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Anticipating the future: The diagnosis of Alzheimer's disease in the predementia and prodromal phases

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Marcelo L Berthier at University of Malaga
Marcelo L Berthier
Guadalupe Dávila at University of Malaga
Guadalupe Dávila
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EDITORIAL
449
El acceso limitado a unidades de me-
moria y demencia es en parte respon-
sable de que la mayoría de los afecta-
dos por la enfermedad de Alzheimer
(EA) sea remitido para diagnóstico y
tratamiento cuando se encuentra en
fases leves y moderadas de la demen-
cia [1]. A pesar de la reconocida efica-
cia de los tratamientos disponibles en
ambas fases de la demencia [2,3], la
evidencia indica que ya es demasiado
tarde para prevenir, revertir y contro-
lar la inexorable progresión del dete-
rioro cognitivo, conductual y funcio-
nal. En consecuencia, es razonable su-
gerir que la anticipación del diagnósti-
co de la EA a fases precoces será de
crucial importancia en los años veni-
deros, en los que dispondremos de
agentes farmacológicos modificado-
res de la naturaleza de la enfermedad.
En este número de la revista, Valls-Pe-
dret et al [4] dan un importante paso
adelante en esta dirección revisando
las estrategias disponibles para esta-
blecer el diagnóstico de la EA en las
fases presintomática y prodrómica (fase
sintomática predemencia de la EA).
El grupo de Molinuevo [4] revisa
críticamente los criterios actuales del
deterioro cognitivo leve (DCL) y la EA.
Aunque la contribución principal del
constructo sindrómico DCL en las dos
décadas pasadas ha sido concienciar a
los clínicos acerca de la necesidad de
diagnosticar la EA en fases tempranas,
los autores señalan apropiadamente
que es imperativo abandonar el con-
cepto de DCL, pues un porcentaje con-
siderable de los pacientes que satisfa-
cen los criterios diagnósticos actuales
de DCL no tienen EA. De hecho, más
del 30% de pacientes evaluados for-
malmente en unidades de neurología
conductual por quejas subjetivas de
fallo cognitivo no mostraron déficits
neurológicos y las quejas cognitivas se
atribuyeron finalmente a trastornos
psiquiátricos no relacionados con la
EA [5]. Además, una encuesta reciente
que evaluó la opinión de 420 miem-
bros (tasa de respuesta: 48%) de la
American Academy of Neurology (AAN)
acerca del constructo DCL y de las es-
trategias de tratamiento adoptadas
reveló que un número no desdeñable
de neurólogos encontró limitaciones
de este constructo [6]. Los miembros
de la AAN encuestados señalaron al-
gunos de los beneficios de establecer
el diagnóstico de DCL, tales como favo-
recer la planificación del futuro (87%),
motivar la disminución de actividades
de riesgo (85%), ayudar a la planifica-
ción de las finanzas (72%) y prescribir
medicamentos (65%). Sin embargo,
algunos miembros encontraron des-
ventajas, como dificultad en diagnos-
ticar el DCL (23%) y causar preocupa-
ción excesiva (20%), particularmente
en aquellos casos que pueden ser fal-
sos positivos, por lo que abogan por
redefinir el DCL como ‘EA temprana’
(21%) [6]. Por último, la inclusión de
casos de DCL en ensayos clínicos que
después no desarrollaron EA podría
explicar la ausencia de eficacia de al-
gunos fármacos [7]. El grado de insa-
tisfacción con la aplicación sistemática
del constructo clínico DCL es consisten-
te con la posición que defienden Valls-
Pedret et al [4]. Los criterios que se
han aplicado hasta ahora para el diag-
nóstico de EA (NINDS-ADRA, DSM-IV)
también se han tornado obsoletos,
pues requieren la presencia de de-
mencia para el diagnóstico y, como es
bien sabido en esta etapa, las altera-
ciones patológicas son irreversibles y los
mecanismos compensatorios (p. ej.,
plasticidad neuronal), limitados.
Se impone, pues, aplicar los nue-
vos criterios diagnósticos para la EA
[8]. La presencia de un déficit de me-
moria episódica más un resultado anor-
mal en algún marcador biológico como
la resonancia magnética, líquido cefa-
lorraquídeo o tomografía por emisión
de positrones, o la presencia de una
mutación autosómica de EA son crite-
rios necesarios para el diagnóstico
[4,8]. La inclusión de los marcadores
biológicos en el diagnóstico es un
avance importante en la identificación
temprana (presintomática y prodró-
mica) de la EA, y sin duda redundará
en optimizar la selección de partici-
pantes incluidos en ensayos clínicos
con nuevos agentes modificadores de
la naturaleza de la enfermedad [9].
Sin embargo, los nuevos criterios tie-
nen el defecto de excluir a un tercio
de pacientes que inician la EA de for-
ma atípica (sin afectación de la me-
Anticipando el futuro: diagnóstico de la enfermedad
de Alzheimer en las fases predemencia y prodrómica
Marcelo L. Berthier, Guadalupe Dávila
Unidad de Neurología Cognitiva y
Afasia; Centro de Investigaciones
Médico-Sanitarias (CIMES);
Universidad de Málaga (M.L. Berthier,
G. Dávila). Área de Psicobiología;
Facultad de Psicología; Universidad
de Málaga (G. Dávila). Málaga,
España.
Correspondencia:
Dr. Marcelo L. Berthier. Unidad
de Neurología Cognitiva y Afasia.
Centro de Investigaciones
Médico-Sanitarias (CIMES).
Universidad de Málaga. Campus de
Teatinos. Marques de Beccaria, 3.
E-29010 Málaga.
E-mail:
mbt@uma.es
Cómo citar este artículo:
Berthier ML, Dávila G. Anticipando
el futuro: diagnóstico de la
enfermedad de Alzheimer en las
fases predemencia y prodrómica.
Rev Neurol 2010; 51: 449-50.
© 2010 Revista de Neurología
Véase:
Valls-Pedret C, Molinuevo JL,
Rami L. Diagnóstico precoz de
la enfermedad de Alzheimer:
fase prodrómica y preclínica.
Rev Neurol 2010; 51: 471-80.
www.neurologia.com Rev Neurol 2010; 51 (8): 449-450
M.L. Berthier, et al
www.neurologia.com Rev Neurol 2010; 51 (8): 449-450450
moria) [10]. La evidencia indica que la
EA es una condición heterogénea en
su expresión clínica y neuropatológi-
ca, y esta variabilidad en la localiza-
ción de los cambios histopatológicos
explica que no todos los pacientes ini-
cien el deterioro cognitivo con afecta-
ción de la memoria episódica [10]. La
utilización de diferentes marcadores
(neuroimagen, genotipado de APOE,
neuropsicología, análisis del líquido
cefalorraquídeo) puede ayudar a iden-
tificar la EA en estos casos de inicio
atípico [11].
En conclusión, el artículo de Valls-
Pedret et al [4] es importante y opor-
tuno porque promueve el acercamien-
to a las fases más precoces de la EA y
emplea evaluaciones (líquido cefalo-
rraquídeo, genética, neuropsicología,
neuroimagen) basadas en la eviden-
cia científica actual de individuos asin-
tomáticos con riesgo genético (muta-
ciones) o ambiental (factores de ries-
go vascular, mala reserva cognitiva) o
de aquéllos con síntomas incipientes
de EA sin demencia (EA prodrómica).
El camino por recorrer requiere aunar
esfuerzos para franquear la barrera
translacional (translational roadblock)
[12] existente entre la investigación
básica/clínica y la práctica diaria, y
promover que los avances emergen-
tes en el diagnóstico temprano de la
EA sean cada vez más accesibles en el
ámbito clínico.
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Article
  • Nov 2009
We assessed the cognitive and functional outcomes of donepezil treatment in mild versus moderate Alzheimer's disease (AD) patients. We performed a 6-month prospective, observational, multicenter study of the progression of cognitive and functionality abilities in a large sample patients with AD who initiated treatment with donepezil in monotherapy. According to baseline mini mental state examination (MMSE), patients were divided in two groups: mild AD (MMSE ≥ 21) and moderate AD (MMSE <21). Patients were evaluated with the memory alteration test (M@T) and the Alzheimer's disease functional assessment and change scale (ADFACS) at baseline and at 6 months. A total of 403 patients finished the study (mild AD=152; moderate AD=251). The MMSE total score and M@T score remained stable at 6 months in the whole sample, with MMSE memory domain and M@T free and cued recall domains improving significantly from baseline. Total ADFACS, instrumental (IADL) and basic activities of daily living (BADL) got significantly worse, with the worsening being significantly greater in the moderate AD group. Significant differences between the groups favoring mild AD were observed for MMSE memory, orientation and language domains, M@T temporal orientation and semantic memory domains, and for IADL. We concluded that in AD patients on donepezil, cognition remains stable at 6 months. The beneficial effect of donepezil treatment, in terms of cognition and functionality, is greater for mild than for moderate AD.
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