Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study

Abstract Background Neuroimaging studies of autosomal dominant Alzheimer’s disease (ADAD) enable characterization of the trajectories of cerebral amyloid-β (Aβ) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD. Methods Fourteen ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2–3 sessions of Aβ (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2–4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers. Results Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with Aβ accumulation (16 years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (~ 9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers. Conclusions Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between Aβ burden and neocortical tau accumulation in ADAD.

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Nutritional assessment in patients with early-onset Autosomal Dominant Alzheimer’s Disease due to PSEN1- E280A genetic variant: a cross-sectional study

Journal of Aging Research and Lifestyle ◽

10.14283/jarlife.2021.6 ◽

2021 ◽

pp. 1-7

Author(s):

M. Gómez-Vega ◽

E. Garcia-Cifuentes ◽

D. Aguillon ◽

J.E. Velez ◽

A. Jaramillo-Jimenez ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Nutritional Status ◽

Early Onset ◽

Autosomal Dominant ◽

Nutritional Assessment ◽

Mini Nutritional Assessment ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional

Background: Weight loss and malnutrition are frequent findings in late-onset and sporadic presentations of Alzheimer’s Disease (AD). However, less is known about nutritional status in Early-Onset Autosomal Dominant AD (EO-ADAD). Objective: To analyze the association between nutritional status and other clinical and sociodemographic characteristics in individuals with a genetic form of EO-ADAD. Design, settings, and participants: Cross-sectional study with 75 non-institutionalized participants from a cohort of Autosomal Dominant AD (13 with mild cognitive impairment and 61 with dementia, ages from 38 to 67 years) underwent a structured clinical assessment with emphasis on nutritional status. Measurements: Primary outcome was nutritional status and it was measured using the Mini Nutritional Assessment (MNA). Patients were categorized according to MNA total score, as undernourished (MNA ≤23.5) and well-nourished (MNA ≥ 24). Sociodemographic and clinical variables identified as potential predictors or confounders of nutritional status were also collected. Results: Undernourishment by MNA was present in 57.3% of the sample. Forty-two percent of participants had abnormal BMI values considered lower than 18.5 or higher than 24.9 kg/m2. Total BMI values were similar in well and undernourished patients (median 24.2 IQR 3.59 and median 23.9 IQR 4.42, respectively, p=0.476). When comparing well and undernourished groups, we found statistically significant differences for variables: severity of dementia (p=0.034), frailty (p=0.001), multimorbidity (p=0.035) and, polymedication (p=0.045). Neither adjusted logistic regression nor the Poisson regression showed that any clinical or sociodemographic variables explained undernourishment. Conclusions: Undernourishment was a frequent finding in our sample of EO-ADAD, especially in later stages of the disease. Patients with polymedication, multimorbidity, frailty and severe dementia show differences in their nutritional status with a tendency to be more frequently undernourished. Further studies with larger sample sizes are needed to establish this association.

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Perceived stress and depressive symptoms not neuropsychiatric symptoms predict caregiver burden in Alzheimer’s disease: a cross-sectional study

BMC Geriatrics ◽

10.1186/s12877-021-02136-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Manee Pinyopornpanish ◽

Kanokporn Pinyopornpanish ◽

Atiwat Soontornpun ◽

Surat Tanprawate ◽

Angkana Nadsasarn ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Depressive Symptoms ◽

Caregiver Burden ◽

Perceived Stress ◽

Neuropsychiatric Symptoms ◽

Cross Sectional Study ◽

Assessment Tools ◽

Sectional Study ◽

Cross Sectional

Abstract Background Caregiver burden affects the caregiver’s health and is related to the quality of care received by patients. This study aimed to determine the extent to which caregivers feel burdened when caring for patients with Alzheimer’s Disease (AD) and to investigate the predictors for caregiving burden. Methods A cross-sectional study was conducted. One hundred two caregivers of patients with AD at Maharaj Nakorn Chiang Mai Hospital, a tertiary care hospital, were recruited. Assessment tools included the perceived stress scale (stress), PHQ-9 (depressive symptoms), Zarit Burden Interview-12 (burden), Clinical Dementia Rating (disease severity), Neuropsychiatric Inventory Questionnaires (neuropsychiatric symptoms), and Barthel Activities Daily Living Index (dependency). The mediation analysis model was used to determine any associations. Results A higher level of severity of neuropsychiatric symptoms (r = 0.37, p < 0.01), higher level of perceived stress (r = 0.57, p < 0.01), and higher level of depressive symptoms (r = 0.54, p < 0.01) were related to a higher level of caregiver burden. The direct effect of neuropsychiatric symptoms on caregiver burden was fully mediated by perceived stress and depressive symptoms (r = 0.13, p = 0.177), rendering an increase of 46% of variance in caregiver burden by this parallel mediation model. The significant indirect effect of neuropsychiatric symptoms by these two mediators was (r = 0.21, p = 0.001). Conclusion Caregiver burden is associated with patients’ neuropsychiatric symptoms indirectly through the caregiver’s depressive symptoms and perception of stress. Early detection and provision of appropriate interventions and skills to manage stress and depression could be useful in reducing and preventing caregiver burden.

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Frequency and Severity of Adverse Drug Reactions to Medications Prescribed for Alzheimer’s Disease in a Brazilian City: Cross-Sectional Study

Frontiers in Pharmacology ◽

10.3389/fphar.2020.538095 ◽

2020 ◽

Vol 11 ◽

Author(s):

Tânia Regina Ferreira ◽

Luciane Cruz Lopes ◽

Cristiane de Càssia Bergamaschi

Keyword(s):

Public Health ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Health System ◽

Psychiatric Disorders ◽

Public Health System ◽

Cross Sectional Study ◽

Sectional Study ◽

Drug Reactions ◽

Cross Sectional

Background: There is lack of national studies that assess the risks associated with the drugs provided under the Brazilian public health system for treating Alzheimer’s disease. Then, this study determined the prevalence and severity of self-reported adverse drug reactions (ADRs) prescribed to patients with Alzheimer’s disease in the Brazilian public health system.Methods: A cross-sectional study was carried out based on public data from the MEDEX system (information on dispensing data, known as exceptional dispensing medications) and interviews with patients and/or caregivers who get access to Alzheimer’s drugs at a public pharmacy in a large Brazilian city, between July and September 2017, inquiring about ADRs and serious adverse events (SAEs).Results: The subjects were asked about ADRs and SAEs related to the use of donepezil, galantamine, rivastigmine and memantine. Out of 285 patients enrolled on the database, 250 participated in the study (87.7%). Among the participants, approximately 63.0% were female, 70.3% aged ≥75 years and 70.3% had comorbidities. Overall, 209 patients (83.6%) reported at least one ADR (total 1,149 ADRs) and rivastigmine was associated with the largest number of ADRs per patient (7.9 ADRs/patient). The predominant adverse effects were psychiatric disorders with common frequency (57.1%) and mild severity (89.0%). Six patients (2.4%) had SAEs that required hospitalization. The use of antipsychotics was the variable associated with ADR (OR = 4.95; 95% CI: 1.45–16.93; p = 0.011).Conclusion: There was a large number of reported ADRs and most of them were of common frequency and mild severity, being mainly related to psychiatric disorders. Considering the fragility of these patients, it is important to improve safety-related care in the use of drugs for treating this disease.

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