Subjective Cognitive and Communicative Complaints and Health-Related Quality of Life in Parkinson's Disease with and without Mild Cognitive Impairment.

INTRODUCTION: Mild Cognitive Impairment (MCI) is common in Parkinson's Disease (PD). Few studies have compared the Health-Related Quality of Life (HRQoL) in patients with and without MCI due to PD (PD-MCI), and its correlation to patients' subjective cognitive and communicative difficulties has not been explored. OBJECTIVE: We aimed to compare HRQoL in PD-MCI and PD without MCI (PD-nMCI), and explore its possible relationship to subjective cognitive and communicative complaints. METHODS: We included 29 PD-nMCI and 11 PD-MCI patients. The HRQoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39): its Cognition dimension was used as a measure of subjective cognitive complaints, its Communication dimension for subjective communicative complaints, and the summary index (PDQ-39 SI) as an indicator of HRQoL. Non-parametric partial correlations between the Cognition and Communication dimensions, and the adjusted PDQ-39 SI were conducted. RESULTS: PD-MCI patients had greater subjective cognitive and communicative complaints and worse HRQoL than PD-nMCI patients. In the PD-MCI group, both subjective cognitive and communicative complaints exhibited significant direct correlations with the adjusted HRQoL scores. CONCLUSIONS: HRQoL seems to be affected in PD-MCI, and it might be influenced by greater subjective cognitive and communicative complaints. Including patient-reported outcome measures of HRQoL, and providing cognitive and speech rehabilitation, as well as psychotherapeutic strategies to face these deficits can enhance the patient-centred approach in PD.

Mutations in SORL1 and MTHFDL1 possibly contribute to the development of Alzheimer's disease in a multigenerational Colombian Family.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 50 million people worldwide in 2020 and this number will triple to 152 million by 2050. Much of the increase will be in developing countries like Colombia. In familial forms, highly penetrant mutations have been identified in three genes, APP, PSEN1, and PSEN2, supporting a role for amyloid-ß peptide. In sporadic forms, more than 30 risk genes involved in the lipid metabolism, the immune system, and synaptic functioning mechanisms. We used whole-exome sequencing (WES) to evaluate a family of 97 members, spanning three generations, with a familiar AD, and without mutations in APP, PSEN1, or PSEN2. We sequenced two affected and one unaffected member with the aim of identifying genetic variants that could explain the presence of the disease in the family and the candidate variants were validated in eleven members. We also built a structural model to try to determine the effect on protein function. WES analysis identified two rare variants in SORL1 and MTHFD1L genes segregating in the family with other potential risk variants in APOE, ABCA7, and CHAT, suggesting an oligogenic inheritance. Additionally, the structural 3D models of SORL1 and MTHFD1L variants shows that these variants produce polarity changes that favor hydrophobic interactions, resulting in local structural changes that could affect the protein function and may contribute to the development of the disease in this family.

Subjective Cognitive and Communicative Complaints and Health-Related Quality of Life in Parkinson's Disease with and without Mild Cognitive Impairment.

INTRODUCTION: Mild Cognitive Impairment (MCI) is common in Parkinson's Disease (PD). Few studies have compared the Health-Related Quality of Life (HRQoL) in patients with and without MCI due to PD (PD-MCI), and its correlation to patients' subjective cognitive and communicative difficulties has not been explored. OBJECTIVE: We aimed to compare HRQoL in PD-MCI and PD without MCI (PD-nMCI), and explore its possible relationship to subjective cognitive and communicative complaints. METHODS: We included 29 PD-nMCI and 11 PD-MCI patients. The HRQoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39): its Cognition dimension was used as a measure of subjective cognitive complaints, its Communication dimension for subjective communicative complaints, and the summary index (PDQ-39 SI) as an indicator of HRQoL. Non-parametric partial correlations between the Cognition and Communication dimensions, and the adjusted PDQ-39 SI were conducted. RESULTS: PD-MCI patients had greater subjective cognitive and communicative complaints and worse HRQoL than PD-nMCI patients. In the PD-MCI group, both subjective cognitive and communicative complaints exhibited significant direct correlations with the adjusted HRQoL scores. CONCLUSIONS: HRQoL seems to be affected in PD-MCI, and it might be influenced by greater subjective cognitive and communicative complaints. Including patient-reported outcome measures of HRQoL, and providing cognitive and speech rehabilitation, as well as psychotherapeutic strategies to face these deficits can enhance the patient-centred approach in PD.

"In the flesh": Narratives of family caregivers at risk of Early-onset Familial Alzheimer's Disease.

In the growing body of literature dealing with the consequences of family caregiving amongst people with dementia, there are few studies examining the impact of Early-onset Familial Alzheimer's Disease on caregivers. This study exposes the subjective experience of a group of family caregivers who themselves possess a genetic susceptibility to develop this form of dementia. We interviewed and analyzed the accounts of 27 caregivers belonging to family lineages carrying the E280A mutation for Early-onset Alzheimer's Disease. We utilized a phenomenological method to analyze these accounts, initially tracking seven theoretical categories (Anxiety, Depression, Burden, Resilience, Self-efficacy, Social Support, and Coping Strategies) and then subsequently two additional categories which emerged (Conceptions about the Disease and Other Vital Experiences Interfering with Caregiving). The results show that caring for a loved one while simultaneously running the risk of developing the same form of Alzheimer's Disease permeates the caregivers' experience both in a negative and a positive way. The continuous exposition to emotional stress in these caregivers should be seriously considered as they may be at risk of accelerating the onset of symptoms of Alzheimer's Disease, while simultaneously, early psychological symptoms of dementia may be masked by the emotional sequelae of caregiving, interfering with early diagnosis. Certainly, support services for the entire family group are suggested.

Adherence/Retention Alzheimer's Prevention Initiative Colombia Plan.

INTRODUCTION: The Alzheimer's Prevention Initiative Colombia Trial is a collaborative project involving the Neurosciences Group of Antioquia, Genentech/Roche, and the Banner Alzheimer's Institute, studying whether crenezumab can delay or prevent the clinical onset of Alzheimer's disease in cognitively unimpaired individuals who carry the PSEN1 E280A mutation. In an effort to optimize participant compliance and adherence and maintain interest in the trial for its duration, the Neurosciences Group of Antioquia developed an "Adherence/Retention Plan." This plan identifies potential barriers to trial adherence related to characteristics of the participants and study partners, protocol design, sponsors, investigators, environmental factors, and characteristics of this population in general and identifies potential solutions to these barriers. METHODS: Neurosciences Group of Antioquia designed and implemented a number of strategies including a) a prescreening process that emphasized detailed and staged informed consent involving the participant and family and/or friends, b) a schedule of visits and assessments designed to minimize burden while achieving the trial's aims, c) appointment reminders, d) reimbursement for transportation and missed work, e) meals during study visits, f) birthday cards, g) quarterly newsletters, h) annual in-person feedback meetings, i) a supplemental health plan to participants, and j) a social plan to support family members. All the methods used in this plan were approved by local ethics committees. RESULTS: By the end of the fourth year of the trial, participant retention was 94.0%, with most participants reporting that they felt "very satisfied" with their participation in the trial. DISCUSSION: The Adherence/Retention Plan plays a crucial role in maintaining adherence and compliance needed to achieve the ambitious goals of the Alzheimer's Prevention Initiative-Colombia Autosomal Dominant Alzheimer's Disease Trial and may offer guideposts for other prevention trials.

Heterogeneidad sintomatológica. Perfiles de pacientes diagnosticados con demencia tipo Alzheimer en Antioquia (Colombia) / Symptomatology heterogeneity. Profiles of patients diagnosed with Alzheimer's type dementia in Antioquia (Colombia)

Resumen Objetivo: Describir y contrastar la variabilidad sintomatológica de los casos con demencia tipo Alzheimer esporádico (DTA+E) con los datos obtenidos de los casos con demencia tipo Alzheimer familiar precoz causado por la mutación E280A del Neurobanco del Grupo de Neurociencias de Antioquia (GNA). Materiales y Método: Este estudio fue de tipo exploratorio-descriptivo y correlacional, se tomaron 83 casos de donantes con DTA almacenados en el Neurobanco del GNA. Estos casos se dividen en dos grupos, i) un grupo definido genéticamente como portador de la mutación E280A en el gen de la Presenilina1; y ii) otro grupo no portador de la mutación diagnosticado con Demencia Tipo Alzheimer Esporádico (DTA+E); se contrastaron los marcadores y/o características neuropsiquiatricas, neuropsicológicas, neurológicas y neuropatológicas de ambos grupos. Resultados: El síntoma que mostró mayores diferencias entre ambos grupos fue la repetidera (DTAF E280A fue de 1.2% y el grupo de DTA+E fue 18.4%). Otros síntomas como la depresión o el tiempo de aparición de pérdida progresiva de memoria no mostraron grandes diferencias entre grupos (DTAF E2080A=55.9%; DTA+E =53.1%) y (DTAF E2080A=55.9%; DTA+E =53.1%). Los trastornos del lenguaje que se observaron con mayor frecuencia entre los donantes fueron la pérdida del lenguaje, mutismo, anomia y afasia. El signo de mayor frecuencia en ambos grupos fue descontrol de esfínteres. La atrofia se registró con mayor intensidad en los lóbulos temporales de los cerebros de los donantes con DTA +E (83.3%). Los pesos del cerebro y del contenido de la fosa posterior, tienen una relación moderada, directamente proporcional y altamente significativa desde el punto de vista estadístico. Conclusiones: Existen diferencias neuropatológicas entre DTA+E y E280A que pueden estar asociadas a la fisiopatología de la forma hereditaria de E280A.

Abstract Objective: To describe and contrast the symptomatic variability of cases with sporadic or non-sporadic Alzheimer's dementia (DTA + E) with the data obtained from the cases with early familial Alzheimer's dementia caused by the E280A of the Neurobank of the Neurosciences Group of Antioquia (GNA). Materials and Method: This study was of exploratory - descriptive and correlacional type, 83 donors' cases were taken with DTA stored in the Neurobank. These cases were divided in two groups, i) a group defined genetically like E280A; and ii) another not carrying group of the mutation (DTA+E); the scoreboards and / or characteristics neuropsychiatric, neuropsychological, neurological and neuropathological of both groups were confirmed Results: The symptom that showed higher differences between both groups was iteration (DTAF E280A with 1.2% and 18.4% for the DTA+E group). Other symptoms as depression or the time of appearance of progressive loss of memory did not show big differences among groups (DTAF E2080A=55.9%; DTA+E =53.1%) and (DTAF E2080A=55.9%; DTA+E =53.1%). The language disorders that were observed with major frequency among the donors were the loss of the language, mutism, anomia and aphasia. The sign with higher frequency in both groups was lost of sphincter control. The atrophy was with more intensity in the temporary lobes of the brains of the donors with DTA+E (83.3%). The weight of the brain and of the posterior fosse content, they have a moderate, directly proportional and highly significant relation from the statistical point of view. Conclusions: DTA +E has neuropathological differences with DTAF E280A that can be associated with the physiology hereditary from of DTAF E280A.

Tracking the Cognitive, Social, and Neuroanatomical Profile in Early Neurodegeneration: Type III Cockayne Syndrome.

Cockayne syndrome (CS) is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration, and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications, and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind, and empathy) tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language, and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions), which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor's brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging.