JOINT CONTRIBUTION OF MARKERS OF NEURODEGENERATION AND HYPERCHOLESTEROLEMIA TO DEMENTIA RISK

Background The examination of markers of neurodegeneration (glial fibrillary acidic protein; GFAP, neurofilament light chain; NfL, phosphorylated tau181; p-tau181) among individuals with high comorbidity of neurodegenerative and cerebrovascular disease and their interplay with vascular risk factors, particularly high cholesterol levels, might contribute to explaining the link between body and brain. The aim of this study was to assess whether the association of GFAP, NfL, and p-tau181 with dementia risk varies depending on levels of total cholesterol (TC) and APOE ε4 genotype. Methods Nested case-control study embedded within a population-based cohort and including 768 older adults (261 dementia cases and 508 randomly selected controls) followed for up to 17 years with regard to clinical diagnosis of various age-related diseases. GFAP, NfL, and p-tau181 were measured in baseline blood samples using the Single-Molecule Array (Simoa) Technology (Quanterix, USA) and categorized into high (quartile 4) versus low (quartiles 1-3). Logistic regression analyses and spline regression models for dose-response analyses were used. ROC curves by cholesterol levels were also calculated. Results The risk of a dementia diagnosis was significantly increased between participants with high vs. low levels of GFAP and NfL and the risk substantially varied by TC levels. For GFAP and NfL the ORs of a dementia diagnosis were 5.10 (2.45-10.60) and 2.96 (1.43-6.14) in participants with high and 2.44 (1.47-4.07) and 1.15 (0.69-1.92) in those with low TC. APOE ε4 genotype further modified the strength of the associations with different patterns, depending on specific marker and type of dementia. No significant association was seen with p-tau181. Conclusions These results suggest that in the general population blood GFAP and NfL are better predictors of dementia than p-tau181 and that their associations with dementia risk are highly amplified by hypercholesterolemia, also depending on APOE ε4 genotype.

Inter-rater variability in scoring of Addenbrooke’s Cognitive Examination – third edition (ACE-III)

Background: Despite its wide use in dementia diagnosis on the basis of cut-off points, the inter-rater variability of the ACE-III has been poorly studied.Methods: 31 healthcare professionals from an older adults’ mental health team scored two ACE-III protocols based on mock patients in a computerised form. Scoring accuracy, as well as total and domain-specific scoring variability, were calculated; factors relevant to participants were obtained, including their level of experience and self-rated confidence administering the ACE-III.Results: There was considerable inter-rater variability (up to 18 points for one of the cases), and one case’s mean score was significantly higher (by four points) than the true score. The Fluency, Visuospatial and Attention domains had greater levels of variability than Language and Memory. Higher levels of scoring accuracy were not associated with either greater levels of experience not higher self-confidence in administering the ACE-III.Conclusions: The results suggest that the ACE-III is susceptible to scoring error and considerable inter-rater variability, which highlights the critical importance of initial, and continued, administration and scoring training.

The Experiences of Family Caregivers in Response to a Dementia Diagnosis Disclosure

Background: Dementia is a serious disease that can lead to disability because it impacts the individual’s memory, cognition, behavior, and capacity to perform activities of daily living. While most people prefer to receive a full diagnostic disclosure, the actual care requirements of family caregivers, based on their perspectives, are often unknown. The primary aim of this study was to explore the experiences of family caregivers in response to a dementia diagnosis disclosure and analyze the care needs of caregivers.Methods: A qualitative study conducted in accordance with COREQ guidelines. The grounded theory approach was undertaken in 20 family caregivers of patients with dementia, who were selected using purposive sampling. Data were analysed using the constant comparative method.Results: Diagnostic disclosure: Start the long road of care challenges was identified as the core category of this study, which was defined as describing the experiences of family caregivers of patients with dementia after first being informed of the patients’ diagnosis, which activates their willpower to progress against the disease. Five major categories describing the experiences of family caregivers following a dementia diagnosis was developed: ‘deciding to seek medical attention,’ ‘the moment of disclosure,’ ‘conveying information,’ ‘maintaining the patients’ functioning,’ and ‘receiving support and living well with dementia.’ Subcategories within each major category also emerged.Conclusions: Clear diagnostic disclosure is important for ensuring that positive developments can occur in response to disclosure. Healthcare professionals must develop strategies to prevent disclosure from triggering overreactive emotions from patients with cognitive impairments, assist them in understanding their illness in a tactful manner, and ensure that they understand how to cooperate in any subsequent care plans.

Liver Health and Dementia in an Italian Older Population: Findings From the Salus in Apulia Study

Objectives: Non-alcoholic fatty liver disease (NAFLD) currently affects a quarter of the global population. Systemic inflammation, metabolic syndrome, and coronary artery disease, all conditions associated with NAFLD, have also been related to cognitive dysfunction in older age. The present study aimed to investigate the relationship between NAFLD risk and a dementia diagnosis in a large population-based sample aged > 65 years.Methods: We selected 1,542 participants (723 men) from the Salus in Apulia Study. To assess the risk of fat distribution in the liver, we used the Fatty Liver Index (FLI). Dementia was diagnosed according to the American Psychiatric Association criteria (DSM-5).Results: The overall prevalence of dementia was 8.5% [95% confidence interval (CI): 7–10%]. Subjects with dementia were older [effect size (ES): −0.89, 95% CI: −1.07 to −0.70], had a lower level of education (ES:0.88, 95% CI:0.69–1.06), higher levels of gamma-glutamyl transferase (ES: −0.21, 95% CI: −0.39 to −0.03), lower levels of total cholesterol (ES: −0.24, 95% CI: −0.42 to −0.06) and low-density lipoprotein cholesterol (ES: −0.20, 95% CI: −0.38 to 0.02), and a higher FLI (ES: −0.22, 95% CI: −0.39 to −0.04). In the logistic regression model adjusted for age, sex, education, hypertension, diabetes mellitus, alcohol consumption, smoking habits, stroke, cholesterol, and Apo-E, a dementia diagnosis was positively associated with FLI > 60 [odds ratio (OR):1.81; standard error (SE): 0.53; 95% CI: 1.02–3.21].Conclusion: Our findings suggested that an increased NAFLD risk may be associated to dementia and cognitive decline in older age. Considering the high NAFLD prevalence, the possible adverse disease effects on cognitive performance pose a health problem with significant social and economic implications.

Links of Short Physical Performance Battery Score with Incident Dementia: Results from the NHATS

Physical performance is associated with cognitive function in later life, but few studies have examined the prospective association of physical performance with incident dementia. We studied 4539 community-dwelling National Health and Aging Trends Study (NHATS) participants aged ≥65 years with data on demographics and the Short Physical Performance Battery (SPPB) in 2011, who were followed through 2014. Our outcome was dementia diagnosis from a validated NHATS algorithm. We applied survey weights to make results nationally representative and performed Cox regression analyses. After adjustment for potential confounders, lower baseline SPPB scores were associated with incident dementia (HR=1.68, p < 0.01). Slower gait speed was the SPPB component most strongly associated with incident dementia (HR=1.21, p < 0.01). We found that poorer physical performance was linked to incident dementia in a cohort of older adults. More research is needed to examine the effect of improving physical performance on the prevention of dementia.