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Background: The utility of Polygenic Risk Scores (PRS) is gaining increasing attention for generating an individual genetic risk profile to predict subsequent likelihood of future onset of Alzheimer's disease (AD), especially those carry two copies of the APOE E3 allele, currently considered at neutral risk in all populations studied.

Objectives: To access the performance of PRS in predicting individuals whilst pre-symptomatic or with mild cognitive impairment who are at greatest risk of progression of cognitive impairment due to Alzheimer's Disease from the Alzheimer's Disease Neuroimaging Initiative (ADNI) as measured by the Preclinical Alzheimer Cognitive Composite (PACC) score profile. Design: A longitudinal analysis of data from the ADNI study conducted across over 50 sites in the US and Canada.

Setting: Multi-centre genetics study.

Participants: 594 subjects either APOE E3 homozygotes or APOE E3/E4 heterozygotes who upon entry to the study were diagnosed as cognitively normal or with mild cognitive impairment.

Measurements: Use of genotyping and/or whole genome sequencing data to calculate polygenic risk scores and assess its ability to predict subsequent cognitive decline as measured by PACC over 5 years. Results: Assessing both cognitively normal and mild cognitive impaired subjects using a PRS threshold of greater than 0.6, the high genetic risk participant group declined more than the low risk group over 5 years as measured by PACC score (PACC score reduced by time).

Conclusions: Our findings have shown that polygenic risk score provides a promising tool to identify those with higher risk to decline over 5 years regardless of their APOE alleles according to modified PACC profile, especially its ability to identify APOE3/E3 cognitively normal individuals who are at most risk for early cognitive decline. This genotype accounts for approximately 60% of the general population and 35% of the AD population but currently would not be considered at higher risk without access to expensive or invasive biomarker testing.

Objective: The purpose of this longitudinal, observational study was to examine whether age and seasonal changes in sedentary activity (sedAct), moderate-to-vigorous physical activity (MVPA), and energy intake (EI) predict changes in body composition among midlife women. We hypothesized that reductions in MVPA and increases in sedAct and EI in winter, along with greater baseline age would predict increases in percentage body fat (%BF) across seasons.

Design: This study used a longitudinal, within-subjects design. Setting: This study took place in Grand Forks, North Dakota.

Participants: Participants included 52 midlife women (aged 40-60 years) who were observed over the course of one year.

Measurements: Percentage body fat measures were obtained via whole body Dual Energy X-ray absorptiometry. Participants were scanned once per season. We measured EI using the ASA24®. We used a GTX3 accelerometer to measure physical activity. Each season, participants wore the monitors for 7 days, 12 hours per day. All measures began in summer.

Results: Results of hierarchical multiple regression (MR) analyses showed that age increases (β = 0.310, p = 0.021) and summer-to-fall increases in EI (β = 0.427, p = 0.002) predicted seasonal increases in %BF (R2 = .36, F(5, 42)= 4.66, p = 0.02). Changes in MVPA and sedAct were not significant predictors. Repeated measures ANCOVA revealed that summer (M = 37.7263, 95% CI [35.8377, 39.6149]) to winter (M = 38.1463, 95% CI [36.1983, 40.0942]) increases in %BF are not reversed by spring (M = 37.8761, 95% CI [35.9365, 39.8157]).

Conclusions: To minimize increases in %BF and maintain health, midlife women, particularly older women, should be encouraged to pay extra attention to their diet in the fall months.

Background: Recent advances open the opportunity of altering the course of Alzheimer's disease (AD) through lifestyle-based modifications and novel therapies. Ensuring that society is investing limited budgets in the interventions that have the greatest potential to generate tangible impact will require tools to guide policymakers.

Objectives: To build on previous studies to develop an economic model that estimates the societal burden of AD and evaluates the potential impact of novel interventions in six large European countries.

Design: AD progression was modelled using a published Markov structure with a 40-year time horizon to estimate lifetime costs and life years in a cohort aged 65 years and above diagnosed with mild cognitive impairment due to AD (MCI-AD) in 2020. Demographic projections were utilized to estimate the prevalence of MCI-AD up to 2100, total corresponding costs and life years. The model allows a comparison of costs associated with the introduction of a hypothetical new disease-modifying therapy that slows disease progression between MCI-AD and all AD-Dementia stages as well as a 'delayed onset' scenario where disease progression is halted at the MCI-AD stage, potentially occurring, for example, through lifestyle-based modifications.

Results: The 2022 present value of total lifetime costs for this cohort moving through all disease stages is ~€1.2T. Approximately 80% of the present value of lifetime costs in our model are driven by informal care and non-medical direct costs. Our model suggests that a 25% and 50% reduction in disease progression compared to natural history could translate into a present value of cost savings of €33.7B and €72.7B. Halting MCI-AD progression for 3 years with no therapeutic effect thereafter resulted in a present value cost savings of €84.7B in savings.

Conclusions: Our data further suggest that early intervention via disease-modifying therapies or lifestyle-based modifications in AD could result in cost savings for society. Additionally, our findings reinforce the importance of accounting for the full value of innovative interventions, management and care paradigms, including their potential impact on direct, indirect and intangible costs impacting patients, their care partners and health and social care systems.

Background: It is inconclusive on how apolipoprotein epsilon (APOE) gene polymorphism is associated with the risk of having mild cognitive impairment (MCI) or Alzheimer's disease (AD).

Objectives: To investigate how APOE genotype is associated with the risk of MCI or AD using the data collected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) participants.

Methods: A cross-sectional design was used to analyze the baseline data collected from the 1,720 ADNI participants. APOE gene polymorphism was analyzed on how they are related to the risk of cognitive impairments of either MCI or AD using a percent yield (PY) method. Then cognitive functions were compared among six different APOE genotypes using a two-way ANCOVA by controlling possible confounding factors.

Results: The prevalence of six APOE genotypes in 1,720 participants is as following: e2/e2 (0.3%), e2/e3 (7.4%), e3/e3 (45.4%), e2/e4 (2%), e3/e4 (35%) and e4/e4 (9.9%). The e2/e2 and e4/e4 genotypes were associated with the lowest and the highest risk respectively for cognitive impairments of either MCI or AD. Further, a worse cognitive diagnosis was associated with an increasing number of APOE e4 allele in a dose dependent manner. Participants with genotype e3/e3 had a better memory measure than those with the genotype of e3/e4.

Conclusions: APOE gene polymorphism is associated with different level of risks for cognitive impairments. The heterozygous genotype e3/e4 is associated with a worse memory function compared to the genotype of e3/e3. Further investigations are needed to intervene the cognitive deteriorations in those with at risk APOE genotypes.

Background: Preventing frailty is important to avoid adverse health outcomes. Intervention studies have largely focused on frail elderly, although the intermediate pre-frail state may be more amenable to improvement.

Objectives: This study aims to assess how physical performance may change among pre-frail elderly enrolled in a pragmatic non-controlled exercise and nutritional intervention programme.

Methods: This is a non-controlled study involving a 4-month exercise and nutritional intervention for community dwelling pre-frail older adults. Pre-frailty was defined as the presence of 1 or 2 positive responses on the FRAIL questionnaire, or evidence of weak grip strength (<26kg for males; <18kg for females) or slow gait speed (<0.8m/s) amongst participants who were asymptomatic on FRAIL. Physical performance in flexibility, grip and lower limb strength, endurance, balance, and Short Physical Performance Battery were measured at 3 time-points: baseline, 3-month from recruitment (without intervention), and immediate post-intervention. Repeated measures mixed model analysis was performed to compare physical performance measures across the 3 time-points.

Results: 94 pre-frail participants were eligible for intervention, of whom 59 (mean age = 70.9±7.2 years) were ready for the post-intervention review. 21 (35.6%) transitioned to robust phenotype while 32 (54.2%) remained as pre-frail. Significant improvement post-intervention was observed in lower limb strength and power, evident on reduction in time taken for 5 sit-to-stand repetitions (0.46±0.20s, p=0.03). There was no significant change to the other physical performance measures examined.

Conclusion: We observed reversibility of pre-frailty, and the benefit of multi-component intervention in improving physical performance of pre-frail older adults. The findings in this non-controlled study will need to be corroborated with future controlled trials.

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.

The lockdown restrictions imposed as a result of COVID-19 impacted on many areas of daily life including dietary behaviours. A cohort of middle-older age adults (n=17), who had previously provided 3-day food diaries in May 2019 were asked to record their 3 day dietary intake in May 2020 when the UK was under lockdown restrictions. Mean (SD) energy intakes were significantly higher by ~750kilojoules in 2020 (8587kJ (1466.9)) compared to 2019 (7837 kJ (1388.9)). This energy increase is equivalent to ~170kcal; approximately 2 slices of bread. Furthermore, recorded meat/meat products, riboflavin, vitamin B6/B12 and iron intakes were all greater in 2020. No other dietary differences were observed between the two timepoints. This was a small, homogenous but well controlled sample, who exhibited a relatively stable diet during lockdown compared with pre-pandemic intakes 12 months earlier. It can be concluded that there was little evidence of food insecurity in this cohort.

Purpose: Low skeletal muscle mass determined radiographically has emerged as an important prognostic marker in penile cancer patients but may be unrecognized in obese patients with a high comorbid disease burden. Moreover, publicly available software for image segmentation are limited. Thus, we describe the prevalence of radiographically low skeletal muscle mass in an obese penile cancer cohort, using an open-source software and examine its association with comorbid disease burden.

Methods: This is a cross-sectional study, utilizing retrospective data from patients diagnosed with penile squamous cell carcinoma between October 2009 and December 2019. Available digital files of perioperative computerized tomography were analyzed, using CoreSlicer, an open-source image segmentation software. The correlation between radiographically low skeletal muscle mass, defined as a skeletal muscle index (SMI) less than 55 cm2/m2 and a Charlson Comorbidity Index (CCI) greater than 4 was examined, using logistic and linear regression.

Results: Forty two of 59 patients had available digital files. Median SMI and body mass index (BMI) were 54.6cm2/m2 and 30.2kg/m2 respectively for the entire cohort. Of included patients, 54% had radiographically low skeletal muscle mass and a median BMI of 28.9 kg/m2. Radiographically low skeletal muscle mass was associated with a CCI greater than 4 on univariable and multivariable logistic regression with odds ratios of 4.85 (p = 0.041) and 7.32 (p = 0.033), respectively. When CCI was treated as a continuous variable on linear regression, the association between radiographically low skeletal muscle mass and CCI was positive, but not statistically significant with an estimated effect of 1.29 (p = 0.1) and 1.27 (p = 0.152) on univariable and multivariable analysis, respectively.

Conclusion: Our data demonstrate that low skeletal muscle mass can be readily assessed with CoreSlicer and is associated with a CCI greater than 4 in obese penile cancer patients.