Risk Of Future Dementia Research Articles

Semantic fluency deficits and associated brain activity in Parkinson’s disease with mild cognitive impairment

People living with Parkinson’s disease (PD) with poor verbal fluency have an increased risk of developing dementia. This study examines the neural mechanisms underpinning semantic fluency deficits in patients with PD with mild cognitive impairment (PD-MCI) compared to those without MCI (PD-NC) and control participants without PD (non-PD). Thirty-seven (37) participants with PD completed a cognitive assessment battery to identify MCI (13 PD-MCI). Twenty sex- and age-matched non-PD patients also participated. Participants were scanned (3T Siemens PRISMA) while performing semantic fluency, semantic switching, and automatic speech tasks. The number of responses and fMRI data for semantic generation and semantic switching were analyzed. Participants also completed a series of verbal fluency tests outside the scanner, including letter fluency. Participants with PD-MCI performed significantly worse than PD-NC and non-PD participants during semantic fluency and semantic switching tasks. PD-MCI patients showed greater activity in the right angular gyrus than PD-NC and non-PD patients during semantic switching. Increased right angular activity correlated with worse verbal fluency performance outside the scanner. Our study showed that the PD-MCI group performed worse on semantic fluency than either the PD-NC or non-PD groups. Increased right angular gyrus activity in participants with PD-MCI during semantic switching suggests early compensatory mechanisms, predicting the risk of future dementia in PD.

Reduced cerebral vascular fractal dimension among asymptomatic individuals as a potential biomarker for cerebral small vessel disease

Cerebral small vessel disease is a neurological disease frequently found in the elderly and detected on neuroimaging, often as an incidental finding. White matter hyperintensity is one of the most commonly reported neuroimaging markers of CSVD and is linked with an increased risk of future stroke and vascular dementia. Recent attention has focused on the search of CSVD biomarkers. The objective of this study is to explore the potential of fractal dimension as a vascular neuroimaging marker in asymptomatic CSVD with low WMH burden. Df is an index that measures the complexity of a self-similar and irregular structure such as circle of Willis and its tributaries. This exploratory cross-sectional study involved 22 neurologically asymptomatic adult subjects (42 ± 12 years old; 68% female) with low to moderate 10-year cardiovascular disease risk prediction score (QRISK2 score) who underwent magnetic resonance imaging/angiography (MRI/MRA) brain scan. Based on the MRI findings, subjects were divided into two groups: subjects with low WMH burden and no WMH burden, (WMH+; n = 8) and (WMH−; n = 14) respectively. Maximum intensity projection image was constructed from the 3D time-of-flight (TOF) MRA. The complexity of the CoW and its tributaries observed in the MIP image was characterised using Df. The Df of the CoW and its tributaries, i.e., Df (w) was significantly lower in the WMH+ group (1.5172 ± 0.0248) as compared to WMH− (1.5653 ± 0.0304, p = 0.001). There was a significant inverse relationship between the QRISK2 risk score and Df (w), (rs = − .656, p = 0.001). Df (w) is a promising, non-invasive vascular neuroimaging marker for asymptomatic CSVD with WMH. Further study with multi-centre and long-term follow-up is warranted to explore its potential as a biomarker in CSVD and correlation with clinical sequalae of CSVD.

Longitudinal Association Between Oral Status and Cognitive Decline Using Fixed-effects Analysis.

BackgroundAlthough the feasibility of randomized trials for investigating the long-term association between oral health and cognitive decline is low, deriving causal inferences from observational data is challenging. We aimed to investigate the association between poor oral status and subjective cognitive complaints (SCC) using fixed-effects model to eliminate the confounding effect of unobserved time-invariant factors.MethodsWe used data from Japan Gerontological Evaluation Study (JAGES) which was conducted in 2010, 2013, and 2016. β regression coefficients and 95% confidence intervals [CIs] were calculated using fixed-effects models to determine the effect of deteriorating oral status on developing SCC. Onset of SCC was evaluated using the Kihon Checklist-Cognitive function score. Four oral status variables were used: awareness of swallowing difficulty, decline in masticatory function, dry mouth, and number of teeth.ResultsWe included 13,594 participants (55.8% women) without SCC at baseline. The mean age was 72.4 (standard deviation [SD], 5.1) years for men and 72.4 (SD, 4.9) years for women. Within the 6-year follow-up, 26.6% of men and 24.9% of women developed SCC. The probability of developing SCC was significantly higher when participants acquired swallowing difficulty (β = 0.088; 95% CI, 0.065–0.111 for men and β = 0.077; 95% CI, 0.057–0.097 for women), decline in masticatory function (β = 0.039; 95% CI, 0.021–0.057 for men and β = 0.030; 95% CI, 0.013–0.046 for women), dry mouth (β = 0.026; 95% CI, 0.005–0.048 for men and β = 0.064; 95% CI, 0.045–0.083 for women), and tooth loss (β = 0.043; 95% CI, 0.001–0.085 for men and β = 0.058; 95% CI, 0.015–0.102 for women).ConclusionThe findings suggest that good oral health needs to be maintained to prevent the development of SCC, which increases the risk for future dementia.

Trajectories of cognitive decline and dementia development: A 12-year longitudinal study.

Mapping the preclinical dementia phase is important for early detection and evaluation of interventions. We assessed the trajectories of cognitive decline in preclinical dementia over 12 years and investigated whether being a fast decliner across 6 years is associated with increased risk of dementia the following 6 years. Rates of cognitive decline were determined using mixed-effects models for 1646 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) cohort. Cox regression was used to assess the future likelihood of dementia for fast decliners (declining ≥1.5 standard deviations [SDs] faster than the age-specific rates). Participants in a preclinical phase of dementia showed increased rates of decline in all cognitive tests compared to the no-dementia group, particularly closer (0-6 years) to diagnosis. Participants declining fast in three or more cognitive tests 12-6 years before diagnosis demonstrated a high risk of dementia 6 years later (hazard ratio [HR] 3.90, 95% confidence interval [CI] 2.28-6.69). Being a fast decliner is linked to increased risk of future dementia.

Social Isolation Is Associated with Future Dementia Risk, New Analysis Finds

Social Isolation Is Associated with Future Dementia Risk, New Analysis Finds

Neuroimaging and cognitive correlates of retinal Optical Coherence Tomography (OCT) measures at late middle age in a twin sample

Sharing in embryology and function between the eye and brain has led to interest in whether assessments of the eye reflect brain changes seen in neurodegeneration. We aimed to examine the associations between measures of retinal layer thickness using optical coherence tomography (OCT) and multimodal measures of brain structure and function. Using a convenient sample of twins discordant for type 2 diabetes, we performed cognitive testing, structural brain MRI (tissue volumetry), diffusion tensor imaging (white matter microstructure), and arterial spin labelling (cerebral blood flow). OCT images were recorded and retinal thickness maps generated. We used mixed level modelling to examine the relationship between retinal layer thicknesses and brain measures. We enrolled 35 people (18 pairs, mean age 63.8 years, 63% female). Ganglion cell layer thickness was positively associated with memory, speed, gray matter volume, and altered mean diffusivity. Ganglion cell layer thickness was strongly positively associated with regional cerebral blood flow. We found only a limited number of associations between other retinal layer thickness and measures of brain structure or function. Ganglion cell layer thickness showed consistent associations with a range of brain measures suggesting it may have utility as a marker for future dementia risk.

142-LB: Cognitive Screening among Older Adults with Diabetes

Background: Diabetes affects approximately 24.4% of older adults in the United States and increases the risk of cognitive dysfunction and future dementia. Patients with cognitive dysfunction may find it harder to manage their diabetes and have more complications such as hypoglycemia. Yearly cognitive screening is recommended for all older adults with diabetes but may not be widely conducted. Methods: We performed cognitive screening with the Mini-Cog test for a subset of patients with diabetes seen in Endocrine Clinics in one large healthcare system in 2020-21. We used a retrospective chart review to compare patient screening results between Endocrine (Endo) , Geriatric (Geri) and multidisciplinary Endo-Geriatric practices (Geri-Endo) . We used Chi-square tests to examine differences between clinic cohorts and a multivariate logistic regression to predict risk of cognitive dysfunction. We adjusted for age, ethnicity, sex, type of diabetes, Sulfonylurea (SU) use, ACE inhibitors (ACEI) / Angiotensin Receptor Blocker (ARB) use, smoking history, statin use, and BMI. Findings: Among 198 patients screened (Endo=80, Geri=32, Geri-Endo=86) , those seen in Geri-endo (40.7%) and Geri (31.3%) were more likely to have lower Mini-COG scores (lower scores suggest worse cognition) as compared to those in Endo (6.3%) (p<.0001) . Patients in Endo and Geri-Endo had longer duration of diabetes, were more likely to use insulin and had higher incidence of documented hypoglycemia. Higher age > 75 years (p=0.0105) , previous CV events (p=0.0006) and BMI <30 (p=0.0115) were significantly associated with lower Mini-COG scores. Conclusion: Our study shows that cognitive screening can help identify older adults at risk for dementia in diabetes clinic. Patients with older age, previous CV events and lower BMI may be at higher risk for cognitive dysfunction. Older adults should be screened yearly for cognition as part of routine diabetes care. Disclosure D. Gupta: None. H. Wilhalme: None. G. Sauder: None. T. Moin: None. Funding NIH National Center for Advancing Translational Science (NCATS) , UCLA CTSI (UL1TR001881)

Mild Traumatic Brain Injuries and Future Risk of Developing Alzheimer's Disease: Systematic Review and Meta-Analysis.

Traumatic brain injury (TBI) increases the risk of future dementia and Alzheimer's disease (AD). However, it is unclear whether this is true for mild TBI (mTBI). To explore the association between mTBI and subsequent risk of developing AD. We systematically searched four electronic databases from January 1954 to April 2020. We included studies reporting primary data and where mTBI preceded AD by≥5 years. We meta-analyzed included studies for both high quality studies and studies with a follow up of > 10 years. We included 5 of the 10,435 results found. Meta-analysis found a history of mTBI increased risk of AD (pooled relative risk = 1.18, 95% CI 1.11-1.25, N = 3,149,740). The sensitivity analysis including only studies in which mTBI preceded AD by > 10 years, excluded two very large studies and resulted in wider confidence intervals (RR = 2.02, 95% CI 0.66-6.21, N = 2307). There is an increased risk of AD following mTBI. Our findings of increased risk even with mTBI means it cannot be assumed that mild head injuries from sports are harmless. The sensitivity analysis suggests that we cannot exclude reverse causation, and longer follow up times are needed. Implementation of policy to reduce mTBIs, including in children and sportsmen, are urgently needed. Further research is needed on the effect of frequency and age at injury of mTBIs.

Biopsychosocial Correlates of Subjective Cognitive Decline and Related Worry in the Canadian Longitudinal Study on Aging

Introduction: Subjective cognitive decline (SCD), a self-reported decline in cognition in otherwise cognitively healthy people, has been acknowledged as a risk factor for Alzheimer’s disease. Using data from the Canadian Longitudinal Study on Aging (CLSA), a large national study with participants’ ages of 45–85 years at baseline, we sought to identify correlates of SCD and SCD-related worry. Methods: In our primary analysis using a Poisson regression model, associations between biopsychosocial variables and SCD were identified (analytic sample: n = 21,920). In a second analysis using an ordinal regression model, associations between biopsychosocial variables and SCD-related worry were identified (analytic sample: n = 12,694). Results: Multiple risk and protective factors of cognitive decline were not associated with SCD within our sample (i.e., physical activity, hypertension, vision problems), as well as minority stress variables such as sexual orientation and race. Rather, psychosocial variables (i.e., depression, perceived social status, and personality traits) showed a more consistent association with SCD within the sample. Greater SCD-related worry, which is believed to increase the risk of future dementia, was associated with specific personality traits, depression, age, gender, and sexuality. Conclusion: The results from this study confirm the association between multiple health variables and SCD but also emphasize the importance of considering psychological and social factors when conceptualizing SCD and its risk factors.

Metabolites Associated with Memory and Gait: A Systematic Review.

We recently found that dual decline in memory and gait speed was consistently associated with an increased risk of dementia compared to decline in memory or gait only or no decline across six aging cohorts. The mechanisms underlying this relationship are unknown. We hypothesize that individuals who experience dual decline may have specific pathophysiological pathways to dementia which can be indicated by specific metabolomic signatures. Here, we summarize blood-based metabolites that are associated with memory and gait from existing literature and discuss their relevant pathways. A total of 39 eligible studies were included in this systematic review. Metabolites that were associated with memory and gait belonged to five shared classes: sphingolipids, fatty acids, phosphatidylcholines, amino acids, and biogenic amines. The sphingolipid metabolism pathway was found to be enriched in both memory and gait impairments. Existing data may suggest that metabolites from sphingolipids and the sphingolipid metabolism pathway are important for both memory and gait impairments. Future studies using empirical data across multiple cohorts are warranted to identify metabolomic signatures of dual decline in memory and gait and to further understand its relationship with future dementia risk.

Blueberry Supplementation in Midlife for Dementia Risk Reduction.

Late-life dementia typically develops over a period of many years beginning in midlife. Prevalence of metabolic disturbance also accelerates in middle age and is a prominent risk factor for dementia. Preliminary studies indicate that blueberry supplementation can improve cognitive performance and influence metabolism and brain function and therefore may have a role in early intervention to prevent neurodegeneration. In a randomized controlled trial, we investigated the effects of daily blueberry supplementation in a middle-aged sample of insulin-resistant participants with elevated risk for future dementia. We enrolled overweight men and women, aged 50 to 65 years, with subjective cognitive decline (SCD) and performed pre- and post-intervention assessments of cognition and metabolism and exploratory measures of peripheral mitochondrial function. We observed improved performances for the blueberry group on measures of lexical access, p = 0.003, and memory interference, p = 0.04, and blueberry-treated participants reported reduced memory encoding difficulty in daily life activities, p = 0.03. The blueberry-treated group also exhibited correction of peripheral hyperinsulinemia, p = 0.04, and a modest trend for increased mitochondrial uncoupling, p = 0.11. The cognitive findings indicated improved executive ability in this middle-aged sample. In addition, the changes in metabolic and bioenergetic measures imply potential mechanistic factors associated with anthocyanin and proanthocyanidin actions. The demonstration of these benefits in middle-aged individuals with insulin resistance and SCD suggests that ongoing blueberry supplementation may contribute to protection against cognitive decline when implemented early in at-risk individuals.

Higher Dementia Risk in People With Gastroesophageal Reflux Disease: A Real-World Evidence.

BackgroundWhether or not patients with gastroesophageal reflux disease (GERD) have a higher risk of developing subsequent dementia remains unknown, and no observational evidence from population-based data is available. This study was to determine whether patients with GERD have a higher future risk of developing dementia.MethodsFor the period 2000–2012, datasets from the Longitudinal Health Insurance Database (LHID, subset of National Health Insurance Research Database in Taiwan) were analyzed. Definition of GERD was based on ICD-9-CM codes 530.11 and 530.81 and prescriptions for PPIs. After matching gender, age, index year, and comorbidities, each GERD patient was matched with four control patients without GERD. Future risk of dementia was evaluated, and sensitivity analysis of subgroups was conducted to clarify the potential association.ResultsIn the present study, 13,570 patients were included in the GERD cohort and 54,280 patients were included in the control cohort. Patients with GERD showed higher risk developing dementia than control group, with an aHR of 1.34 (95% C.I., 1.07, 1.67). In GERD patients between above 70 years old, the risk of developing dementia was higher than that of the control groups (aHR = 1.34; 95% C.I., 1.01, 1.77).ConclusionPatients with GERD showed higher incidence of dementia, and elder patients had the highest risk of developing dementia. Clinicians should be concern of the association between GERD and dementia and should develop strategies to prevent dementia while managing patients with GERD.

The relationship between isolated hypertension with brain volumes in UK Biobank.

BackgroundHypertension is a well‐established risk factor for cognitive impairment, brain atrophy, and dementia. However, the relationship of other types of hypertensions, such as isolated hypertension on brain health and its comparison to systolic‐diastolic hypertension (where systolic and diastolic measures are high), is still relatively unknown. Due to its increased prevalence, it is important to investigate the impact of isolated hypertension to help understand its potential impact on cognitive decline and future dementia risk. In this study, we compared a variety of global brain measures between participants with isolated hypertension to those with normal blood pressure (BP) or systolic‐diastolic hypertension using the largest cohort of healthy individuals.MethodsUsing the UK Biobank cohort, we carried out a cross‐sectional study using 29,775 participants (mean age 63 years, 53% female) with BP measurements and brain magnetic resonance imaging (MRI) data. We used linear regression models adjusted for multiple confounders to compare a variety of global, subcortical, and white matter brain measures. We compared participants with either isolated systolic or diastolic hypertension with normotensives and then with participants with systolic‐diastolic hypertension.ResultsThe results showed that participants with isolated systolic or diastolic hypertension taking BP medications had smaller gray matter but larger white matter microstructures and macrostructures compared to normotensives. Isolated systolic hypertensives had larger total gray matter and smaller white matter traits when comparing these regions with participants with systolic‐diastolic hypertension.ConclusionsThese results provide support to investigate possible preventative strategies that target isolated hypertension as well as systolic‐diastolic hypertension to maintain brain health and/or reduce dementia risk earlier in life particularly in white matter regions.

Macrostructural brain alterations at midlife are connected to cardiovascular and not inherited risk of future dementia: the PREVENT-Dementia study

BackgroundMacrostructural brain alterations in the form of brain atrophy or cortical thinning typically occur during the prodromal Alzheimer’s disease stage. Mixed findings largely dependent on the age of the examined cohorts have been reported during the preclinical, asymptomatic disease stage. In the present study, our aim was to examine the association of midlife dementia risk with brain macrostructural alterations.MethodsStructural 3T MRI scans were acquired for 647 cognitively normal middle-aged (40–59 years old) participants in the PREVENT-Dementia study. Cortical thickness, volumes of subcortical structures, the hippocampus and hippocampal subfields were quantified using Freesurfer version 7.1. The clarity of the hippocampal molecular layer was evaluated based on T2-weighted hippocampal scans. Associations of structural measures with apolipoprotein ε4 (APOE4) genotype and dementia family history (FHD), were investigated using linear regression. Correlations between the CAIDE dementia risk score (incorporating information about blood pressure, cholesterol, physical activity, body mass index, education, age and sex) and structural measures were further investigated.ResultsA higher CAIDE score was associated with thinner cortex and a larger hippocampal fissure. APOE4 genotype was associated with reduced molecular layer clarity.ConclusionsOur findings suggest that a higher CAIDE score is associated with widespread cortical thinning. Conversely, APOE4 carriers and participants with FHD do not demonstrate prominent macrostructural alterations at this age range. These findings indicate that cardiovascular and not inherited risk factors for dementia are associated with macrostructural brain alterations at midlife.

Abstract MP22: Myosteatosis Is Associated With Worse Cognition In African Caribbean Women

Introduction: Skeletal muscle adipose tissue infiltration (i.e. myosteatosis) increases with aging, and is recognized as a major risk factor for cardio-metabolic diseases. While it is known that visceral adiposity is related to dementia and cognitive decline, the relationship between myosteatosis and cognition is not well understood. Such studies are particularly needed among African ancestry women, who have greater myosteatosis and higher burden of Alzheimer’s Disease and Related Dementias compared with White women. Aim: The objective of this study was to assess if, among African Caribbean middle-aged and older women (aged 40-79), myosteatosis is associated with cognitive function. Methods: Data were collected on women (n=481) from the Tobago Health Study. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a test of information processing speed; DSST is a fast, reliable and sensitive test that predicts onset of dementia. DSST was administered to participants by trained interviewers; scores ranged from 0 to 81 (lower score indicating cognitive decline). Peripheral Quantitative Computed Tomography (Stratec XCT-2000) was used to measure calf skeletal muscle density (MD), which was used as a proxy measure for the myosteatosis (lower MD reflects more adiposity). Linear regression was used to assess the association of muscle density with cognition and was adjusted for age, education, muscle area, waist circumference, alcohol intake, smoking, walking hours, diabetes and hypertension. Results for the primary predictor of interest (MD) were standardized with effects shown per standard deviation (SD). Results: Mean (SD) DSST scores were 38.8 (13.2). Overall, participants were aged 55.2 years and had a BMI of 30.7 kg/m 2 . Mean (SD) MD was 71.7((5.3) (mg/cm 3 ). As expected, in unadjusted analyses, the strongest predictors of lower DSST scores in these women were older age and lower education, higher waist circumference, diabetes and hypertension. After full adjustment, we found that a one SD increase in MD was associated with a 1.48 increase in DSST score (p-value=0.015). Conclusions: Our findings suggest that in African Caribbean women, greater myosteatosis is associated with slower information processing speed, an early indicator of future dementia risk. Future studies using expanded battery of cognitive tests and longitudinal follow-up are warranted to further advance our understanding of the novel role of myosteatosis in dementia risk among African ancestry women.

Metabolomic profiling in small vessel disease identifies multiple associations with disease severity.

Cerebral small vessel disease is a major cause of vascular cognitive impairment and dementia. There are few treatments, largely reflecting limited understanding of the underlying pathophysiology. Metabolomics can be used to identify novel risk factors to better understand pathogenesis and to predict disease progression and severity.We analysed data from 624 patients with symptomatic cerebral small vessel disease from two prospective cohort studies. Serum samples were collected at baseline and patients underwent MRI scans and cognitive testing at regular intervals with up to 14 years of follow-up. Using ultra-performance liquid chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy, we obtained metabolic and lipidomic profiles from 369 annotated metabolites and 54 764 unannotated features and examined their association with respect to disease severity, assessed using MRI small vessel disease markers, cognition and future risk of all-cause dementia.Our analysis identified 28 metabolites that were significantly associated with small vessel disease imaging markers and cognition. Decreased levels of multiple glycerophospholipids and sphingolipids were associated with increased small vessel disease load as evidenced by higher white matter hyperintensity volume, lower mean diffusivity normalized peak height, greater brain atrophy and impaired cognition. Higher levels of creatine, FA(18:2(OH)) and SM(d18:2/24:1) were associated with increased lacune count, higher white matter hyperintensity volume and impaired cognition. Lower baseline levels of carnitines and creatinine were associated with higher annualized change in peak width of skeletonized mean diffusivity, and 25 metabolites, including lipoprotein subclasses, amino acids and xenobiotics, were associated with future dementia incidence.Our results show multiple distinct metabolic signatures that are associated with imaging markers of small vessel disease, cognition and conversion to dementia. Further research should assess causality and the use of metabolomic screening to improve the ability to predict future disease severity and dementia risk in small vessel disease. The metabolomic profiles may also provide novel insights into disease pathogenesis and help identify novel treatment approaches.

Body Mass Index and Mild Cognitive Impairment Among Middle-Aged and Older Adults from Low- and Middle-Income Countries.

The effect of weight modification on future dementia risk is currently a subject of debate and may be modified by age. The aim of the present study was to investigate the association between body mass index (BMI) status with mild cognitive impairment (MCI) (a preclinical stage of dementia) in middle-aged and older adults residing in six low- and middle-income countries using nationally representative data. Cross-sectional data from the Study on Global Ageing and Adult Health (SAGE) were analyzed. MCI was defined using the National Institute on Aging-Alzheimer's Association criteria. BMI (kg/m2) was based on measured weight and height and categorized as: underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0). Multivariable logistic regression analysis and meta-analysis were conducted to assess associations. Data on 32,715 individuals aged ≥50 years with preservation in functional abilities were analyzed [mean (SD) age 62.1 (15.6) years; 51.7% females]. Among those aged 50-64 years, compared to normal weight, underweight (OR = 1.44; 95% CI = 1.14-1.81), overweight (OR = 1.17; 95% CI = 1.002-1.37), and obesity (OR = 1.46; 95% CI = 1.09-1.94) were all significantly associated with higher odds for MCI. In those aged ≥65 years, underweight (OR = 0.71; 95% CI = 0.54-0.95) and overweight (OR = 0.72; 95% CI = 0.55-0.94) were associated with significantly lower odds for MCI, while obesity was not significantly associated with MCI. The results of the study suggest that the association between BMI and MCI is likely moderated by age. Future longitudinal studies are required to confirm or refute the present findings before recommendations for policy and practice can be made.

Weight loss in a cardiovascular trial population identifies people at future risk of dementia.

IntroductionPopulations at increased risk of dementia need to be identified for well‐powered trials of preventive interventions. Weight loss, which often occurs in pre‐clinical dementia, could identify a population at sufficiently high dementia risk.MethodsIn 12,975 survivors in the Heart Protection Study statin trial of people with, or at high risk of, cardiovascular disease, the association of weight change over 5 years during the trial with post‐trial dementia recorded in electronic hospital admission and death records (n = 784) was assessed, after adjustment for age, sex, treatment allocation, and deprivation measures.ResultsAmong the 60% without substantial weight gain (≤2 kg weight gain), each 1 kg weight loss was associated with a risk ratio for dementia of 1.04 (95% confidence interval, 1.02–1.07). Weight loss ≥4 kg and cognitive function below the mean identified participants aged ≥67 years with a 13% 10‐year dementia risk.DiscussionThe combination of weight loss and high vascular risk identified individuals at high risk of dementia who could be recruited to dementia prevention trials.

Apathy and APOE in mild behavioral impairment, and risk for incident dementia.

Mild behavioral impairment (MBI) is a high-risk state for incident dementia and comprises five core domains including affective dysregulation, impulse dyscontrol, social inappropriateness, psychotic symptoms, and apathy. Apathy is among the most common neuropsychiatric symptoms (NPS) in dementia but can also develop in persons with normal cognition (NC) or mild cognitive impairment (MCI). The later-life emergence and persistence of apathy as part of the MBI syndrome may be a driving factor for dementia risk. Therefore, we investigated MBI-apathy-associated progression to dementia, and effect modification by sex, race, cognitive diagnosis, and apolipoprotein E (APOE) genotype. Dementia-free National Alzheimer's Coordinating Center participants were stratified by persistent apathy status, based on Neuropsychiatric Inventory (NPI)-Questionnaire scores at two consecutive visits. Hazard ratios (HRs) for incident dementia for MBI-apathy and NPI-apathy relative to no NPS, and MBI-apathy relative to no apathy, were determined using Cox proportional hazards regressions, adjusted for baseline age, sex, years of education, race, cognitive diagnosis, and APOE genotype. Interactions with relevant model covariates were explored. Of the 3932 participants (3247 with NC), 354 had MBI-apathy. Of all analytic groups, MBI-apathy had the greatest dementia incidence (HR = 2.69, 95% confidence interval [CI]: 2.15-3.36, P<0.001). Interaction effects were observed between cognitive diagnosis and APOE genotype with the NPS group. The contribution of apathy to dementia risk was greater in NC (HR = 5.91, 95% CI: 3.91-8.93) than in MCI (HR = 2.16, 95% CI: 1.69-2.77, interaction P<0.001) and in all APOE genotypes, was greatest in APOE ɛ3 (HR = 4.25, 95% CI: 3.1-5.82, interaction P<0.001). Individuals with MBI-apathy have a markedly elevated risk for future dementia, especially when symptoms emerge in those with NC. Both cognitive status and APOE genotype are important moderators in the relationship between MBI-apathy and incident dementia. MBI-apathy may represent a group in whom apathy is a preclinical or prodromal manifestation of dementia and identify a precision medicine target for preventative interventions.

Self-Experienced Cognitive Function in the Digital Era: Are Older Adults at Risk of Subjective Cognitive Decline?

Older adults often find it difficult to use everyday technology proficiently. We hypothesized that these difficulties would be exacerbated in those with subjective cognitive decline (SCD), that is, self-perceived worsening of cognitive functions that has been associated with increased risk of future dementia. Here we investigated the relationship between SCD symptom burden and technology proficiency. A nation-wide sample of adults (N=483) ages 50-79 (66.5% female; 14.5% age >70) completed an online survey via a crowdsourcing website, Amazon Mechanical Turk. The survey included the Subjective Cognitive Decline Questionnaire (SCD-Q MyCog) (0-25, M=4.71, SD=5.77), questions about respondents’ proficiency with computer, smartphone, and tablet (4-12, M=9.72, SD=1.97), and the PROMIS depression (M=13.18, SD=6.32) and anxiety (M=13.04, SD=5.68) scales. Linear regression was used to examine the ability of technology proficiency to predict SCD score. We also probed the interaction of technology proficiency with age ( <70 vs. >70 years), and adjusted for covariates. We found that the age/technology interaction (B=-0.80), older age (B=7.49), lower education (B=-1.08), higher depression (B=0.20) and anxiety (B=0.16) symptoms predicted higher SCD burden (R-squared=.16). For respondents >70 years low technology proficiency predicted high SCD burden (B=-.79) whereas for those <70 years no relationship was found. Our study draws attention to older adults’ self-experienced cognitive function in the digital era. The association between low technology proficiency and SCD may signal the adverse impact of the digital era on those who experienced technology only later in life. It is equally possible that declining technology proficiency is an indicator of emerging neurodegenerative disease.