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.

Lithium Receipt and Risk of Dementia in Older Veterans With Bipolar Disorder in the VA Health System

Older adults with bipolar disorder are at increased risk of developing dementia. The literature suggests lithium treatment may reduce the incidence of dementia. This study sought to inform clinical practice in the Veterans Affairs (VA) health system by estimating the effect of past year lithium receipt on dementia incidence among Veterans with bipolar disorder. Divalproex receipt was used as a comparison. Using VA medical records, 121,094 Veterans aged 50 and older with a diagnosis of bipolar disorder but no dementia diagnosis were identified in fiscal years 2005-2019. Follow-up continued until dementia diagnosis, 36 months from the index date, death, or the end of fiscal year 2020, whichever came first. 4347 (3.6%) were diagnosed with dementia during follow-up. Time-varying indicators of receipt of lithium and divalproex in the prior 365 days were calculated for each day, categorized as 301-365, 61-300, 1-60, or 0 days of receipt. Unadjusted Cox proportional hazards regression analyses indicated reduced dementia incidence with 301-365 (HR=0.86, 95% Confidence Interval [95%CI] 0.75-0.99) and 61-300 (HR=0.75, 95%CI 0.65-0.87) days of lithium receipt, compared to 0 days. For divalproex, 301-365 (HR=1.34, 95%CI 1.23-1.47) and 61-300 (HR=1.13, 95%CI 1.03-1.23) days of receipt were each associated with increased dementia incidence. Lithium effects were not statistically significant after adjusting for age, sex, race, ethnicity, medical comorbidities, and antidepressant, antipsychotic, and anxiolytic medication receipt. Divalproex effects remained statistically significant. Past year divalproex, but not lithium, receipt was significantly associated with dementia incidence among VA patients with bipolar disorder when adjusting for demographics and medical comorbidities.

Estimating Dementia from Self-Reports of Diagnoses Among Adults Aged 65 and Over: United States, 2019

Prior research shows that, overall, about 10% of the population aged 65 and over in the U.S. has dementia. Estimating the prevalence of dementia from nationally representative surveys can be accomplished by asking respondents about a diagnosis, by administering a cognitive assessment, or, if available, by examining linked medical claims data. In 2019 for the first time, the National Health Interview Survey (NHIS) added “dementia, including Alzheimer’s disease” to the questions asking about doctor-diagnosed health conditions. Although estimates derived from doctor-diagnosed questions usually underestimate the true prevalence of a condition, and estimating dementia from self-reports presents additional challenges, they are still useful for many surveillance and research objectives. Early diagnosis of dementia is encouraged to allow patients and their families to plan for future needs. The objective of this research is to describe the noninstitutionalized population aged 65 and over who have a dementia diagnosis, by selected socio-demographic, health, and healthcare utilization characteristics. Point estimates, standard errors, and 95% confidence intervals for percentages are calculated using NHIS adult sample weights and adjusted for the complex sample design of NHIS. Preliminary analyses show that, overall, 4% of the 65 and over noninstitutionalized population has a diagnosis of dementia. About 8% of respondents with less than a high school education reported a dementia diagnosis compared with 2% of those with more than a high school education. Those with a dementia diagnosis were more likely to report depression than those without a dementia diagnosis (44% vs. 14%).

Individuals’ Decision to Disclose a Diagnosis of Dementia and the Development of an Online Empowerment Intervention

Learning to live with a diagnosis of dementia is a complex process. Many people affected by dementia choose not to disclose the diagnosis to others and avoid social activities due to fear of others’ adverse reactions. This in turn can limit their social participation and negatively affect their psychosocial health. A systematic review explored factors influencing the decision to disclose or conceal a dementia diagnosis to one’s social network, including individuals’ attitudes and experiences regarding this decision. The sixteen studies included reveal the complexity of this decision. Findings highlight the role of stigma and individuals’ wishes to remain ‘normal’, but also the need of explaining what has changed. Results were further discussed with people with dementia and informal caregivers as part of patient and public involvement. End users expressed their attitudes, needs, and wishes towards the design of an online empowerment intervention supporting disclosure decision-making in people affected by dementia.