Risk Of Incident Dementia Research Articles

Transition to healthier lifestyle associated with reduced risk of incident dementia and decreased hippocampal atrophy

BackgroundResearch has estimated the associations of lifestyle at one-time point with the risk of dementia and hippocampal volume, but the impact of lifestyle transition on dementia and hippocampal volume remains unclear. This study aims to examine the associations of lifestyle transition with the risk of dementia and hippocampal volume. MethodsBased on data from the UK Biobank, a weighted lifestyle score was constructed by incorporating six lifestyle factors. Within each baseline lifestyle group (i.e., healthy, intermediate, and unhealthy), lifestyle transition was classified into decline, maintenance, and improvement. Cox proportional hazard regression was used to estimate the association of lifestyle transition and incident dementia (N = 16,305). A multiple linear regression model was used to estimate the association between lifestyle transition and hippocampal volume (N = 5849). ResultsDuring a median follow-up period of 8.6 years, 120 (0.7 %) dementia events were documented. Among participants with healthy baseline lifestyles, the improvement group had a lower risk of incident dementia (HR: 0.18, 95 % CI: 0.04–0.81) and a larger hippocampal volume (β = 111.69, P = 0.026) than the decline group. Similar results were observed among participants with intermediate baseline lifestyles regarding dementia risk but not hippocampal volume. No benefits were observed in the improvement group among those with unhealthy baseline lifestyles. LimitationsA lower incidence of dementia than other cohort study and this may have resulted in an underestimation of the risk of dementia. ConclusionsEarlier transitions to healthier lifestyle were associated with reduced risk of incident dementia and decreased hippocampal atrophy.

Risk of Alzheimer's disease is associated with longitudinal changes in plasma biomarkers in the multi-ethnic Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP) cohort.

Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in predicting cognitive impairment and AD needs examination. In 628 CU individuals from a multi-ethnic cohort, amyloid beta (Aβ)42, Aβ40, phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured in plasma. Higher baseline levels of p-tau181/Aβ42 ratio were associated with an increased risk of incident dementia. A biomarker pattern (with elevated Aβ42/Aβ40 but low p-tau181/Aβ42) was associated with decreased dementia risk. Compared to CU, participants who developed MCI or dementia had a rapid decrease in this protective biomarker pattern reflecting AD-specific pathological change. Elevated levels of AD biomarker p-tau181/Aβ42, by itself or combined with a low Aβ42/Aβ40 level, predicts clinically diagnosed AD. Individuals with a rapid change in these biomarkers may need close monitoring for the potential downward trajectory of cognition. We discuss a multi-ethnic, urban community study of elderly individuals. The study consisted of a longitudinal assessment over 6 years with repeated clinical assessments. The study used blood-based biomarkers as predictors of mild cognitive impairment and Alzheimer's disease.

Association between surgery and rate of incident dementia in older adults: A population-based retrospective cohort study.

The risk of incident dementia after surgery in older adults is unclear. The study objective was to examine the rate of incident dementia among older adults after elective surgery compared with a matched nonsurgical control group. We conducted a population-based, propensity-matched retrospective cohort study using data from linked administrative databases in Ontario, Canada. All community-dwelling individuals aged 66 years and older who underwent one of five major elective surgeries between April 1, 2007 and March 31, 2011 were included. Each surgical patient was matched 1:1 on surgical specialty of the surgeon at consultation, age, sex, fiscal year of entry, and propensity score with a patient who attended an outpatient visit with a surgeon of the same surgical specialty but did not undergo surgery. Patients were followed for up to 5 years after cohort entry for the occurrence of a new dementia diagnosis, defined from administrative data. Cause-specific hazard models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between surgery and the hazard of incident dementia. Subgroup and sensitivity analyses were performed. A total of 27,878 individuals (13,939 matched pairs) were included in the analysis. A total of 640 (4.6%) individuals in the surgical group and 965 (6.9%) individuals in the control group developed dementia over the 5-year follow-up period. Individuals who underwent surgery had a reduced rate of incident dementia compared with their matched nonsurgical controls (HR 0.88; 95% CI 0.80-0.97; p = 0.01). This association was persistent in most subgroups and after sensitivity analyses. Elective surgery did not increase the rate of incident dementia when compared with matched nonsurgical controls. This could be an important consideration for patients and surgeons when elective surgery is considered.

Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records

Introduction4.2 million individuals in the UK have type 2 diabetes, a known risk factor for dementia and mild cognitive impairment (MCI). Diabetes treatment may modify this association, but existing evidence...

Racial and ethnic disparities in social isolation and 11-year dementia risk among older adults in the United States.

Social isolation has been implicated in the development of cognitive impairment, but research on this association remains limited among racial-ethnic minoritized populations. Our study examined the interplay between social isolation, race-ethnicity and dementia. We analyzed 11 years (2011-2021) of National Health and Aging Trends Study (NHATS) data, a prospective nationally representative cohort of U.S. Medicare beneficiaries aged 65 years and older. Dementia status was determined using a validated NHATS algorithm. We constructed a longitudinal score using a validated social isolation variable for our sample of 6,155 community-dwelling respondents. Cox regression determined how the interaction between social isolation and race-ethnicity was associated with incident dementia risk. Average longitudinal frequency of social isolation was higher among older Black (27.6%), Hispanic (26.6%) and Asian (21.0%) respondents than non-Hispanic White (19.1%) adults during the 11-year period (t = -7.35, p < .001). While a higher frequency of social isolation was significantly associated with an increased (approximately 47%) dementia risk after adjusting for sociodemographic covariates (adjusted hazard ratio [aHR] = 1.47, 95% CI [1.15, 1.88], p < .01), this association was not significant after adjusting for health covariates (aHR = 1.21, 95% CI [0.96, 1.54], p = .11). Race-ethnicity was not a significant moderator in the association between social isolation and dementia. Older adults from racial-ethnic minoritized populations experienced a higher longitudinal frequency of social isolation. However, race-ethnicity did not moderate the positive association observed between social isolation and dementia. Future research is needed to investigate the underlying mechanisms contributing to racial-ethnic disparities in social isolation and to develop targeted interventions to mitigate the associated dementia risk.

Sex Difference in the Association between Prior Fracture and Subsequent Risk of Incident Dementia: A Longitudinal Cohort Study.

A history of fracture has been associated with increased risk of dementia; however, it is uncertain whether sex difference exists in the association between prior fracture and subsequent risk of incident dementia. To investigate whether sex modified the relationship between prior fracture and subsequent risk of dementia. Prospective cohort study. UK Biobank. 496,331 participants (54.6% women) free of dementia at baseline. History of fracture was self-reported via touchscreen questionnaires at baseline. The primary outcome was all-cause dementia. Both any fracture and fragility fracture were significantly associated with an increased risk of subsequent all-cause dementia in men (adjusted hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.14-1.43; adjusted HR: 1.48; 95% CI: 1.18-1.87, respectively), but not in women (adjusted HR: 1.04; 95% CI 0.95-1.15; adjusted HR: 1.01; 95% CI: 0.87-1.18, respectively); and these sex-differences were significant (P interaction = 0.006; P interaction = 0.007, respectively). The sex differences in the impacts of different fracture sites (including upper limb, lower limb, spine, and multiple sites) were consistent on all-cause dementia. This study demonstrated that prior fracture was associated with an increased risk of dementia in men but not in women, and the sex difference was significant. Previous fracture may be an important marker for identifying subsequent dementia in middle-aged and older men.

Liver integrity and the risk of Alzheimer's disease and related dementias.

We examined midlife (1990-1992, mean age 57) and late-life (2011-2013, mean age 75) nonalcoholic fatty liver disease (NAFLD) and aminotransferase with incident dementia risk through 2019 in the Atherosclerosis Risk in Communities (ARIC) Study. We characterized NAFLD using the fatty liver index and fibrosis-4, and we categorized aminotransferase using the optimal equal-hazard ratio (HR) approach. We estimated HRs for incident dementia ascertained from multiple data sources. Adjusted for demographics, alcohol consumption, and kidney function, individuals with low, intermediate, and high liver fibrosis in midlife (HRs: 1.45, 1.40, and 2.25, respectively), but not at older age, had higher dementia risks than individuals without fatty liver. A U-shaped association was observed for alanine aminotransferase with dementia risk, which was more pronounced in late-life assessment. Our findings highlight dementia burden in high-prevalent NAFLD and the important feature of late-life aminotransaminase as a surrogate biomarker linking liver hypometabolism to dementia. Highlights Although evidence of liver involvement in dementia development has been documented in animal studies, the evidence in humans is limited. Midlife NAFLD raised dementia risk proportionate to severity. Late-life NAFLD was not associated with a high risk of dementia. Low alanine aminotransferase was associated with an elevated dementia risk, especially when measured in late life.

TOXIC CHEMICAL EMISSIONS AND DEMENTIA RISK: RESULTS FROM THE CARDIOVASCULAR HEALTH COGNITION STUDY

Abstract Air pollution is a modifiable risk factor for dementia. Yet, studies on specific forms of air pollution (e.g., toxic chemical emissions from industrial facilities) and dementia risk are underexplored. We examined associations between toxicity-weighted concentrations of industrial pollution and dementia outcomes among a large, multi-site cohort of older adults. Participants (n=2,770) were ≥ 65 years old (M=75.3, SD=5.1 years) from the Cardiovascular Health Cognition Study. Toxicity-weighted concentrations were estimated using the Risk Screening Environmental Indicator (RSEI) model which incorporates total reported chemical emissions with toxicity, fate, and transport models. Estimates were aggregated to participants’ baseline census tract, averaged across 1988-1992, and log10-transformed. Dementia status was clinically adjudicated in 1998-1999 (M=5.2 person-periods) by subtype (all-cause, Alzheimer’s, vascular, mixed). We assessed whether RSEI-estimated toxicity-weighted concentrations were associated with: 1) odds of prevalent dementia and 2) incident dementia risk by subtype. After adjusting for individual and neighborhood-level covariates, a 1-unit increase in log10-toxicity was associated with a 34% increase in the odds of prevalent dementia (OR=1.34, 95% CI: 1.01, 1.78). In discrete-time survival models, each 1-unit increase in log10-toxicity was associated with a 65% increased hazard of vascular dementia (HR=1.65, 95% CI: 1.04, 2.61) but was not significantly associated with all-cause, Alzheimer’s disease, or mixed dementia. Living in regions with higher toxic air emissions was associated with greater odds of prevalent dementia and a heightened risk of incident vascular dementia. Results suggest that the RSEI model may be a novel screening tool for examining associations between toxic chemical releases and dementia risk.

NEIGHBORHOOD HEALTH CARE FACILITIES AND INCIDENT DEMENTIA: RESULTS FROM THE EINSTEIN AGING STUDY

Abstract Though access to health care is associated with improved chronic health outcomes, data on dementia risk are limited. From the Ecological Model of Aging, limited access to health care facilities may be associated with increased likelihood of developing dementia through poor management of comorbidities. The current study aims to investigate the association between the density of neighborhood health care facilities and incident dementia. Participants were community-dwelling older adults, systematically recruited from Bronx, NY (N=1,461, mean age=78.4; mean follow-ups=4.6 years; 68% non-Hispanic White, 26% non-Hispanic Black). Density of health care facilities in each participant’s Census Tract was derived from the National Establishment Time-Series data. We used Cox proportional hazards models using age as the time scale and adjusted for sex, race, education, income, and neighborhood deprivation. Incident dementia developed in 10% of the sample. Older adults living in the areas with lower density of health care facilities, compared to those living areas with a higher density of health care facilities, were at increased risk for incident dementia (HR=1.79, 95% CI=[1.12, 2.87] for lowest vs. highest tertile; HR=1.65, 95% CI=[1.02, 2.66] for intermediate vs. highest tertile). Further controlling for cardiovascular and other comorbidities did not change the pattern of results. The current results suggest that unequal distribution of health care facilities across geographic locations may help account for cognitive health disparities among older adults. Future studies will need to identify behavioral and individual-level mechanisms (e.g., healthcare use, better treatment before disease occurs) in the association between neighborhood health care facilities and dementia.

NEW DIRECTIONS IN RESEARCH ON THE DYNAMICS OF PURPOSE IN LIFE AND COGNITIVE AGING

Abstract Purpose in life is the feeling that one’s life is goal oriented and has direction. There is converging, replicated evidence that having a greater sense of purpose in life is associated with better cognitive aging outcomes, including less cognitive decline across middle and older adulthood and lower risk of incident dementia. Emerging evidence also suggests that cognitive function may likewise support purpose in life. This symposium highlights recent advances on the dynamics between purpose in life and cognition across varying time scales and populations. Kim will describe the association between purpose in life and the maintenance of better cognitive function across six years in older adulthood and moderators of this association. Nelson and Bergeman will describe how cognitive function supported purpose in life through the uncertainty of the Covid-19 pandemic and moderators of this association. Pfund and colleagues will report on the bidirectional associations between purpose and cognition in older adulthood across four longitudinal samples using a coordinated data analytic approach. Finally, Sutin and colleagues will report on an ecological momentary assessment study that found that in moments when participants felt more purposeful, they had faster processing speed. Collectively, these talks emphasize the dynamic and often bidirectional relation between purpose in life and cognitive function. This work will help stimulate research to better understand purpose and cognitive health and how to leverage purpose in life for healthier cognitive aging outcomes.

The predictive validity of a Brain Care Score for dementia and stroke: data from the UK Biobank cohort.

The 21-point Brain Care Score (BCS) was developed through a modified Delphi process in partnership with practitioners and patients to promote behavior changes and lifestyle choices in order to sustainably reduce the risk of dementia and stroke. We aimed to assess the associations of the BCS with risk of incident dementia and stroke. The BCS was derived from the United Kingdom Biobank (UKB) baseline evaluation for participants aged 40-69 years, recruited between 2006-2010. Associations of BCS and risk of subsequent incident dementia and stroke were estimated using Cox proportional hazard regressions, adjusted for sex assigned at birth and stratified by age groups at baseline. The BCS (median: 12; IQR:11-14) was derived for 398,990 UKB participants (mean age: 57; females: 54%). There were 5,354 incident cases of dementia and 7,259 incident cases of stroke recorded during a median follow-up of 12.5 years. A five-point higher BCS at baseline was associated with a 59% (95%CI: 40-72%) lower risk of dementia among participants aged <50. Among those aged 50-59, the figure was 32% (95%CI: 20-42%) and 8% (95%CI: 2-14%) for those aged >59 years. A five-point higher BCS was associated with a 48% (95%CI: 39-56%) lower risk of stroke among participants aged <50, 52% (95%CI, 47-56%) among those aged 50-59, and 33% (95%CI, 29-37%) among those aged >59. The BCS has clinically relevant and statistically significant associations with risk of dementia and stroke in approximately 0.4 million UK people. Future research includes investigating the feasibility, adaptability and implementation of the BCS for patients and providers worldwide.

Association between non-cystic fibrosis bronchiectasis and the risk of incident dementia: A nationwide cohort study

Background Chronic lung diseases, such as chronic obstructive pulmonary disease or asthma, are associated with an increased risk of dementia. However, few data are available regarding the risk of dementia in individuals with bronchiectasis. Objectives To explore the association between bronchiectasis and the risk of incident dementia using a longitudinal population-based cohort. Methods A total of 4,068,560 adults older than 50 years without previous dementia were enrolled from the Korean National Health Insurance Service database in 2009. They were followed up until the date of the diagnosis of dementia or December 31, 2020. The study exposure was the diagnosis of bronchiectasis, and the primary outcome was incident dementia comprising Alzheimer’s disease and vascular dementia. Results During the median follow-up duration of 9.3 years, the incidence of all-cause dementia was 1.6-fold higher in individuals with bronchiectasis than in those without bronchiectasis (15.0 vs. 9.3/1000 person-years, p &lt; .001). In the multivariable Cox regression analysis, the risk of all dementia was significantly higher in individuals with bronchiectasis than in those without bronchiectasis (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 1.04–1.14). In a subgroup analysis by dementia type, individuals with bronchiectasis had an increased risk of Alzheimer’s disease compared to those without bronchiectasis (aHR 1.07, 95% CI 1.01–1.12); the risk of vascular dementia did not significantly differ between the two groups (aHR 1.05, 95% CI 0.90–1.21). Conclusion Bronchiectasis was associated with an increased risk of dementia, especially Alzheimer’s disease.

Retinal microvasculature and risk of incident dementia over a 10‐year period: results from the 3C‐Alienor population‐based study

AbstractBackgroundThe retina and the brain microvasculatures share many anatomical and physiological similarities; thus, retinal microvasculature could represent a potential screening tool for cerebrovascular and neurodegenerative diseases. Changes in retinal microvasculature have been associated with dementia in previous studies. However, all the previous studies analyzing retinal vascular network features in relation to dementia or Alzheimer Disease (AD) were cross‐sectional. This study aimed to explore the longitudinal relationship between retinal microvascular features and dementia incidence over a 10‐year follow‐up period.MethodWe included 617 participants from the Three‐City (3C) population‐based cohort and its ancillary ophthalmological study, the Alienor study. Quantitative retinal vascular features (caliber, tortuosity, fractal dimension) were assessed at baseline in the Alienor study using the semi‐automated Singapore I Vessel Assessment (SIVA) software; dementia was actively screened and diagnosed over a 10‐year period. Cox proportional‐hazards models were used to estimate the risk of incident dementia and its main etiologies (i.e., probable or possible AD and mixed or vascular dementia) associated with retinal vascular features.ResultThe mean age of the participants was 79.5 years (SD 4.4) and 66.6% were women. During the follow‐up (median of 7.2 years), 134 participants developed dementia (87 probable or possible AD and 38 mixed or vascular dementia). In multivariate models adjusted for the main potential confounders (socio‐demographic factors, vascular co‐morbidities and Apolipoprotein ε4 allele), increased arteriolar tortuosity was associated with increased risk of dementia (HR per SD increase = 1.26, 95%CI: 1.07; 1.50). Despite some trends, retinal calibers were not significantly associated with dementia all‐cause. When considering the different etiologies of dementia, wider retinal venular calibers were associated with mixed or vascular dementia, but not with Alzheimer’s disease. Fractal dimensions were not associated with dementia.ConclusionChanges in retinal microvasculature were associated with risk of incident dementia. More works are needed to replicate and determine which features could help identifying persons at risk of future dementia at an early stage, and to examine the specific processes that might be involved according to dementia etiology.

Cataract, cataract surgery, and risk of incident dementia: a prospective cohort study of 300,823 participants

AbstractBackgroundConsidering the increasing rate of cataract surgery and postoperative efficacy, the cataract may be one of the most modifiable risk factors for dementia if surgery reverses the increased risk of dementia caused by cataract.MethodWe used multivariate Cox proportional hazard regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations, with healthy controls as a reference. The same method was used to explore the effects of surgery on the dementia outcomes of cataract patients.ResultMultivariable Cox proportional hazard models showed that the non‐surgical cataract group had a 21.4% increased risk of ACD (HR: 1.214, 95% CI = 1.012‐1.456, P = 0.037) and a 47.9% increased risk of AD (HR: 1.479, 95% CI = 1.105‐1.981, P = 0.009) in the fully adjusted model. However, there was no difference in dementia risk between the cataract surgery group and the healthy control. Cataract surgery was associated with decreased risk of ACD (HR: 0.632, 95% CI = 0.421‐0.947, P = 0.026) and AD (HR: 0.399, 95% CI = 0.196‐0.812, P = 0.011) compared with non‐surgical group.ConclusionOur study supports the hypothesis that cataract surgery reverses the risk of dementia, providing new insights into the prevention and treatment of dementia. Cataract should be considered a significant modifiable risk factor for dementia in dementia prevention strategies.

Clinical Manifestations.

Impulse dyscontrol, i.e., excessive motor activity and/or physical and verbal aggression is common in dementia. However, impulse dyscontrol can also emerge in advance of dementia, but is often normalized due to age, or framed as a psychiatric condition. Thus, the association between these symptoms and incident dementia is unclear. Mild behavioral impairment (MBI) leverages risk associated with later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a high-risk group for incident dementia. Impulse dyscontrol is one of five MBI domains. Here, in dementia-free participants, we assessed risk of progression to dementia in MBI-impulse dyscontrol and conventionally-measured impulse dyscontrol symptoms (Conv-ID). Dementia-free National Alzheimer Coordinating Centre participants were included. Neuropsychiatric Inventory Questionnaire irritability, agitation, and aberrant motor behavior items were used to identify impulse dyscontrol. MBI-impulse dyscontrol was operationalized by symptom presence at more than two-thirds of pre-dementia study visits (symptom persistence criterion) in those with no history of psychiatric disorders (symptom emergence criterion). Conv-ID required symptoms only at baseline without consideration of past psychiatric history. Kaplan-Meier survival curves and Cox proportional hazards models, adjusted for age, sex, education, race, and APOE-e4 status, were generated to compare survival probability and dementia incidence rates of MBI-impulse dyscontrol and Conv-ID to No-NPS. The sample comprised 1,884 MBI-impulse dyscontrol (age = 74.5±9.7; 40.9% female), 3,676 Conv-ID (age = 71.0±9.4; 47.0% female), and 6,362 No-NPS participants (age = 71.0±10.3; 64.7% female) (Table 1). MBI-impulse dyscontrol had lower dementia-free survival (p<0.0001) and 2.23-fold greater dementia incidence compared to No-NPS (CI:1.99-2.50, p<0.001, Figure 1(A)); Conv-ID had lower dementia-free survival (p<0.0001) and 1.39-fold greater dementia incidence compared to No-NPS (CI:1.25-1.54, p<0.001, Figure 1(B)). Compared with a conventional approach to assess agitated and impulsive behaviors, MBI-impulse dyscontrol was associated with greater dementia incidence. Applying the MBI criteria of later-life emergence and persistence of symptoms provides a more specific approach to identify those at risk for incident dementia, who might otherwise be dismissed due to normalization of these behaviors in older persons or labelled with a psychiatric condition. This approach may allow for earlier implementation of preventative measures, pharmacological and non-pharmacological, improving outcomes and quality of life for patients and their caregivers.

Association of birth weight with incident dementia: The Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study

AbstractBackgroundEarly life factors, such as birth weight (BW), may have long‐term health consequences, but the importance of these factors in dementia risk is poorly understood. Our objective was to prospectively examine the association of BW with dementia incidence over mid‐ to late‐adulthood in the ARIC study. We hypothesized that participants who report lower BW experience more incident dementia than participants who report normal BW, and this association may differ by race.Method10,789 participants who were dementia‐free at ARIC baseline (Visit 1: 1987‐1989; ages 45‐64) and followed through 2019 were included. Participants were asked their BW through standard interviews at Visit 4 (1996‐1998), but if unable to recall, they selected their BW category: low (&lt;5.5 lbs.), medium (normal) (5.5‐9.0 lbs.), or high (&gt;9.0 lbs.), and to identify if they were premature (yes/no). Adjudicated dementia cases from baseline through 2019 were classified using in‐person cognitive evaluations, informant interviews, and phone assessments as well as hospitalization codes and death certificate codes. The associations between having high or low (vs medium) BW and dementia, or premature birth status and dementia were investigated using Cox proportional hazards models, with testing for interaction by race.ResultOur overall population was 54 yo at baseline, 56% female, and 20% Black; 2,255 dementia cases were identified over a median of 28.2 years. Participants who reported a low BW had 1.2 times (95% CI 1.02, 1.41) increased risk of incident dementia compared to those with medium BW in demographic‐ and APOE‐adjusted models (Table 1). This association was no longer significant when the model additionally adjusted for vascular risk factors. The risk for dementia was not increased among participants who reported having been born premature (vs not premature). When stratified by race, the risk of incident dementia was elevated in Black participants reporting high (vs medium) BW, but not in White participants reporting high BW (p‐interaction = 0.006) (Table 2).ConclusionIn this cohort, low BW was associated with risk of dementia in minimally adjusted models. The association was attenuated after accounting for vascular risk factors. High BW was associated with risk of dementia in Black participants only.

Apathy, depression and risk of incident dementia in community‐dwelling older adults

AbstractBackgroundApathy, which may be a risk or prognostic factor for incident dementia in older adults, has been little investigated in cognitively normal populations and has largely lacked consideration of comorbid depression. Understanding the potential role of apathy in the development of dementia has also been limited by short follow‐up periods, and cohorts with restricted age ranges (below 80 years). Our aim was to investigate whether self‐report apathy predicted incident dementia over 14 years, when adjusting for comorbid depression in a population‐based sample of older adults (aged 70‐90) without dementia at baseline.MethodThe Sydney Memory and Ageing Study included 1,037 community‐dwelling participants at baseline (median age 78 years (range 70‐90); 55% female). Assessments included the self‐report Geriatric Depression Scale, from which apathy (GDS‐3A) and depression (GDS‐12D) subscores were obtained. Incident dementia was diagnosed by expert panel clinical consensus at biennial assessments for up to 14 years. Cox survival analyses examined risk conferred by apathy and depression for incident dementia separately, and then included both in the same model as concurrent predictors. Analyses were initially unadjusted. The fully adjusted model controlled for baseline age, sex, education, non‐English speaking background, global cognition (MMSE), APOE4 status and health conditions.ResultOf the 858 participants with follow‐up data, 271 developed dementia (31.6%), over an average 9 years follow‐up. Self‐report apathy and depression separately predicted higher risk for dementia in the unadjusted models (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.05, 2.00; HR 1.47, 95% CI 1.06, 2.04, respectively). When including both apathy and depression concurrently in the model, apathy remained a significant risk factor, but depression did not. In the fully adjusted model, apathy no longer significantly predicted incident dementia. Post‐hoc analyses using split‐half groups by age showed the effect was attenuated only for younger participants (below 78 years).ConclusionApathy was associated with increased risk of incident dementia, independently of depression, over 14 years in a community‐dwelling population‐based cohort of older adults. This novel evidence of long‐term risk addresses prior limitations in the literature and implicates apathy as a prognostic marker for dementia, particularly with increasing age.

Kidney function and risk of incident dementia in 202,702 UK Biobank participants

AbstractBackgroundPoorer kidney function could represent a novel modifiable risk factor for dementia, however previous findings are inconclusive. In the current study, we utilized a large population‐based cohort with long follow‐up to investigate whether glomerular filtration rate (GFR), an indicator of kidney function, and albuminuria, an indicator of kidney damage, were associated with an increased risk of all‐cause dementia.MethodThe sample consisted of 202,702 UK Biobank participants aged ≥60 years and free from dementia and end‐stage kidney disease at baseline between 2006‐2010. Estimated GFR was derived from serum creatinine and cystatin C (eGFRcr‐cys) and categorized as ≥90 (normal/high function), 60‐89 (mildly decreased function) and &lt;60 ml/min/1.73m2 (moderately/severely decreased function). Albuminuria was defined using the urinary albumin to creatinine ratio (ACR). ACR was categorized into &lt;3 (normal/mildly increased), 3‐30 (moderately increased), and &gt;300 (severely increased) mg/mmol. Incident dementia was determined through cohort‐wide linkage to hospital and death records. The associations were assessed using Cox proportional‐hazard models adjusted for age, sex, ethnicity, socioeconomic status, education, household income, country, smoking status, alcohol intake, body mass index, hypertension, diabetes, and APOE‐ε4 allele status.ResultOver 15 years of follow‐up, 6,042 participants developed incident dementia. The fully‐adjusted Hazard Ratios (HR) were 1.00 (95% Confidence Interval [CI] 0.94‐1.06) and 1.42 (95% CI 1.28‐1.58) for eGFRcr‐cys 60‐89 and &lt;60 respectively, compared to ≥90 ml/min/1.73m2. Moderately/severely decreased eGFRcr‐cys remained associated with incident dementia after restricting to participants with more than 10 years of follow‐up (HR = 1.33, 95% CI 1.13‐1.56). The HRs for moderate and severely increased ACR were 1.16 (95% CI 1.07‐1.26) and 2.24 (95% CI 1.79‐2.80), respectively, compared to normal/mildly increased ACR (&lt;3mg/mmol). Dose‐response associations were observed when combining eGFRcr‐cys and ACR, with those in the severest eGFRcr‐cys and ACR group having the greatest risk of dementia (HR = 4.70, 95% CI 2.34‐9.43).ConclusionKidney dysfunction and albuminuria were associated with a higher risk of incident all‐cause dementia. These findings provide additional evidence that kidney dysfunction could be a potential modifiable risk factor for dementia or target for identifying those at high risk of the condition.

Association between poor periodontal health and 15‐year risk of incident dementia

AbstractBackgroundPoor oral health, particularly tooth loss, has been highlighted as a potential modifiable risk factor for dementia. However, longitudinal evidence concerning the association of poor periodontal health with dementia is limited. This study examines the impact of poor periodontal health on 15‐year risk of incident dementia.MethodThis study included 4596 dementia‐free and dentate (i.e., having ≥1 teeth remaining) participants, aged 30‐93 years, from population‐based Finnish Health 2000 Survey. Periodontal health at baseline was evaluated through bleeding on probing (BOP), periodontal pocket depths (PPD), and alveolar bone loss (ABL). BOP for each sextant and PPD for each tooth (excluding third molars and residual roots) were recorded clinically during oral examination. Based on BOP, participants were dichotomized into having ≥1 sextant with BOP versus no BOP.Tooth with PPD of ≥4mm was considered as having deepened periodontal pocket. Based on PPD, participants were dichotomized into having ≥1 teeth with deepened PPD versus no PPD. ABL for each tooth was examined through orthopantomographs and defined as vertical bone loss extending apically to at least the middle third of tooth root. Based on ABL, participants were dichotomized into having ≥1 teeth with ABL versus no ABL. Dementia diagnosis until 2015 was retrieved from national health registers.Cox proportional regression was conducted and adjusted for age, gender, education, cardiovascular risk, socioeconomic status, depression, alcohol consumption, c‐reactive protein, and overall tooth count. Sensitivity analysis accounting for potential reverse causality bias was conducted by excluding incident dementia during the first five years of follow‐up.Result183 participants developed dementia over 15 years. Fully adjusted hazard ratio among participants with ≥1 sextant with BOP was 1.15 (CI:0.80‐1.65), with ≥1 teeth having deepened PPD was 0.94 (CI:0.67–1.31), and with ≥1 teeth having ABL was 0.97 (CI:0.64–1.49). Findings from sensitivity analysis for potential reverse causality bias corroborated with results for main analyses.ConclusionPreliminary findings indicate no association of BOP, PPD, or ABL with 15‐year dementia risk. However, further well‐designed longitudinal studies with more comprehensive periodontal assessment (e.g., clinically diagnosed periodontitis and severity of periodontitis) are warranted to conclusively assess its impact on dementia risk.

The association of bone mineral density and dementia: the Rotterdam Study

AbstractBackgroundLow bone mineral density and dementia commonly co‐occur in the elderly, with bone loss accelerating in dementia patients due to physical inactivity and poor nutrition. However, uncertainty persists over the extent to which bone loss already exists prior to the onset of dementia. Therefore, we investigated how dementia risk was affected by bone mineral density at various skeletal regions in community‐dwelling older adults.MethodIn a prospective population‐based cohort study, bone mineral density at the femoral neck, lumbar spine, and total body and the trabecular bone score were obtained using dual‐energy X‐ray absorptiometry (DXA) in 3,651 participants free from dementia between 2002‐2005. Persons at risk of dementia were followed up until 1 January 2020. For analyses of the association between bone mineral density at baseline and the risk of incident dementia, we used Cox proportional‐hazards regression analyses, adjusting for age, sex, educational attainment, physical activity, smoking status, body mass index, systolic blood pressure, diastolic blood pressure, cholesterol level, high‐density lipoprotein cholesterol, history of comorbidities (stroke and diabetes mellitus), and APOE genotype.ResultAmong the 3,651 participants (median age 72.3±10.0 years, 57.9% women), 688 (18.8%) developed incident dementia during a median of 11.1 years, of whom 528 (76.7%) developed Alzheimer’s disease. During the whole follow‐up, participants with lower bone mineral density at the femoral neck (per SD decrease) were more likely to develop all‐cause dementia (Hazard ratio [HR] total follow‐up: 1.12, 95% Confidential interval [CI]: 1.02‐1.23) and Alzheimer’s disease (HR total follow‐up: 1.14, 95% CI: 1.02‐1.28). Within the first ten years following baseline, the risk of dementia was greatest for groups with the lowest tertile of bone mineral density (femoral neck bone mineral density, HR0‐10years 2.03; 95% CI, 1.39–2.96; total body bone mineral density, HR0‐10years 1.42; 95% CI, 1.01‐2.02; trabecular bone score, HR0‐10years 1.59; 95% CI, 1.11‐2.28).ConclusionIn conclusion, participants with low femoral neck and total body bone mineral density and low trabecular bone score were more likely to develop dementia. Further studies should focus on the predictive ability of bone mineral density for dementia.