Family experience of young-onset dementia: the perspectives of spouses and children.

OBJECTIVES: Although young-onset dementia (YOD) affects the whole family system, this population is still under-represented in literature, and no progress in care provision has been made. Hence, additional evidence is necessary to understand how family and social relationships are affected by YOD and care challenges, as to provide recommendations for clinical practice and service improvement from a family perspective. METHOD: Family carers were recruited via one memory clinic and the local Alzheimer's Associations in Italy. Semi-structured interviews explored their experiences with YOD, the impact of the condition on their lives, family and social relationships, and the support and care they received. Transcripts were coded by three researchers and analysed using inductive thematic analysis. RESULTS: Thirty-eight interviews were conducted with 26 spouses and 12 adult children. Three themes emerged: 1) Problems around diagnosis, 2) Lack of post-diagnostic support, and 3) Living with YOD as a family. Overall, problems occurred across the dementia pathway. Without appropriate support, it was difficult for families to adjust to living with YOD and to the associated changes in family roles and relationships. CONCLUSIONS: Since optimal care depends on good family relationships, better support for families in the adaptation to condition would likely benefit patient care while ensuring social inclusion and health equity for vulnerable groups.

Dementia-related genetic variants in an Italian population of early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) is the most common form of early-onset dementia. Although three major genes have been identified as causative, the genetic contribution to the disease remains unsolved in many patients. Recent studies have identified pathogenic variants in genes representing a risk factor for developing Alzheimer's disease (AD) and in causative genes for other degenerative dementias as responsible for EOAD. To study them further, we investigated a panel of candidate genes in 102 Italian EOAD patients, 45.10% of whom had a positive family history and 21.74% with a strong family history of dementia. We found that 10.78% of patients carried pathogenic or likely pathogenic variants, including a novel variant, in PSEN1, PSEN2, or APP, and 7.84% showed homozygosity for the ε4 APOE allele. Additionally, 7.84% of patients had a moderate risk allele in PSEN1, PSEN2, or TREM2 genes. Besides, we observed that 12.75% of our patients carried only a variant in genes associated with other neurodegenerative diseases. The combination of these variants contributes to explain 46% of cases with a definite familiarity and 32% of sporadic forms. Our results confirm the importance of extensive genetic screening in EOAD for clinical purposes, to select patients for future treatments and to contribute to the definition of overlapping pathogenic mechanisms between AD and other forms of dementia.

Educational interventions to improve detection and management of cognitive decline in primary care-An Italian multicenter pragmatic study.

Introduction: Timely detection of cognitive decline in primary care is essential to promote an appropriate care pathway and enhance the benefits of interventions. We present the results of a study aimed to evaluate the effectiveness of an educational intervention addressed to Italian family physicians (FPs) to improve timely detection and management of cognitive decline. Materials and methods: We conducted a pre-post study in six Italian health authorities (HAs) involving 254 FPs and 3,736 patients. We measured process and outcome indicators before the intervention (1 January 2014 to 31 December 2016) and after the intervention (1 January 2018 to 31 December 2019). One interactive face-to-face session workshop was delivered by local cognitive disorders and dementia specialists and FP advisors at each HA, in the period September 2017-December 2017. The session focused on key messages of the local Diagnostic and Therapeutic Care Pathway (DTCP) or regional guidelines: (a) the role of the FP for a timely suspicion of cognitive decline is fundamental; (b) when cognitive decline is suspected, the role of the FP is active in the diagnostic work-up; (c) FP's knowledge on pharmacological and non-pharmacological interventions is essential to improve the management of patients with cognitive decline. Results: An overall improvement in diagnostic procedures and management of patients with cognitive decline by FPs after the intervention was observed. The number of visits per year performed by FPs increased, and the time interval between the first FP consultation and the diagnosis was optimized. Neuroleptic use significantly decreased, whereas the use of benzodiazepines remained steadily high. Non-pharmacological interventions, or use of support services, were underrepresented even in the post-intervention. Differences among the participating HAs were identified and discussed. Discussion: Results from this study suggest the success of the educational intervention addressed to FPs in improving early detection and management of cognitive decline, highlighting the importance to continue medical education in this field. At the same time, further initiatives of care pathway dissemination and implementation should promote strategies to enhance interactions between primary and secondary care optimizing the collaboration between FPs and specialists.

Identification of rare genetic variants in Italian patients with dementia by targeted gene sequencing.

Genetics is intricately involved in the etiology of neurodegenerative dementias. The incidence of monogenic dementia among all neurodegenerative forms is unknown due to the lack of systematic studies and of patient/clinician access to extensive diagnostic procedures. In this study, we conducted targeted sequencing in 246 clinically heterogeneous patients, mainly with early-onset and/or familial neurodegenerative dementia, using a custom-designed next-generation sequencing panel covering 27 genes known to harbor mutations that can cause different types of dementia, in addition to the detection of C9orf72 repeat expansions. Forty-nine patients (19.9%) carried known pathogenic or novel, likely pathogenic, variants, involving both common (presenilin 1, presenilin 2, C9orf72, and granulin) and rare (optineurin, serpin family I member 1 and protein kinase cyclic adenosine monophosphate (cAMP)-dependent type I regulatory subunit beta) dementia-associated genes. Our results support the use of an extended next-generation sequencing panels as a quick, accurate, and cost-effective method for diagnosis in clinical practice. This approach could have a significant impact on the proportion of tested patients, especially among those with an early disease onset.

[Health profile of a population as a predictor of health resources utilization: results of the implementation of an epidemiologic model for needs analysis]. / Profilo di salute di una popolazione come predittore dell'utilizzo di risorse sanitarie: risultati dell'applicazione di un modello epidemiologico per l'analisi dei bisogni.

The integration of the scientific researches in the assistance process is one of the most important challenges that is currently set to the health operators. In this paper a model for the health needs-assessment will be applied to verify if and how the prevalence of some classical risk factors for cardiovascular disease foretells mortality and hospitalisation episodes at 3 years, and if it could express the health need of that population. The "sanitary history" of 1704 subjects, enrolled in 1996 during the Brisighella Study, has been followed. We know the health profile of these subjects at 1996 and data about their hospitalizations, mortality, and general assistance from 1996 to 1999. In this population the risk of cardiovascular disease is inferior to that esteemed by the hospitalisation rate, attributable mostly to a little group of subjects with well-defined characteristics of exposure. The resources spent on a hospitalization do not adequately describe either the sanitary need nor the relief load and the "cost" associated to the disease. The methodology used allows to explore in detail the relative weight of the different subjects involved in the sanitary assistance in order to better reach the objective of producing the maximum quantity of benefits for the patient at the smallest possible quantity of risk.

Serum lipopotein (a) levels in a large sample of subjects affected by familial combined hyperlipoproteinaemia and in general population.

BACKGROUND: Serum lipoprotein (a) [Lp(a)] is a lipidic parameter, strictly under genetic control. Lp(a) levels vary in different dyslipidaemias according to the underlying disease. DESIGN: The aim of this study was to evaluate and compare serum Lp(a) mean levels distribution in a large familial combined hyperlipoproteinaemia (FCH) patients sample with a normolipidaemic group. METHODS: FCH group included 138 subjects (74 males and 65 females) aged from 16 to 88 years; the control group included 438 normolipidaemic subjects (238 males and 200 females) aged from 16 to 91 years. In both groups we have measured Lp(a) concentrations and other lipidic parameters. RESULTS: Serum lipid levels as well as Lp(a) log-transformed concentrations were on average higher in FCH patients than in control subjects. Lp(a) concentrations were not significantly different between sexes and among 20-year age classes in both groups. CONCLUSIONS: The relationship between FCH and Lp(a) remains controversial. However, since both are considered independent risk factors for premature CHD development, even if their pathogenic interaction is still unclear, we suggest that Lp(a) values should be carefully monitored in dyslipidaemic subjects and particularly in FCH ones. In FCH subjects with elevated Lp(a) levels, aggressive intervention could be required.