A Novel Heterozygous Missense Variant in the CIAO1 Gene in a Family with Alzheimer’s Disease: The Val67Ile Variant Promotes the Interaction of CIAO1 and Amyloid-β Protein Precursor

Familial dementia is a rare inherited disease involving progressive impairment of memory, thinking, and behavior. We report a novel heterozygous pathogenic variant (c.199G > A, p.Val67Ile) in the CIAO1 gene that appears to be co-segregated with Alzheimer’s disease in a Japanese family. Biochemical analysis of CIAO1 protein revealed that the variant increases the interaction of CIAO1 with immature amyloid-β protein precursor (AβPP), but not mature or soluble AβPP, indicating plausible CIAO1 involvement in AβPP processing. Our study indicates that a heterozygous variant in the CIAO1 gene may be closely related to autosomal dominant familial dementia.

Abstract 074: Familial Dementia Versus Healthy Lifestyle On The Risk Of Dementia

Introduction: Familial dementia (FD) is one of the strongest risk factors for dementia. Little is known about the independent and combined associations of having FD and following a healthy lifestyle with the risk of dementia. Hypothesis: We hypothesized that FD and a healthy lifestyle would be independently associated with the risk of dementia and that a healthy lifestyle would attenuate the risk of dementia among those with FD. Methods: Participants were 302,239 men and women aged 60±5 years who completed a baseline examination between 2006-2010 as part of the UK Biobank study. Participants with dementia at baseline were excluded. FD was defined as dementia in a first-degree relative (i.e., mother, father, or siblings). For healthy behaviors, participants were given one point for each of the following: not having obesity (body mass index <30 kg/m 2 ); ≥150 min/wk of moderate-to-vigorous physical activity; sleep duration between 6-9 hr; drinking in moderation (>0 to ≤14 or 7 drinks/wk for men or women, respectively); not smoking; and following a healthy diet (e.g., more fruits and vegetables; less processed meats and refined grains). Participants were categorized on whether they had ≤2 (reference), 3, 4, 5, or 6 healthy behaviors. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of incident dementia (according to hospital inpatient records and death registry) by FD and number of healthy behaviors. In a joint analysis, participants were categorized based on reporting FD and following ≥3 behaviors. Models were adjusted for age, sex, race, education, socioeconomic status (Townsend deprivation index), hypertension, hypercholesterolemia, diabetes, and depression, with mutual adjustment for healthy behaviors and FD. Results: During an average follow-up of 8 years, 1698 (0.6%) participants developed dementia. Compared to ≤2 healthy behaviors, the HRs (95% CI) were 0.70 (0.57-0.86), 0.58 (0.48-0.70), 0.58 (0.48-0.70) and 0.49 (0.39-0.60) for 3, 4, 5, or 6 behaviors, respectively, after adjusting for the confounders including FD. Compared to no FD, HR (95% CI) of dementia was 1.72 (1.53-1.93) among those with FD after adjusting for the confounders including healthy behaviors. In the joint analysis, compared to those with “FD and ≤2 healthy behaviors”, the HRs (95% CI) for dementia were 0.65 (0.42-0.99), 0.74 (0.47-1.15), and 0.37 (0.25-0.56) for those with “FD and ≥3 behaviors”, “no FD and ≤2 behaviors”, and “no FD and ≥3 behaviors”, respectively. Conclusions: Adopting more healthy behaviors was associated with reduced risk of dementia, independent of FD. In those with FD, adopting at least 3 healthy behaviors may help reduce the risk of developing dementia.

A Novel ITM2B Mutation Associated with Familial Chinese Dementia

Mutations in ITM2B have been found to be associated with familial Danish dementia (FDD) and familial British dementia (FBD). Here, we describe a patient with dementia caused by a novel ITM2B p. *267Leuext *11 mutation. The patient presented with dementia, ataxia, deafness, and paraplegia. Amyloid PET and Tau PET showed abnormal deposition of amyloid and tau protein in brain. Summarized from previous 26 FBD and FDD cases, the clinical phenotype of ITM2B; p. *267Leuext *11 mutation in ITM2B is different from the features of FBD and FDD. Our findings increased genetic knowledge of familial dementia and extend the ethnic distribution of ITM2B mutations.

Exemplary Care among Chinese Dementia Familial Caregivers

Objective: This study investigates the feasibility of using the Exemplary Care Scale (ECS) among Chinese dementia familial caregivers, and reports its psychometric properties. Method: Back translation was used to develop the Chinese version of ECS (C-ECS). Three hundred and ninety-seven dyads of caregivers and their relatives with dementia responded to an assessment battery which included questions on care recipients’ cognition, behavioral and psychological symptoms, daily activities assistance, social support, and caregiver well-being. Results: Results of an exploratory principal component analysis revealed two subscales in the 11-item C-ECS: considerate caregiving and preserving esteem. C-ECS and its subscales demonstrated sufficient reliability, as well as criteria-related validity through its association with care recipient’s cognition and health, and caregivers’ well-being and social support. Discussion: Our findings provide preliminary support to C-ECS as a reliable and valid measure of exemplary caregiving among Hong Kong Chinese familial dementia caregivers. In the light of the increasing importance of familial care in dementia care planning, we recommend the use of this brief scale in regular caregiver assessment in research and service delivery.