Effect of Transcranial Pulse Stimulation for the Treatment of Alzheimer´s Disease and its Related Symptoms.

Alzheimer's disease (AD) is the most common cause of neurodegenerative cognitive impairment. Brain stimulation techniques based on the delivery of transcranial shockwaves are currently being studied for their increasing popularity as an approach to modulate the human brain in a focal and targeted manner making this therapy a promising line of action against AD. In the present manuscript, we review for further understanding whether transcranial pulse stimulation (TPS) is a beneficial treatment for AD patients. PubMed, Google Scholar, and Cochrane databases were accessed with the search criteria set from year 2001 to 2022 and the following keywords were used: "transcranial pulse stimulation", "focused ultrasound", "noninvasive treatment and Alzheimer" and "TPS". The search was focused on papers that provide evidence on the biological bases of the method, as well as its safety and tolerability. Even though more studies are needed with greater scientific rigor, such as a doubleblind and randomized study versus a placebo, TPS is an excellent and safe therapeutic option for AD. This novel approach accompanies currently available treatments and complements them, helping to maintain greater stability of the disease and slowing its progression. The biological effects and potential mechanisms of action of TPS for the improvement of cognitive function are further discussed.

Spanish consortium for ageing normative data (scand): screening tests (mmse, gds-15 and mfe) / Consorcio Español para la Obtención de Datos Normativos del Envejecimiento: Pruebas de Cribado (MMSE, GDS-15 y MFE)

BACKGROUND: Detecting cognitive impairment is a priority for health systems. The aim of this study is to create normative data on screening tests (MMSE, GDS and MFE) for middle-aged and older Spanish adults, considering the effects of sociodemographic factors. METHOD: A total of 2,030 cognitively intact subjects who lived in the community, aged from 50 to 88 years old, participated voluntarily in SCAND consortium studies. The statistical procedure included the conversion of percentile ranges into scalar scores. Secondly, the effects of age, educational level and gender were verified. Linear regressions were used to calculate the scalar adjusted scores. Cut-off values for each test were also calculated. RESULTS: Scalar scores and percentiles corresponding to MMSE, GDS-15 and MFE are shown. An additional table is provided which shows the points that must be added or subtracted from MMSE score depending on the subject's educational level. CONCLUSIONS: The current norms should provide clinically useful data for evaluating Spanish people aged 50 to 88 years old and should contribute to improving the detection of initial symptoms of cognitive impairment in people living in the community, taking into account the influence of gender, age and educational level

ANTECEDENTES: detectar el deterioro cognitivo es una prioridad del sistema sanitario. El objetivo de este estudio es la presentación de datos normativos de pruebas de cribado (MMSE, GDS y MFE) para adultos españoles de mediana edad y adultos mayores, considerando los efectos de factores sociodemográficos. MÉTODO: en los estudios realizados por el consorcio SCAND participaron voluntariamente 2.030 personas cognitivamente sanas, de 50 a 88 años, residentes en su comunidad. El procedimiento estadístico supuso la conversión de rangos percentiles en puntuaciones escalares. Posteriormente, se comprobaron los efectos de la edad, el nivel educativo y el género. Se utilizaron regresiones lineales para calcular las puntuaciones escalares ajustadas. También se calcularon los puntos de corte para cada prueba. RESULTADOS: se muestran las puntuaciones escalares y los percentiles correspondientes a MMSE, GDS-15 y MFE. Además, se presenta una tabla que muestra los puntos que deben sumarse o restarse a la puntuación del MMSE dependiendo del nivel educativo del individuo. CONCLUSIONES: los datos normativos presentados tienen una utilidad clínica para evaluar a población española de 50 a 88 años, y contribuyen a mejorar la detección de los síntomas iniciales del deterioro cognitivo teniendo en cuenta la influencia del género, la edad y el nivel educativo

Selecting the most important self-assessed features for predicting conversion to mild cognitive impairment with random forest and permutation-based methods.

Alzheimer's Disease is a complex, multifactorial, and comorbid condition. The asymptomatic behavior in the early stages makes the identification of the disease onset particularly challenging. Mild cognitive impairment (MCI) is an intermediary stage between the expected decline of normal aging and the pathological decline associated with dementia. The identification of risk factors for MCI is thus sorely needed. Self-reported personal information such as age, education, income level, sleep, diet, physical exercise, etc. is called to play a key role not only in the early identification of MCI but also in the design of personalized interventions and the promotion of patients empowerment. In this study, we leverage a large longitudinal study on healthy aging in Spain, to identify the most important self-reported features for future conversion to MCI. Using machine learning (random forest) and permutation-based methods we select the set of most important self-reported variables for MCI conversion which includes among others, subjective cognitive decline, educational level, working experience, social life, and diet. Subjective cognitive decline stands as the most important feature for future conversion to MCI across different feature selection techniques.

MAPT H1 Haplotype is Associated with Late-Onset Alzheimer's Disease Risk in APOEɛ4 Noncarriers: Results from the Dementia Genetics Spanish Consortium.

The MAPT H1 haplotype has been linked to several disorders, but its relationship with Alzheimer's disease (AD) remains controversial. A rare variant in MAPT (p.A152T) has been linked with frontotemporal dementia (FTD) and AD. We genotyped H1/H2 and p.A152T MAPT in 11,572 subjects from Spain (4,327 AD, 563 FTD, 648 Parkinson's disease (PD), 84 progressive supranuclear palsy (PSP), and 5,950 healthy controls). Additionally, we included 101 individuals from 21 families with genetic FTD. MAPT p.A152T was borderline significantly associated with FTD [odds ratio (OR) = 2.03; p = 0.063], but not with AD. MAPT H1 haplotype was associated with AD risk (OR = 1.12; p = 0.0005). Stratification analysis showed that this association was mainly driven by APOE ɛ4 noncarriers (OR = 1.14; p = 0.0025). MAPT H1 was also associated with risk for PD (OR = 1.30; p = 0.0003) and PSP (OR = 3.18; p = 8.59 × 10-8) but not FTD. Our results suggest that the MAPT H1 haplotype increases the risk of PD, PSP, and non-APOE ɛ4 AD.

The Vallecas Project: A Cohort to Identify Early Markers and Mechanisms of Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD) is a major threat for the well-being of an increasingly aged world population. The physiopathological mechanisms of late-onset AD are multiple, possibly heterogeneous, and not well understood. Different combinations of variables from several domains (i.e., clinical, neuropsychological, structural, and biochemical markers) may predict dementia conversion, according to distinct physiopathological pathways, in different groups of subjects. METHODS: We launched the Vallecas Project (VP), a cohort study of non-demented people aged 70-85, to characterize the social, clinical, neuropsychological, structural, and biochemical underpinnings of AD inception. Given the exploratory nature of the VP, multidimensional and machine learning techniques will be applied, in addition to the traditional multivariate statistical methods. RESULTS: A total of 1169 subjects were recruited between October 2011 and December 2013. Mean age was 74.4 years (SD 3.9), 63.5% of the subjects were women, and 17.9% of the subjects were carriers of at least one ε4 allele of the apolipoprotein E gene. Cognitive diagnoses at inclusion were as follows: normal cognition 93.0% and mild cognitive impairment (MCI) 7.0% (3.1% amnestic MCI, 0.1% non-amnestic MCI, 3.8% mixed MCI). Blood samples were obtained and stored for future determinations in 99.9% of the subjects and 3T magnetic resonance imaging study was conducted in 89.9% of the volunteers. The cohort is being followed up annually for 4 years after the baseline. CONCLUSION: We have established a valuable homogeneous single-center cohort which, by identifying groups of variables associated with high risk of MCI or dementia conversion, should help to clarify the early physiopathological mechanisms of AD and should provide avenues for prompt diagnosis and AD prevention.

Combined Alzheimer's disease and cerebrovascular staging explains advanced dementia cognition.

INTRODUCTION: The absence of a consensus system for full neuropathological evaluation limits clinicopathological studies and comparability between laboratories. Combined staging for Alzheimer's type and cerebral vascular pathology may allow a better classification of cases for clinical and cognitive correlation. METHODS: Cognitive and postmortem neuropathological data were obtained from 70 brains donated to the Tissue Bank of the Centro de Investigación de Enfermedades Neurológicas (CIEN) Foundation according to recently developed staging schemes for Alzheimer's type and vascular pathology. Subjects belonged to a cohort of institutionalized patients with moderate or severe dementia and a mean follow-up period of 7 years. RESULTS: Cases were classified into three groups: Alzheimer's predominant (64.1%), vascular predominant (6.3%) and mixed pathology (29.6%). Significant differences were observed in Severe Mini-Mental State Examination and verbal fluency between the vascular predominant and the other groups of patients. DISCUSSION: The combination of scales measuring cerebral vascular and Alzheimer's type pathology allowed a classification of patients that reveals differences between groups in premortem cognitive features.

Efecto de los fármacos anticolinérgicos en el rendimiento cognitivo de las personas mayores / Effect of anticholinergic drugs on cognitive impairment in the elderly

El empleo de fármacos anticolinérgicos es frecuente en personas mayores, incluso con deterioro cognitivo. Se ha realizado una revisión bibliográfica en PubMed (anticholinergic effects y anticholinergic and dementia) acerca de los efectos de los fármacos anticolinérgicos en población anciana. Se ha enfatizado en determinar patrones de consumo, uso combinado con fármacos inhibidores de la acetilcolinesterasa (IACE), medida de la carga anticolinérgica y efectos cognitivos a corto y a largo plazo. Las conclusiones son que estos fármacos se emplean de forma habitual en población anciana, incluso tras la prescripción de IACE en la enfermedad de Alzheimer. Su empleo puede producir alteraciones cognitivas. Si el consumo es prolongado puede provocar un empeoramiento de la cognición a largo plazo originando falsos diagnósticos de deterioro, o incluso precipitando cuadros de demencia. Los efectos cognitivos son mayores ante un déficit preexistente, pero desaparecen en la demencia avanzada. La presencia de ApoE ¿4 marca una vulnerabilidad a la afectación cognitiva por estos fármacos (AU)

The use of anticholinergic drugs is common in the elderly, even in people with cognitive impairment. A systematic search was conducted in PubMed (anticholinergic effects, anticholinergic and dementia) to define the effects of anticholinergic drugs in the elderly. We emphasized the search in patterns of use, the combined use with AChEIs, the measurement of the Serum Anticholinergic Activity, and the short-term and long-term cognitive effects. The conclusions are that the use of anticholinergic drugs is common in the elderly, even more so than the medical prescription of AChEIs in Alzheimer‘s disease. The use of anticholinergic drugs may result in cognitive impairment. In long-term use it may generate a worsening of cognitive functions. It can lead to a wrong diagnosis of mild cognitive impairment or dementia, and they can also initiate signs of dementia. Greater cognitive effects appear when there is a previous deficit, but cognitive effects from anticholinergic drugs disappear in severe dementia. The presence of ApoE ¿4 increases the vulnerability for cognitive impairment when these drugs are employed (AU)

[Effect of anticholinergic drugs on cognitive impairment in the elderly]. / Efecto de los fármacos anticolinérgicos en el rendimiento cognitivo de las personas mayores.

The use of anticholinergic drugs is common in the elderly, even in people with cognitive impairment. A systematic search was conducted in PubMed (anticholinergic effects, anticholinergic and dementia) to define the effects of anticholinergic drugs in the elderly. We emphasized the search in patterns of use, the combined use with AChEIs, the measurement of the Serum Anticholinergic Activity, and the short-term and long-term cognitive effects. The conclusions are that the use of anticholinergic drugs is common in the elderly, even more so than the medical prescription of AChEIs in Alzheimer's disease. The use of anticholinergic drugs may result in cognitive impairment. In long-term use it may generate a worsening of cognitive functions. It can lead to a wrong diagnosis of mild cognitive impairment or dementia, and they can also initiate signs of dementia. Greater cognitive effects appear when there is a previous deficit, but cognitive effects from anticholinergic drugs disappear in severe dementia. The presence of ApoEɛ4 increases the vulnerability for cognitive impairment when these drugs are employed.

Contribución de la patología vascular a la correlación clínico-patológica en una serie de casos de demencia avanzada / Vascular pathology's contribution to the clinical-pathological correlation in advanced dementia

Fundamento y objetivo: la enfermedad de Alzheimer (EA) se acompaña frecuentemente de patología vascular (PV). La utilización de un sistema de clasificación que combine ambos tipos de patología permitiría realizar un diagnóstico diferencial preciso. En el presente trabajo se aplican de manera conjunta criterios neuropatológicos de EA y PV para clasificar una cohorte de pacientes con demencia avanzada. Material y método: se analizaron los datos neuropatológicos post mórtem de 40 cerebros donados al Banco de Tejidos de la Fundación CIEN. Todos los sujetos eran mayores de 70 años (edad = 85,42 ± 7,06; 75 % mujeres) y residentes del Centro Alzheimer de la Fundación Reina Sofía. Resultados: EA y PV no mostraron ninguna relación entre sí. Las puntuaciones cognitivas correlacionaron de forma inversamente proporcional con la EA, pero no mostraron asociación con la PV. Utilizando una escala de EA y otra de PV, los casos se clasificaron en tres grupos (57,5% EA, 12,5 % demencia vascular y 30 % demencia mixta) y se estudió su rendimiento en los test cognitivos. Conclusiones: el grupo vascular evidenció un rendimiento cognitivo superior a los otros dos. Los resultados apoyan el uso combinado de escalas de EA y PV para clasificar a los pacientes con demencia avanzada (AU)

Introduction and aim: Alzheimer’s (AD) disease is often accompanied by vascular pathology (VP). The use of a classification system combining both types of pathologies would enable a precise differential diagnosis. In this paper neuropathological criteria of AD and VP are applied in order to classify a cohort of patients with advanced dementia. Material and method: Postmortem neuropathological data from 40 brains donated to the CIEN Foundation Bank Tissue were analyzed. All participants were over 70 years old (mean age = 85.42 ± 7.06; 75% women) and they were institutionalized at the Alzheimer Center Reina Sofia Foundation. Results: AD and VP did not show any relation between them. Cognitive scores correlated inversely proportional with AD, but no association with VP was found. Combination of both scales allowed a classification of cases in three groups (57.5% AD, 12.5% vascular dementia, and 30% mixed dementia). Cognitive performance of those groups was studied. Discussion: Vascular group showed a higher cognitive performance than the other two groups. These results support the combination of AD and VP scales to classify a cohort of patients with advanced dementia (AU)

El lenguaje en el envejecimiento: procesos de recuperación léxica / Language in aging: lexical retrieval processes

En los últimos años, ha existido un interés creciente por entender la naturaleza del lenguaje en el envejecimiento, no solo por tratar de describir el modo en que este dominio cambia con la edad, sino también por la particular cualidad que su complejidad e interdependencia con otros procesos cognitivos le confieren sirviendo de marco en el desarrollo de teorías generales sobre el envejecimiento, al tiempo que brindando la oportunidad de examinar los sustratos neurobiológicos asociados al deterioro funcional y la preservación cognitiva. Aunque el procesamiento lingüístico parece resistir el avance de la edad, lo cierto es que cambios asociados al proceso de envejecimiento surgen también en el lenguaje. Sin embargo, el envejecimiento no afecta al lenguaje de un modo global, sino específicamente produciendo asimetrías, entre las que destaca un marcado deterioro de la producción frente a un relativo mantenimiento de la comprensión o un aumento del vocabulario. El propósito de este trabajo es revisar los principales cambios estructurales y funcionales que acontecen en el cerebro con la edad, así como los declives que a nivel cognitivo de ellos se derivan, con particular interés en el efecto que estos cambios pueden tener en el lenguaje, y en especial en los procesos de recuperación léxica. Se considera también el efecto de factores sociales, tales como el nivel educativo y la posición socioeconómica. El artículo aborda además los déficits de acceso léxico asociados a enfermedad neurológica, concretamente a deterioro cognitivo leve y enfermedad de Alzheimer (AU)

In the last few years, interest in understanding the nature of language in aging has grown. This interest concerns how this domain changes with age. Furthermore, because of its complexity and interdependence with other cognitive processes, language provides a framework to develop general theories on aging and to examine the neurobiological substrates in relation to functional impairment and cognitive preservation. Although linguistic processes seem not to be impaired as a result of age, age-related changes do affect language. However, not all linguistic processes are affected equally. Aging causes a marked deterioration in language production versus a relative preservation of comprehension or an increase in vocabulary. The aim of this study was to review age-related changes in brain structure and function, as well as the resulting cognitive decline, with particular focus on the effect that these changes might have on language, especially on the processes of lexical retrieval. The role of social variables, such as education and socioeconomic status are also considered. Deficits in lexical access related to neurological disorders such as mild cognitive impairment and Alzheimer's disease are also discussed (AU)