Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.

Objective: The aim of this study is to know the prevalence of anxiety and depression in caregivers of patients with Alzheimer's disease (AD) and assess the association of caregiver burden (CB) with characteristics of both patients and caregivers. Method: Sociodemographic and clinical variables have been obtained (patients: age, gender, marital status, years of education, duration and severity of dementia, psychiatric disorders, previous history, and use of psychoactive and antidementia drugs; caregivers: age, gender, relationship with patient, and marital status). Cognition was assessed with Mini Mental State Examination (MMSE); severity of dementia was assessed with Global Deterioration Scale (GDS); caregiver burden was assessed with Hamilton Depression Rating Scale (HDRS), State-Trait Anxiety Inventory (STAI), and the number of hours of attention to the basic activities of daily-living (H-BADL). Results: More than 50% of caregivers have shown high anxiety and depression scores. Patients with longer duration of dementia, greater severity of dementia, and lower education levels significantly differ in anxiety and depression mean scores. Conclusion: The presence of CB in AD patients is strongly associated with the duration and severity of dementia and the educational level of patients. The results of this study should encourage researchers and clinicians working with elderly persons to consider these modifiable psychological states.

Background: Caregiving for people with Alzheimer's disease (AD) is highly stressful and has significant negative consequences, such as anxiety and depression. Previous research offers conflicting findings as to whether coping strategies are associated with greater psychological distress or not. We conducted this study with a view to obtaining new data regarding the association of coping strategies and psychological distress in AD caregivers.Methods: Eighty people with AD and their primary caregivers living in the community were recruited from local health services. Purposive recruitment was carried out to ensure that the sample was representative of people living with dementia in terms of dementia severity, gender, and care setting. We used the State-Trait Anxiety Inventory to measure anxiety, the Beck Depression Inventory to measure depression, and the Coping Strategies Inventory to measure coping strategies.Results: Most caregivers reported higher anxiety and depression levels. Use of disengagement coping strategies (Wald = 3.35, p = 0.01) and higher caregiver burden (Wald = 4.83, p = 0.02) predicted anxiety on logistic regression. In turn, use of disengagement coping strategies (Wald = 12.48, p = 0.001) and higher caregiver burden (Wald = 6.91, p = 0.009) predicted depression on logistic regression.Conclusion: These results may be useful for designing treatment interventions that aim to modify the use of coping strategies and thus reduces caregiver anxiety and depression.

Sleep disturbances (SDs) in Alzheimer's disease (AD) may significantly affect the behavioral, functional, and cognitive capacities of patients to the point of becoming a major determinant of caregiver burden. We conducted a cross-sectional study in 125 patients with probable AD to assess the association of SDs with neuropsychiatric symptoms, cognitive and functional status of patients, and severity and duration of dementia and to ascertain the role of antidementia drugs in the treatment of SD. SDs were assessed using the questionnaire on sleep disorders in the Neuropsychiatric Inventory. The prevalence of SDs in this sample was 36%. SDs in patients with AD are significantly associated with depression (Wald's test, 3.983; p < 0.05), disinhibition (Wald's test, 5.522; p < 0.05), and aberrant motor behavior (Wald's test, 7.430; p < 0.01). The patients treated with memantine presented lower mean SDs scores (t = 2.76; p < 0.001). These results highlight the need for a standardized and validated approach to the assessment of SDs in AD.