Cognitive dysfunction in Parkinson's disease related to the R1441G mutation in LRRK2.

OBJECTIVE: The neuropsychological characteristics of patients with Parkinson's Disease (PD) associated with R1441G mutation in the LRRK2 gene (R1441G-PD) are not well known. The aim of this study was to examine the cognitive status and mood of R1441G-PD patients. METHODS: Thirty patients with R1441G-PD were compared with thirty idiopathic PD (i-PD) patients who were matched by age, sex, education, disease onset age and duration, using a comprehensive battery of neuropsychological test, and considering the Movement Disorder Society (MDS) criteria for the diagnosis of Mild Cognitive Impairment (PD-MCI) and dementia (PD-Dementia). RESULTS: The mean scores in the depression and anxiety scales were similar in the two groups. Depressive symptoms were detected in 31.8% of R1441G-PD and 25% of i-PD patients and anxiety symptoms were evident in 4.5% and 15%, respectively, but the differences were not significant. The only neuropsychological test on which there was a significantly worse performance in the R1441G-PD group was the Boston naming test but the difference became not significant when Bonferroni's correction was applied. The prevalence of PD-MCI was 30% in both R1441G-PD and i-PD, with no differences in the number and type of domains altered given that executive function, memory and attention were mainly affected. PD-Dementia was diagnosed in 13.3% (n = 4) of R1441G-PD and 26.7% (n = 8) of i-PD patients (difference was not significant). CONCLUSION: In conclusion, significant differences were not detected between R1441G-PD and i-PD in cognitive, depression and anxiety scales, or PD-MCI and PD-Dementia prevalence, and the cognitive profile was identical in the two groups.

Prevalence and European comparison of dementia in a ≥75-year-old composite population in Spain.

OBJECTIVES: To estimate dementia prevalence in Spain. MATERIALS AND METHODS: Nine probabilistic and geographically defined samples participated. A screening design based on the MMSE was implemented. Positively screened individuals underwent clinical evaluation. The total number of cases in Spain was estimated. Prevalence was confronted to that of other European countries. RESULTS: Five hundred and forty-six persons aged ≥75 participated, 49 had dementia (35 with Alzheimer's disease [AD], 10 with vascular dementia [VD], 4 other; 25 first diagnosed in the study). Age- and sex-adjusted prevalence and estimated nationwide cases were 7.5% (95% CI 5.4-9.7), 5.6 (95% CI 3.7-7.5) and 1.4 (95% CI 0.5-2.3), and 290,000 (95% CI 208,000-372,000), 214,000 (95% CI 141,000-288,000) and 54,000 (95% CI 20,000-88,000) for dementia, AD and VD, respectively. CONCLUSIONS: Dementia prevalence in Spain is comparable to other European populations, while a high number of undiagnosed cases live in the community. The potential impact of Mediterranean diet, hypertension control and decreasing vascular risk factors is discussed.

"Frontotemporoparietal" dementia: clinical phenotype associated with the c.709-1G>A PGRN mutation.

BACKGROUND: Mutations in the progranulin gene (PGRN) are a major cause of frontotemporal lobar degeneration with tau-negative and ubiquitin-positive neuronal inclusions. Most previous studies aimed at characterizing the clinical and neuropsychological phenotype of PGRN mutation carriers included patients with different PGRN mutations, assuming that the common proposed pathogenetic mechanism of haploinsufficiency will lead to a comparable phenotype. METHODS: We studied 21 patients with a single pathogenic splicing mutation in the PGRN gene (c.709-1G>A) in the same tertiary referral center using homogenous diagnostic criteria and protocols. All patients were of Basque descent. RESULTS: Patients exhibited a variable phenotype both in age at onset and initial symptoms. Behavioral variant frontotemporal dementia (52.4%) and progressive nonfluent aphasia (23.8%) were the most common presenting syndromes. Apathy was the most common behavioral symptom. Patients developed a relatively rapidly progressive dementia with features that led to a secondary diagnosis in 61.9% of cases 2 years after primary diagnosis. Notably, this secondary or tertiary diagnosis was corticobasal syndrome in 47.6% of cases, which confirmed the neuropsychological features of parietal lobe dysfunction seen at the initial assessment in 81.8% of patients. CONCLUSIONS: Patients carrying the c.709-1G>A mutation in the PGRN gene showed heterogeneous clinical and neuropsychological features and commonly developed corticobasal syndrome as the disease progressed.

[Tremor: update and controversy]. / El temblor: actualidad y controversias.

INTRODUCTION: Tremor is the most common movement disorder. The differential diagnosis on its origin is sometimes difficult and the number of conditions that include this symptom as part of their clinical spectrum continues to increase. AIMS: To provide an update on aspects that may help in the process of diagnosis, to review the main lines of therapy and to reflect on tremor within the context of Parkinson's disease. DEVELOPMENT: Complementary techniques in the study of Parkinson's disease, such as DaT-SCAN or the study of the cardiac sympathetic pathway by means of cardiac scintigraphy with meta-iodobenzylguanidine (MIBG), have helped in the aetiological diagnosis of this symptom; nevertheless, the patient's clinical history continues to be the main source of information for an accurate diagnosis. Pharmacologically, the therapeutic approach has varied very little and the outcomes of surgical procedures are still described as an alternative in medication-resistant cases. In Parkinson's disease, tremor at rest is a characteristic clinical sign that comprises a series of peculiarities, and the interrelation between essential tremor and this disease is always a controversial issue. The appearance of cases that have been diagnosed as Parkinson's disease, but in which the nigrostriatal pathway remains intact, opens up the spectrum even wider. CONCLUSIONS: In this paper we review the data available today that help in the differential diagnosis of tremor; the particularities concerning Parkinson's disease from the diagnostic, therapeutic and genotypic point of view are also discussed.

El temblor: actualidad y controversias / Tremor update and controversy

esumen. Introducción. El temblor es el más común de los trastornos del movimiento. El diagnóstico diferencial sobre su origen resulta en ocasiones difícil, y cada vez son más las entidades que describen este síntoma dentro de su espectro clínico. Objetivos. Actualizar los aspectos que pueden ayudar en el proceso diagnóstico, revisar las principales vías de tratamiento y reflexionar sobre el temblor en el contexto de la enfermedad de Parkinson. Desarrollo. Las técnicas complementarias en el estudio de la enfermedad de Parkinson como el DaT-SCAN, o el estudio de la vía simpática cardíaca mediante la gammagrafía cardíaca con metayodobencilguanidina (MIBG), han ayudado en el diagnóstico etiológico de este síntoma; no obstante, la anamnesis sigue siendo la principal fuente de información para un diagnóstico preciso. En el abordaje terapéutico no han existido apenas variaciones a nivel farmacológico, y se siguen describiendo los resultados de procedimientos quirúrgicos como alternativa en los casos resistentes a la medicación. En la enfermedad de Parkinson, el temblor de reposo como signo clínico característico encierra en sí una serie de peculiaridades, y la interrelación del temblor esencial con esta enfermedad es siempre un motivo de controversia. La entrada en escena de los casos diagnosticados de enfermedad de Parkinson, pero con integridad en la vía nigroestriada, abre aún más el espectro. Conclusiones. En este artículo revisamos los datos actuales que ayudan en el diagnóstico diferencial del temblor, haciendo mención a particularidades relacionadas con la enfermedad de Parkinson desde el punto de vista del diagnóstico, del tratamiento y del genotipo (AU)

Summary. Introduction. Tremor is the most common movement disorder. The differential diagnosis on its origin is sometimes difficult and the number of conditions that include this symptom as part of their clinical spectrum continues to increase. Aims. To provide an update on aspects that may help in the process of diagnosis, to review the main lines of therapy and to reflect on tremor within the context of Parkinson’s disease. Development. Complementary techniques in the study of Parkinson’s disease, such as DaT-SCAN or the study of the cardiac sympathetic pathway by means of cardiac scintigraphy with meta-iodobenzylguanidine (MIBG), have helped in the aetiological diagnosis of this symptom; nevertheless, the patient’s clinical history continues to be the main source of information for an accurate diagnosis. Pharmacologically, the therapeutic approach has varied very little and the outcomes of surgical procedures are still described as an alternative in medication-resistant cases. In Parkinson’s disease, tremor at rest is a characteristic clinical sign that comprises a series of peculiarities, and the interrelation between essential tremor and this disease is always a controversial issue. The appearance of cases that have been diagnosed as Parkinson’s disease, but in which the nigrostriatal pathway remains intact, opens up the spectrum even wider. Conclusions. In this paper we review the data available today that help in the differential diagnosis of tremor; the particularities concerning Parkinson’s disease from the diagnostic, therapeutic and genotypic point of view are also discussed (AU)

Prevalencia de factores de riesgo vascular en poblaciones españolas de 70 años y más en estudios puerta a puerta de enfermedades neurológicas / Prevalence of vascular risk factors among Spanish populations aged 70 years and over, as reported in door-to-door studies on neurological diseases

Introducción. El objetivo de este trabajo es reanalizar estudios puerta a puerta sobre enfermedades neurológicas de los ancianos donde se estudiaron factores de riesgo vascular (FRV), describiendo sus características metodológicas y las prevalencias de los mismos. Métodos. Se identificaron las encuestas en dos fases, dirigidas a la obtención de prevalencias de ictus, demencias y parkinsonismos que obtuvieron en el cribado datos individuales de al menos tres de los FRV siguientes: hipertensión arterial (HTA), tabaquismo, diabetes mellitus e hipercolesterolemia. Se elaboró un cuestionario para la recogida de datos de cada estudio y se construyó una base de datos compartidos. Se cuantificaron y analizaron las prevalencias de FRV mediante regresión logística. Resultados. En total la población reanalizada, residente en siete áreas geográficas en 1994-2002, ascendió a 12.510 personas de 70 años y más. La información disponible en FRV era fundamentalmente autorreferida. La prevalencia de HTA autorreferida fue 25,7% en hombres y 44,2% en mujeres y la de HTA medida, 61 % y 71,9 %, respectivamente. Las poblaciones con tensión arterial (TA) obtenida mediante medición directa presentaban riesgos mayores (OR: 1,74; IC 95%: 1,51-2,01, y OR: 1,48; IC 95%: 1,33-1,64). Las prevalencias de diabetes, hipercolesterolemia y tabaquismo declaradas fueron 14,3, 23,3 y 8,5 %, respectivamente. Conclusiones. La prevalencia de FRV en ancianos españoles es alta, aunque la calidad de los datos es insuficiente para el estudio de su relación con la demencia, parkinsonismos y enfermedad cerebrovascular. Las diferencias entre la TA medida y la autorreferida sugieren la existencia de HTA no detectada y un amplio margen para la prevención

Introduction. The aim of this study was to re-analyze door-to-door studies on neurological diseases among the elderly, in which vascular risk factors (VRF) were studied, describing methodological characteristics and prevalence of VRF. Methods. The surveys were identified in two phases. They were aimed at ascertaining prevalence of stroke, dementias or Parkinsonisms and, at the time of individual screening, had collected data on at least three of the following VRF: arterial hypertension (AHT), smoking habit, diabetes mellitus and hypercholesterolemia. A questionnaire was drawn up to collect the data reported in each study, and a database was constructed. VRF prevalences were quantified and analyzed using logistic regression. Results. The total of the re-analyzed population was 12,510 persons aged 70 years and over, residents in seven geographic areas during the period 1994-2002. Information available on VRF was essentially self-reported. The prevalence of self-reported AHT was 25.7 % in men and 44.2 % in women, and that of measured AHT was 61 % and 71.9 %, respectively. Populations with arterial pressure obtained by direct measurement registered 138 higher risks (OR: 1.74; 95 % CI: 1.51-2.01, and OR: 1.48; 95% CI: 1.33-1.64). Reported prevalence of diabetes, hypercholesterolemia and smoking habit were 14.3 %, 23.3% and 8.5 %, respectively. Conclusions. There was a high prevalence of VRF among the Spanish elderly population. However, its relationship with dementia, Parkinsonisms and cerebrovascular disease could not be studied due to the poor quality of the VRF data. The differences between measured and self-reported arterial pressure suggest the existence of undetected AHT and wide scope for prevention

[Prevalence of vascular risk factors among Spanish populations aged 70 years and over, as reported in door-to-door studies on neurological diseases]. / Prevalencia de factores de riesgo vascular en poblaciones españolas de 70 años y más en estudios puerta a puerta de enfermedades neurológicas.

INTRODUCTION: The aim of this study was to re-analyze door-to-door studies on neurological diseases among the elderly, in which vascular risk factors (VRF) were studied, describing methodological characteristics and prevalence of VRF. METHODS: The surveys were identified in two phases. They were aimed at ascertaining prevalence of stroke, dementias or Parkinsonisms and, at the time of individual screening, had collected data on at least three of the following VRF: arterial hypertension (AHT), smoking habit, diabetes mellitus and hypercholesterolemia. A questionnaire was drawn up to collect the data reported in each study, and a database was constructed. VRF prevalences were quantified and analyzed using logistic regression. RESULTS: The total of the re-analyzed population was 12,510 persons aged 70 years and over, residents in seven geographic areas during the period 1994-2002. Information available on VRF was essentially self-reported. The prevalence of self-reported AHT was 25.7 % in men and 44.2 % in women, and that of measured AHT was 61 % and 71.9 %, respectively. Populations with arterial pressure obtained by direct measurement registered 138 higher risks (OR: 1.74; 95 % CI: 1.51-2.01, and OR: 1.48; 95% CI: 1.33-1.64). Reported prevalence of diabetes, hypercholesterolemia and smoking habit were 14.3 %, 23.3% and 8.5 %, respectively. CONCLUSIONS: There was a high prevalence of VRF among the Spanish elderly population. However, its relationship with dementia, Parkinsonisms and cerebrovascular disease could not be studied due to the poor quality of the VRF data. The differences between measured and self-reported arterial pressure suggest the existence of undetected AHT and wide scope for prevention.

[A pilot study on a specific measure for sleep disorders in Parkinson's disease: SCOPA-Sleep]. / Estudio piloto sobre una medida especifica para los trastornos del sueno de la enfermedad de Parkinson: SCOPA-sueño.

INTRODUCTION: There is a high prevalence of sleep disorders in Parkinson's disease (PD). AIMS. To assess some basic metric attributes of the SCOPA-Sleep scale, a measure for PD patients; secondary objective: to check the impact caused by the sleep disorder on the health-related quality of life (HRQoL) of patients and their caregivers. SUBJECTS AND METHODS: 68 PD patients and their main caregivers; measures: Hoehn and Yahr staging, SCOPA-Motor, Clinical Impression of Severity Index (CISI-PD), PDSS, Hospital Anxiety and Depression Scale, SCOPA-Psychosocial, and EuroQoL. Carers filled in a PDSS questionnaire about patient sleep and HRQoL measures (SF-36, EuroQoL). SCOPA-Sleep acceptability, scaling assumptions, internal consistency, construct validity and precision were determined. RESULTS: SCOPA-Sleep acceptability and scaling assumptions resulted satisfactory, although the nocturnal sleep subescale (SC-Ns) showed a mild ceiling effect (22.1%) and a defective convergent validity was found for daytime sleepiness (SC-Ds) item 6. Internal consistency also was satisfactory for both scales (alpha = 0.84 and 0.75, respectively). The correlation between SC-Ns and PDSS was high (rs = -0.70), as it was between SC-Ns and PDSS questionnaire by caregiver (rs = -0.53). The corresponding coefficients with the SC-Ds gained lower values (rs = -0.41 y -0.50). Standard error of measurement was 1.45 for the SC-Ns and 1.76 for the SC-Ds. Both, patient and caregiver HRQoL showed a loose association with the sleep measures. CONCLUSION: SCOPA-Sleep is a feasible, consistent, and useful scale for assessment of sleep disorder in PD patients. A weak association between sleep disorder and HRQoL was found.

Estudio piloto sobre una medida específica para los trastornos del sueño de la enfermedad de Parkinson: SCOPA-sueño / A pilot study on a specific measure for sleep disorders in parkinson's disease: scopa-sleep

Introducción. En la enfermedad de Parkinson (EP) existe una alta prevalencia de trastornos del sueño. Objetivos. Comprobar los atributos métricos básicos de la escala SCOPA-sueño para pacientes con EP; objetivo secundario: analizar el impacto del trastorno del sueño en la calidad de vida relacionada con la salud(CVRS) del paciente y de su cuidador principal. Sujetos y métodos. 68 pacientes con EP y sus cuidadores principales. Se aplicaron: Hoehn y Yahr, SCOPA-motor, impresión clínica de gravedad (CISIPD),escala PDSS, Hospital Anxiety and Depression Scale, SCOPA-psicosocial y EuroQoL. El cuidador cumplimentó un cuestionario PDSS sobre el sueño del paciente y las medidas de la CVRS(SF-36, EuroQoL). Se analizaron la aceptabilidad, las asunciones escalares, la consistencia interna, la validez de constructo y la precisión de la SCOPA-sueño. Resultados. La SCOPA-sueño mostró aceptabilidad satisfactoria y asunciones escalares. La subescala sueño nocturno (SC-Sn) presentó leve efecto techo (22,1%), y la subescala somnolencia diurna (SC-Sd), defectuosa validez convergente del ítem 6; la consistencia interna de ambas resultó satisfactoria(alfa = 0,84 y 0,75, respectivamente). SC-Sn correlacionó significativamente con la PDSS (rS= –0,70) y con el cuestionario PDSS cumplimentado por el cuidador (rS= –0,53), y fueron menores los valores respectivos para la SC-Sd (rS= –0,41 y –0,50). Error estándar de la medida: SC-Sn, 1,45; SC-Sd, 1,76. La CVRS del pacientey la del cuidador mostraron una escasa correlación con las medidas de sueño. Conclusiones. La escala SCOPA-sueño es viable, consistente y útil para evaluar el trastorno del sueño en pacientescon EP. La relación entre la CVRS y la alteración del sueño fue débil

Introduction. There is a high prevalence of sleep disorders in Parkinson’s disease (PD). Aims. To assess some basicmetric attributes of the SCOPA-Sleep scale, a measure for PD patients; secondary objective: to check the impact caused by thesleep disorder on the health-related quality of life (HRQoL) of patients and their caregivers. Subjects and methods. 68 PDpatients and their main caregivers; measures: Hoehn and Yahr staging, SCOPA-Motor, Clinical Impression of Severity Index(CISI-PD), PDSS, Hospital Anxiety and Depression Scale, SCOPA-Psychosocial, and EuroQoL. Carers filled in a PDSSquestionnaire about patient sleep and HRQoL measures (SF-36, EuroQoL). SCOPA-Sleep acceptability, scaling assumptions,internal consistency, construct validity and precision were determined. Results. SCOPA-Sleep acceptability and scalingassumptions resulted satisfactory, although the nocturnal sleep subescale (SC-Ns) showed a mild ceiling effect (22.1%) and adefective convergent validity was found for daytime sleepiness (SC-Ds) item 6. Internal consistency also was satisfactory forboth scales (alpha = 0.84 and 0.75, respectively). The correlation between SC-Ns and PDSS was high (rS = –0.70), as it wasbetween SC-Ns and PDSS questionnaire by caregiver (rS = –0.53). The corresponding coefficients with the SC-Ds gainedlower values (rS = –0.41 y –0.50). Standard error of measurement was 1.45 for the SC-Ns and 1.76 for the SC-Ds. Both,patient and caregiver HRQoL showed a loose association with the sleep measures. Conclusion. SCOPA-Sleep is a feasible,consistent, and useful scale for assessment of sleep disorder in PD patients. A weak association between sleep disorder andHRQoL was found

Early onset parkinsonism in dementia lacking distinct histopathological features.

Dementia lacking distinct histopathological features (DLDHF) belongs to the frontotemporal dementia syndromes. Behavioral, cognitive and motor symptoms are its usual clinical manifestations. However, considerable heterogeneity exists and no evident clinicopathological correlations can be performed. We report a patient who presented with a very unusual combination of behavioral abnormalities and prominent early parkinsonism progressing to a severe dementia. Pathological studies confirmed DLDHF with severe frontal and striatal neuronal loss and gliosis.

Prevalence of Parkinson's disease and other types of Parkinsonism. A door-to-door survey in Bidasoa, Spain.

OBJECTIVES: To assess the prevalence of Parkinson's disease and parkinsonism in two Spanish populations (Irun and Hondarribia, Bidasoa Region) and to compare the results with those of similar surveys. METHODS: The survey included 2000 participants aged 65 years or older in a door-to-door, three-phase design. In the screening phase we used the SNES (Sicilian Neuro-Epidemiologic Study) screening questionnaire, which has 100% sensitivity. In phases 2 and 3 we carried out a 3-year follow-up of all cases diagnosed with parkinsonism in phase 2. Progressively stricter diagnostic criteria were chosen in order to minimize the impact of false positives on the final results. RESULTS: The prevalence of Parkinson's disease (PD) was 1.5 % (95% confidence interval, 0.9 to 2.3) and the prevalence of other types of parkinsonism (OP) was 1.1 % (95% confidence interval 0.6 to 1.9). The overall prevalence by age group was 0.4 % (65-74 years), 4.7% (75-84 years), and 2.9% (> or =85 years) for Parkinson's disease and 0.7%, 2%, and 3.9 % for parkinsonism, respectively. The other parkinsonism prevalence was 1.3 % in men and 1.6 % in women. CONCLUSIONS: These prevalence rates are similar than those found in studies made in other European countries. The prevalence of both Parkinson's disease and other types of parkinsonism increased with age, with no significant differences between men and women.

The validity of Hodkinson's Abbreviated Mental Test for dementia screening in Guipuzcoa, Spain.

The objective of this research was to evaluate the validity of Hodkinson's Abbreviated Mental Test (AMT) in screening for dementia and to identify the optimum cut-off point to use in a prevalence survey. The study included two groups of persons: (i) a random sample of 183 individuals selected from census data, 96 of whom completed the study and (ii) another 36 persons with dementia were selected from a hospital outpatients department by sampling consecutive cases. The DSM-IV criteria were used as the "gold standard" to establish a diagnosis of dementia. The AMT was administered to the 132 participants who subsequently underwent independent clinical evaluation. In the community sample, 11 persons were diagnosed with dementia and 85 without. In the total sample, a score of 7 maximizes the efficacy of the test. The sensitivity for this cut-off point is 91.5% (78.7-97.2%) and the specificity is 82.4% (72.2-89.5%). A score of 9 gives 100% sensitivity, but the proportion of false positives rises to 66%. Our results are consistent with other studies and suggest that the AMT is a valid instrument for use in screening for dementia in populations similar to the one in this study.

Prevalence of essential tremor: a door-to-door survey in bidasoa, spain.

OBJECTIVES: To assess the prevalence of essential tremor (ET) in two Spanish populations (Irun and Hondarribia, Bidasoa region) and to compare the results with those of similar surveys. METHODS: The survey included 2,000 participants aged 65 years or older in a door-to-door, two-phase design. ET was defined as postural or kinetic tremor of the head or limbs. RESULTS: ET prevalence after age adjustment was 4.8% (95% confidence interval, 3.6-6.4). Prevalence increased significantly with age and there were no sex differences. CONCLUSIONS: The age-adjusted prevalence rate of ET in people 65 years old and older in Bidasoa, Spain, is close to those described in other studies using a similar design and suggest no geographical variation. ET prevalence increases with age and has a similar distribution in males and females.

Metabolism and the problem of its universalization.

Metabolism tends to be conceived either as an operationally closed network of production of components or as an autonomous apparatus of management of energy flows. Taking up some recent ideas that connect the concept of autonomy with thermodynamic requirements, we move further to defend the hypothesis that there must be a deep intertwinement between the relational-constructive logic of a basic biological system and the logic of its thermodynamic implementation. Hence, we propose that metabolism should be universally defined as the recursive self-maintenance of controls upon the energy flows necessary for the physical realization of a component production system operationally closed. Finally, being critical with some claims of the so-called 'strong' artificial life approach, we try to show that present 'computational metabolisms' are necessarily different in their structure and functioning from any real metabolic system, due to the distinct type of causal relations and mechanisms which are respectively established in them.

From records to self-description: the role played by RNA in early evolutive systems.

We study the appearance of genetic information starting from a system where self-reproductive and enzymatic functions are supported by the same sort of molecules. In a first phase, the information must have arisen in the form of rate independent sequences as records of enzymatic functions. Although this stage must have played an important role in evolution, it will be shown how its evolutive capacities were blocked by the impossibility of appearance of geno/phenotype duality. Finally, a logical scheme is proposed for a transition process toward a system with a code offering a simplification of the conditions required from the assumption of a maximum use of the double RNA capacity, both reproductive and enzymatic.

Structural limits for evolutive capacities in complex molecular systems.

The possibilities of evolution for a system with and without a code of translation from nucleic acids into proteins are evaluated. Our interest is mainly centred on the enzymatic RNA case since this molecule has, at the same time, reproductive and functional properties. After scanning the evolutive capacities of the enzymatic RNAs, including the possibility to play the role of "synthetase" which would match nucleic acids with amino acids as a transition step towards a code, we will try to show that due to their own functional limitative factors, the matching system (code) is necessary. This would be the only way to transform the formal complexity--complexity which has not entered into action before the translation process--into functional information to drive the instructive self-reproductive process. Once this stage is reached, the system could evolve without a limit.