Early Depressive Symptoms Predict Faster Dementia Progression in Autosomal-Dominant Alzheimer's Disease.

BACKGROUND: Depression is associated with Alzheimer's disease (AD). OBJECTIVE: To evaluate the association between depressive symptoms and age of onset of cognitive decline in autosomal dominant AD, and to determine possible factors associated to early depressive symptoms in this population. METHODS: We conducted a retrospective study to identify depressive symptoms among 190 presenilin 1 (PSEN1) E280A mutation carriers, subjected to comprehensive clinical evaluations in up to a 20-year longitudinal follow-up. We controlled for the following potential confounders: APOE, sex, hypothyroidism, education, marital status, residence, tobacco, alcohol, and drug abuse. RESULTS: PSEN1 E280A carriers with depressive symptoms before mild cognitive impairment (MCI) develop dementia faster than E280A carriers without depressive symptoms (Hazard Ratio, HR = 1.95; 95% CI, 1.15-3.31). Not having a stable partner accelerated the onset of MCI (HR = 1.60; 95 % CI, 1.03-2.47) and dementia (HR = 1.68; 95 % CI, 1.09-2.60). E280A carriers with controlled hypothyroidism had later age of onset of depressive symptoms (HR = 0.48; 95 % CI, 0.25-0.92), dementia (HR = 0.43; 95 % CI, 0.21-0.84), and death (HR = 0.35; 95 % CI, 0.13-0.95). APOEɛ2 significantly affected AD progression in all stages. APOE polymorphisms were not associate to depressive symptoms. Women had a higher frequency and developed earlier depressive symptoms than men throughout the illness (HR = 1.63; 95 % CI, 1.14-2.32). CONCLUSION: Depressive symptoms accelerated progress and faster cognitive decline of autosomal dominant AD. Not having a stable partner and factors associated with early depressive symptoms (e.g., in females and individuals with untreated hypothyroidism), could impact prognosis, burden, and costs.

Síntomas de depresión y calidad de vida relacionada con la salud en personas mayores: una revisión / Depression symptoms and health-related quality of life in older people: a review

Resumen. El objetivo de este estudio fue sintetizar la evidencia de la literatura científica sobre la calidad de vida relacionada con la salud (CVRS) en las personas mayores con síntomas de depresión. Se realizó una revisión sistemática de la literatura científica publicada entre 2015 y 2020 en las bases de datos Pubmed, Scielo y Scopus. Se incluyeron 35 artículos en los cuales se reportó una estrecha relación entre la calidad de vida relacionada con la salud y los síntomas de depresión, mediada por condiciones físicas y psicosociales entre las cuales se encuentran tener enfermedades crónicas, dolor persistente, comorbilidades, disminución de la independencia, bajos ingresos, alto porcentaje de grasa corporal, sedentarismo, vivir solo, pertenecer al género femenino y carecer de cuidadores empáticos. En conclusión, las personas mayores con presencia de síntomas depresivos reportan en general menor CVRS. Los hallazgos de este estudio son un aporte a la comprensión de la relación entre CVRS y depresión en la población adulta mayor en diferentes contextos, además, el estudio puede aportar evidencia importante para las intervenciones clínicas enfocadas en los aspectos emocionales de los pacientes con diferentes patologías.

Abstract. This study aimed to synthesize the scientific evidence on health-related quality of life in older people with symptoms of depression. This systematic review included studies published between 2015 and 2020. We used Pubmed, Scielo, and Scopus search engines. We included a total of 35 articles that addressed the relationship between health-related quality of life and symptoms of depression. Furthermore, those studies selected included the analysis of variables such as physical psychosocial and socioeconomic conditions, and comorbidities such as chronic diseases, persistent pain, decreased independence, high body fat percentage, sedentary lifestyle, living alone, belonging to the female gender, and lacking empathetic caregivers. Our findings show that older people with depressive symptoms generally report lower HRQoL. This study contributes to understanding the relationship between HRQL and depression in older persons in different contexts, in addition, the study can provide important evidence for clinical interventions focused on the emotional aspects of patients with different pathologies.

Specific Abnormalities in White Matter Pathways as Interface to Small Vessels Disease and Cognition in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Individuals.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by leukoencephalopathy leading to cognitive impairment. Subtle cognitive deficits can be observed early in the course of the disease, before the occurrence of the first stroke. Therefore, markers that can predict disease progression at this early stage, when interventions are likely to alter disease course, are needed. We aimed to examine the biological cascade of microstructural and macrostructural white matter (WM) abnormalities underlying cognitive deficits in CADASIL. Methods: We examined 20 nondemented CADASIL mutation carriers and 23 noncarriers who underwent neuropsychological evaluation and magnetic resonance imaging. Using probabilistic tractography of key WM tracts, we examined group differences in diffusivity measures and WM hyperintensity volume. Successive mediation models examined whether tract-specific WM abnormalities mediated subtle cognitive differences between CADASIL mutation carriers and noncarriers. Results: The largest effect size differentiating the two groups was observed for left superior longitudinal fasciculus-temporal (SLFt) diffusivity (Cohen's f = 0.49). No group differences were observed with a global diffusion measure. These specific microstructural differences in the SLFt were associated with higher WM hyperintensities burden, and subtle executive deficits in CADASIL mutation carriers. Discussion: Worse diffusivity in the left SLFt is related to greater severity of small vessel disease and worse executive functioning in the asymptomatic stage of the disease. Worse diffusivity of the left SLFt may potentially hold promise as an indicator of disease progression. Impact statement Diffusion tensor imaging outperforms conventional imaging of subcortical small vessel disease as a potential marker of future disease progression. Here we identified the left superior longitudinal temporal fasciculus as a critical white matter fiber bundle, of which worse diffusivity can link presence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy mutations to greater severity of small vessel disease and worse executive functioning in asymptomatic stages of the disease. This tract may hold promise and deserves further examination as an early indicator of disease progression.

Global Cardiovascular Risk Profile and Cerebrovascular Abnormalities in Presymptomatic Individuals with CADASIL or Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Cardiovascular risk factors increase the risk of developing dementia, including Alzheimer's disease and vascular dementia. OBJECTIVE: Studying individuals with autosomal dominant mutations leading to the early onset of dementia, this study examines the effect of the global cardiovascular risk profile on early cognitive and neuroimaging features of Alzheimer's disease and vascular dementia. METHODS: We studied 85 non-demented and stroke-free individuals, including 20 subjects with Presenilin1 (PSEN1) E280A mutation leading to the early onset of autosomal dominant Alzheimer's disease (ADAD), 20 subjects with NOTCH3 mutations leading to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to the early onset of vascular dementia, and 45 non-affected family members (non-carriers). All subjects underwent clinical and neuropsychological evaluations and an MRI. The global cardiovascular risk profile was estimated using the office-based Framingham Cardiovascular Risk Profile (FCRP) score. RESULTS: In individuals with CADASIL, a higher FCRP score was associated with a reduced hippocampal volume (B = -0.06, p < 0.05) and an increased severity of cerebral microbleeds (B = 0.13, p < 0.001), lacunes (B = 0.30, p < 0.001), and perivascular space enlargement in the basal ganglia (B = 0.50, p < 0.05). There was no significant association between the FCRP score and neuroimaging measures in ADAD or non-carrier subjects. While the FCRP score was related to performance in executive function in non-carrier subjects (B = 0.06, p < 0.05), it was not significantly associated with cognitive performance in individuals with CADASIL or ADAD. CONCLUSION: Our results suggest that individuals with CADASIL and other forms of vascular cognitive impairment might particularly benefit from early interventions aimed at controlling cardiovascular risks.

Efectos de un programa de estimulación cognitiva en la memoria operativa en pacientes con deterioro cognitivo leve amnésico / Effects of a cognitive stimulation program in working memory in patients with amnestic mild cognitive impairment

Introducción: El deterioro cognitivo leve (DCL) es una condición intermedia entre el envejecimiento normal y la demencia. Este estudio propone la aplicación de un programa de estimulación cognitiva multifactorial (PECM), para establecer la naturaleza de los cambios que se pudieran inducir en la memoria operativa (MO) de un grupo de mujeres mayores con DCL de tipo amnésico (DCL-A). Pacientes y Métodos: Se seleccionó a conveniencia una muestra de 7 mujeres con diagnóstico de DCL-A, a quienes se les hizo mediciones neuropsicológicas y de MO antes y después de 24 sesiones de un PECM, de una hora cada una, con una frecuencia de tres veces por semana. Para medir la MO se uso la batería para la evaluación de la memoria operativa de Pickering, Baqués y Gathercole. Resultados: Se hallaron diferencias estadísticamente significativas (p<0.05) y clínicamente importantes (TE>0.75), en componentes de la MO, especialmente de la agenda visoespacial (AV) y del ejecutivo central (EC). Conclusiones: Un PECM mejora los componentes de la AV y del EC de la MO en mujeres con DCL-A. Hay una tendencia similar en el bucle fonológico, pero el tamaño pequeño de la muestra no pudo descartar la hipótesis nula.

Introduction: Mild cognitive impairment (MCI) is considered as an intermediate status between normal aging and dementia. This study proposes the administration of a program of cognitive multifactor stimulation (PCMS), toestablish the changes on Working Memory (WM) in an elderly female group with amnesic type MCI (A-MCI). Patients and Methods: A sample of seven females over sixty years old with A-MCI, which were assessed for neuropsychological function and WM, before and after a 24 sessions of one hour PCMS, three times per week. To measure WM was used the Pickering, Baqués and Gathercole’ s battery. Results: Statistically significant differences (p < 0,05) and clinically important findings (effect sizes > 0,75) on WM components, specially on visual loop (VL) and central executive (CE). Conclusion: A PCMS improved the VL and CE components of WM in seven elderly females with AMCI. The phonologic loop had a similar tendency, but the small sample size did not allow rejecting the null hypothesis.