropsychological measures, 4

CONSTRUCTIONAL TASKS & MEMORY

•   Rey-Osterrieth Complex Figure (copy and memory) (ROCF)
    Rey (1941), Osterrieth (1944)


•   Free and Cued Selective Reminding Test (FCSRT)
    Buschke (1984) [Buschke, 1973; Buschke & Fuld 1974]




                                                          Paper 5   21
NEURONORMA project: Neuropsychological measures, 5

VERBAL FLUENCY
     Ramier & Hécaen (1970)


Semantic
• Animals, Fruit and vegetables, & Kitchen tools

Formal lexical
• Initial letter “P”, “M”, & “S”

Exluded letter
     Crawford, Wright, & Bate (1995)
•   Excluded “A”, “E”, & “S”




                                                   Paper 6   22
NEURONORMA project: Neuropsychological measures, 6

EXECUTIVE FUNCTIONS

•   Stroop Color-Word Interference Test (SCWT)
    Stroop (1935), Golden (1978)


•   Tower of London-Drexel University version (TOL-Dx)
    Culberston & Zilmer (2001)




                                                         Paper 7   23
Test adaptation

Sequence of forward and backward translations
    –   Erzigkeit et al, (2001), Verhey et al (203, 204)
1. Three forward translations into Spanish
    1. JPC, NGF or Peter Böhm & Celer-Pawlowsky SL, Traducciones, Madid, Spain.
2. The three forward translations were reconciled into one forward
   version
3. The forward version was backward translated into English
4. The original English version was compared with the backward
   translation. Discrepancies were considered.
5. The new version was tested empirically for clarity and
   acceptability (cognitive debriefing). Al formulations found to be
   problematic were dicussed and necessary changes worked out.




                                                                                  24
Procedures

•   Raters: Psychologists and neuropsychologists
•   Training
     – Two meetings
     – Videotapes, Cards with instructions
•   Case Record Forms
     – Optic Character Recognition (OCR) (Teleform ®, Elite by Cardiff Software)
•   Two-step study
     – First Step (Day 1): (a) informed consent, sociodemographic data,
       family antecedents, health habits, anthropometric data, medical
       antecedents…; (b) clinical interview; (c) screening tools; (d) diagnosis &
       inclusion/exclusion criteria.
     – Second Step (Days 2 & 3): Neuropsychological battery




                                                                               25
Data Management and Statistical Analysis, 1

•   European Biometrics Institute (EBI). Barcelona, Spain

•   SPSS 13.0 & SAS 8.2 for Windows

•   Controls re-categorized into two groups (cut-off >65 years)
    –   Theoretical differentiation of “normal adult” (GDS 1) versus “normal-aged adult”
        (GDS 2)

•   Basic descriptive analyses
    –   Count, percent of total, M, SD, CI 95%, & range
    –   Comparison of age groups
         • Continous variables: Student’s t-test
         • Nominal & ordinal variables: χ2 test & Fishers’s exact test when needed

•   Uniform normative procedure
    –   CO-NORMING (Ivnik et al, 1992; Lucas et al, 2005)




                                                                                       26
Data Management and Statistical Analysis, 2
Uniform normative procedure

a. Maximization of the number of participants
    –   Overlapping interval strategy (Pauker, 1988)
    –   Midpoint age intervals
    –   Age range around each mid-point was 10 years

b. Definition of age, education and sex effects
    –   Coefficients of correlation (r) and determination (Shared variance) (r2) of raw scores with
        age, years of education and sex were determined (Lucas et al, 2005)

c. Creation of age-adjusted normative tables
    –   The frequency distribution of the raw scores was converted into age-adjusted scaled scores:
        NSSA (Neuronorma Scaled Score-age adjusted) (Ivnik et al., 1992): M = 10; SD = 3


d. Education adjustments
    –   Years of education modellation: NSSA = k + (β * Educ)
    –   Age & Education adjusted Scaled Scores (NSSA&E): standard linear regression

                         NSSA&E = NSSA – (β * [Educ-12]) (Mungas et al, 1996)


                                                                                                      27
Estratificación tradicional de edades




  50                 60 61                    70 71                   80




 • Rangos amplios de edad
    • Problemas en la comparación entre el sujeto y el rendimiento del grupo


                                                                           28
Mid-point (Pauker, 1988) & overlapping intervals


           57-58-59

  53                         63


                      60-61-62

           56                            66


                                  63-64-65

                      59                      69
                                                   29
NEURONORMA Scaled Scores




  NEURONORMA
  Scaled Score




                     Mayo Clinic (MOANS, MOAANS) = NEURONORMA
                                                        30
Percentile   Scaled
 Ranges      Scores
   <1          2
    1          3
    2          4        Scaled score = label
   3-5         5         assigned to every
  6-10         6          percentile range
  11-18        7
  19-28        8      E. g. a raw score between
  29-40        9       percentiles 6 & 10 has a
  41-59       10           scaled score of 6
  60-71       11
  72-81       12
  82-89       13
  90-94       14
  95-97       15
   98         16
   99         17
   >99        18
Transformation of raw scores to NSSA & NSSA&E

• Example
   – Patient AAA: age: 70 years old; 15 years of education
   – Boston Naming Test raw score (RS): 41

• Two step procedure
   – Table 1: Age-adjusted NEURONORMA scores (NSSA)
      • Select the appropriate column corresponding to the patient’s age
      • Find the patient’s RS and subsequently refer to the corresponding
        NSSA and percentile rank

   – Table 2: Age- and education-adjusted NEURONORMA scores (NSSA&E)
      • Select the appropriate column corresponding to the patient’s years
        of education
      • Find the patient’s NSSA and subsequently refer to the corresponding
        NSSA&E



                                                                            32
Table1. Boston Naming Test. Age-adjusted Scaled Score
Patient AAA: age: 70 years old
BNT raw score (RS): 41                                  NSSA = 7




                                                              33
Table1. Boston Naming Test. Age-adjusted Scaled Score
Patient AAA: age: XX
BNT raw score (RS): 41




                                                        34
Table2. Boston Naming Test. Age- & education-adjusted Scaled Score
Patient AAA: 15 years of education
BNT NSSA = 7                                           NSSA&E = 6




                                                                35
Neuronorma Record Form




                         36
         Neuronorma Record Form



                                Scaled score 6
                               Percentiles 10 - 6
                               z = -1.26 / -1.59




                             Scaled score 5
                            Percentiles 5 - 3
                            z = -1.60 / -1.95




                          Scaled score 4
                           Percentile 2
                         z = -1.96 / 2.19




                                                    37
El VOSP NO cumple el supuesto de normalidad
Neuronorma Record Form


                  Scaled score 6
                 Percentiles 10 - 6
                 z = -1.26 / -1.59

               Scaled score 5
              Percentiles 5 - 3
              z = -1.60 / -1.95




                                      38
    Neuronorma Record Form


Verbal Attention & immediate memory. Backward: Mental tracking, working memory

Visual-spatial attention & immediate memory. Backward: Mental tracking, working memory

Visuomotor traking, divided attention, mental flexibility, motor function
Divided attention, visual scanning & tracking. Perceptual & motor speed
Visual perception & gnosis, lexicon (naming)
Verbal comprehension, working memory
Visuo-spatial relationships (visual orientation)
Visual perception. Visual-spatial constructional ability. Planning. Visuomotor speed

Verbal learning
Retrieval
Verbal memory

Visual memory. Visual-spatial constructional ability. Planning. Visuomotor speed

Verbal productivity, semantic memory, language, executive function


Cognitive flexibility, selective attention, cognitive inhibition, speed



Problem-solving, executive planning, response inhibition, visuospatial & working memory



Object perception & recognition
                                                                                       39
Space perception
1.Proyecto NEURONORMA: la referencia
2.Perfiles clínicos ilustrativos: casos clínicos
3.Perfiles cognitivos de Trastorno Cognitivo
  Leve y Enfermedad de Alzheimer




                                                   40
Caso clínico: JRO (H 1046977)

• Sexo: mujer
• Edad: 79 años
• Dominancia manual: derecha
• L1: catalán, L2: castellano (bilingüe balanceado)
• Escolaridad: estudios superiores, licenciada en filología (20
  años)
• Profesión: profesora de literatura. Jubilada

• Consulta en enero de 2009 por problemas de memoria desde
  el año 2007. No alteraciones significativas en la vida diaria.

• Exploración neurológica: normal
JRO
H 1046977
Feb 2009




            42
JRO
H 1046977
Feb 2009




Memorias
Diferidas
normales




            43
Ref # 1


   Envejecimiento (psicométricamente) normal
                    (GDS 2)



                     Caso JRO
                   (H 1046977)
Caso clínico: AAS (H. 257980)

•   Sexo: Mujer
•   Edad: 55 años
•   Dominancia manual: derecha
•   L1: Catalán; L2: castellano
•   Escolaridad: básica (7 años)

•   Consulta (2-2009) por problemas de memoria iniciados 2007.
     – Olvido de citas, de acontecimientos recientes, fechas relevantes, recetas
       de cocina habituales. Pérdida de objetos y desorganización en general.
     – Necesidad de explicaciones complementarias para comprender
       situacones o indicaciones
     – Ansiedad con cierta desinhibición
•   Exploración neurológica normal
AAS.
H 257980




           46
AAS. H 257980




                47
AAS
H 257980
Abril 2009




             48
AAS
H 257980
Abril 2009




             49
Ref # 3


          Demencia: Alzheimer presenil




                    Caso AAS
                   (H. 257980)
Caso clínico: AGF (H. 427264)

•   Sexo: Mujer
•   Edad: 49
•   Dominancia manual: derecha
•   L1: Catalán, L2: Castellano
•   Escolaridad: 12 años
•   Profesión: administrativa

•   Fumadora, Enolismo importante (…/…).
•   Tres años de evolución: Cambios de carácter. Pérdida de memoria
AGF (H. 427264)




                  52
AGF
H 427264
Mayo 2009




            53
AGF
H 427264
Mayo 2009




            54
Ref # 4


    Enolismo crónico: Amnesia tipo Korsakov




                    Caso AGF
                   (H. 427264)
Ref # 6


    Epilepsia temporal: lesión temporal mesial
        derecha. Exéresis temporal derecha



                     Caso MGB
                    (H 116639)
Caso clínico: MGB (H 116639)

•   Sexo: Hombre
•   Edad: 43
•   Dominancia manual: Derecha
•   L1: castellano
•   Escolaridad: 13 años

•   Epilepsia del lóbulo temporal farmacorresistente
•   RM 3T: lesión infiltrativa en porción medial del lóbulo temporal
    derecho (parenquimatosa)

• Intervención: Exéresis de amígdala, cuerpo y parte de cola del
  hipocampo derecho
• Anatomía patológica: desorganización cortical y gliosis
Caso MGB
(H 116639)




             60
Ref # 7


     Epilepsia temporal. Cavernoma temporal
      izquierdo. Exéresis temporal izquierda.
           Estudio pre y postquirúrgico


                 Caso JRM (H 876560)
Caso clínico: JRM (H. 116639)

•   Sexo: Hombre
•   Edad: 45
•   Dominancia manual: Derecha
•   L1: castellano
•   Escolaridad: 14 años



•   Estudio prequirúrgico. Epilepsia temporal mesial

•   Angioma cavernoso temporal izquierdo (lesión nodular de 5 mm de
    diámetro en la porción anterior y medial del lóbulo temporal izdo.)
JRM
H 876560




           64
Ref # 8


  Status epiléptico no convulsivo: necrosis laminar
                     hipocámpica



                      Caso MPM
                      (H 407247)
Caso clínico: MPM (H 407247)

•   Sexo: Hombre
•   Edad: 53
•   Dominancia manual: Derecha
•   L1: castellano
•   Escolaridad: 10 años

•   Epilepsia (1) parcial compleja con sensación epigástrica y posterior
    pérdida de conocimiento (2) Secundariamente generalizadas tras 1
•   Urgencia 09-05-2010: 24 horas de evolución: alteración del nivel
    de conciencia, desorientación y trastorno la conducta

•   RM: Hiperintensidad T2/FLAIR del hipocampo izquierdo con signos
    de necrosis laminar en secuencias T1, evolución de un status
    epilepticus
MPM
H 407247




           69
MPM
H 407247
Mayo 2010




            70
MPM
H 407247
Julio-2010




             71
MPM
H 407247
Mayo 2010
Julio 2010




             72
1.Proyecto NEURONORMA: la referencia
2.Perfiles clínicos ilustrativos: casos clínicos
3.Perfiles cognitivos de Trastorno Cognitivo
  Leve y Enfermedad de Alzheimer




                                                   82
MCI & AD sample

• Controls
   – n = 356 (NEURONORMA refference group)
• MCI
   – n total = 79
   – Petersen et al criteria
• AD
   – n total = 100
   – NINCDS-ADRDA criteria




                                             83
Statistics

• NSSA&E (Neuronorma Scaled Score, Age & Education
  adjusted)

• Descriptive statistics
– N; Mean; SD; 95% CI for mean; Median (percentile 50)

• Comparisons
– ANOVA: p-value. Bonferroni




                                                         84
MCI vs Healthy Controls

Significant differences on all test

Except on
• Digit span forward
• Digit span backward
• Tower of London: total initiation time




                                           85
Neuronorma Record Form




                         • MCI




                             86
Neuronorma Record Form




                    MCI = Healthy Controls
                               • MCI




                                      87
MCI vs AD

Significant differences on all test

Except on
• VOSP number localization
• Judgment of line orientation
• Tower of London correct score (total of items)
• Tower of London initiation time
• Rey-Orterrieth Complex Figure. Copy: Time




                                                   88
Neuronorma Record Form




                         • AD




                                89
Neuronorma Record Form




                         • MCI
                         • AD




                             90
Judgment of Line Orientation: NSSA&E

N          Mean     SD      Lower         Upper       Median
                             95%          95%
Cont 341   11.05   2.75     10.75         11.34             11
MCI 72     8.98    2.88        8.30        9.66         9.5
AD 63      7.82    3.63        6.91        8.74             8


                          p-value ANOVA: <.0001
                          Multiple comparisons
                          p-value (Bonferroni correction)
                                      Control MCI      AD
                          Control     -      <.0001    <.0001
                          MCI                --        ns
                          AD                           --

                                                                 91
Boston Naming Test: NSSA&E

N          Mean    SD        Lower       Upper        Median
                              95%        95%
Cont 341   10.25   2.49      9.99        10.52          10
MCI 72     8.06    2.91      7.39         8.73              8
AD 63      5.41    2.66      4.87         5.95              5


                          p-value ANOVA: <.0001
                          Multiple comparisons
                          p-value (Bonferroni correction)
                                     Control MCI       AD
                          Control    -       <.0001    <.0001
                          MCI                --        <.0001
                          AD                           --

                                                                92
FCSRT Total recall: NSSA&E

N          Mean     SD         Lower         Upper       Median
                                95%          95%
Cont 346   10.04    2.88          9.7        10.35             10
MCI 75     5.79     3.22          5.04        6.54             5
AD 96      3.05     1.45          2.71        3.38             3


                             p-value ANOVA: <.0001
                             Multiple comparisons
                             p-value (Bonferroni correction)
                                         Control MCI      AD
                             Control     -      <.0001    <.0001

                             MCI                --        <.0001
                             AD                           --
                                                                    93
Animal fluency: NSSA&E

N          Mean     SD     Lower         Upper        Median
                            95%          95%
Cont 346   10.07   2.59        9.8       10.35          10
MCI 75     8.08    2.89        7.4        8.74              8
AD 96      5.52    2.66        4.9        6.06              5

                          p-value ANOVA: <.0001
                          Multiple comparisons
                          p-value (Bonferroni correction)
                                     Control MCI       AD
                          Control    -       <.0001    <.0001

                          MCI                --        <.0001
                          AD                           --

                                                                94
Neuronorma Record Form




                         • MCI




                             95
Neuronorma Record Form




                         • MCI
                         • AD




                             96
Neuronorma Record Form




                                   • MCI
                                   • AD
               AD Critical Tests




                                       97
AD Critical Tests beyond memory (FCSRT)

Attention / execution
• TMT
• SDMT
Language
• Naming: BNT
• Comprehension: Token Test
Execution: lexical-semantic
• Verbal fluency: animals
Attention / Speed
• Stroop – color
Execution (planning, reasoning)
                                           Barcelona Test
• Tower of London – Total execution time   Time orientation
• Tower of London – Total solving time


                                                       98
MIS & FCSRT

NEUROIMAGING

               114
Hippocampal segmentation: manual vs. automated




                                                 115
                                Controls (n = 34)
                                MCI (n = 24)
                                Alzheimer D (n = 20)

Journal of Geriatric Psychiatry and Neurology, 2009
MRI based volumetric data in cc3 of global brain
tissue & ROIs
Effect size (Cohen’s d) values for memory outcomes
and significant MRI measures




                                  FCSRT: Controls vs. Alzheimer
Conclusiones

               119
Conclusiones, 1

• La conormalización de instrumentos permite establecer
  disociaciones cognitivas de forma objetiva y fiable (grupo de
  referencia único y método estadístico único)

• Los perfiles cognitivos NEURONORMA tienen interés en la
  diferenciación de cuadros cínicos y en el establecimiento de
  correlaciones clínico-topográficas (ilustrado por casos
  clínicos)




                                                             120
Conclusiones, 2

• Se ha definido el perfil cognitivo de Controles, MCI y
  Alzheimer mediante auna batería conormalizada.

• Los individuos con MCI presentan un perfil paralelo a los
  sujetos con EA
   – Se observan diferencias significativas prácticamente todas las
     variables
   – Aunque existen diferencias significativas, a excepción de la
     memoria, todas las puntuaciones de los sujetos con MCI caen
     dentro de la normalidad estadística

• Un serie de variables diferencian los sujetos con MCI de los
  sujetos con EA: Variables críticas mas allá de la memoria

                                                                      121
Conclusiones, 3

• El FCSRT constituye el test de más interés en el diagnóstico
  de los trastornos de memoria en la enfermedad Alzheimer
   – Se propone como test de diagnóstico precoz
• El poder de diferenciación de los test es superior al de la RM
  volumétrica (primero se altera la función y luego la
  estructura)

• El FCSRT presenta una excelente correlación con datos de
  neuroimagen: volumen hipocampico
   – La versión breve del FCSRT, el MIS, presenta correlaciones
      similares con los datos de neuroimagen
   – Los datos están en favor del uso del MIS como instrumento de
      cribado

                                                                    122
Parc de Recerca Biomèdica Barcelona
jpcasanova@parcdesalutmar.cat




                                 Barcelona
                                                  124
                  Institut Municipal d’Investigació Mèdica

								
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