Diabetic Retinopathy and Dementia Association, Beyond Diabetes Severity.

PURPOSE: To investigate whether associations between diabetic retinopathy (DR) and dementia and Alzheimer's disease (AD) remain significant after controlling for several measures of diabetes severity. DESIGN: Retrospective cohort study. METHODS: Adult Changes in Thought (ACT) is a prospective cohort study of adults aged ≥65 years, randomly selected and recruited from the membership rolls of Kaiser Permanente Washington, who are dementia free at enrollment and followed biennially until incident dementia. The ACT participants were included in this study if they had type 2 diabetes mellitus at enrollment or developed it during follow-up, and data were collected through September, 2018 (3516 person-years of follow-up). Diabetes was defined by ≥ 2 diabetes medication fills in 1 year. Diagnosis of DR was based on International Classification of Diseases Ninth and Tenth Revision codes. Estimates of microalbuminuria, long-term glycemia, and renal function from longitudinal laboratory records were used as indicators of diabetes severity. Alzheimer's disease and dementia were diagnosed using research criteria at expert consensus meetings. RESULTS: A total of 536 participants (median baseline age 75 [interquartile range 71-80], 54% women) met inclusion criteria. Significant associations between DR >5 years duration with dementia (hazard ratio 1.81 [95% CI 1.23, 2.65]) and AD (1.80 [1.15, 2.82]) were not altered by adjustment for estimates of microalbuminuria, long-term glycemia, and renal function (dementia: 1.69 [1.14, 2.50]; AD: 1.73 [1.10, 2.74]). CONCLUSIONS: Among people with type 2 diabetes, DR itself appears to be an important biomarker of dementia risk in addition to glycemia and renal complications.

Association Between Cataract Extraction and Development of Dementia.

IMPORTANCE: Visual function is important for older adults. Interventions to preserve vision, such as cataract extraction, may modify dementia risk. OBJECTIVE: To determine whether cataract extraction is associated with reduced risk of dementia among older adults. DESIGN, SETTING, AND PARTICIPANTS: This prospective, longitudinal cohort study analyzed data from the Adult Changes in Thought study, an ongoing, population-based cohort of randomly selected, cognitively normal members of Kaiser Permanente Washington. Study participants were 65 years of age or older and dementia free at enrollment and were followed up biennially until incident dementia (all-cause, Alzheimer disease, or Alzheimer disease and related dementia). Only participants who had a diagnosis of cataract or glaucoma before enrollment or during follow-up were included in the analyses (ie, a total of 3038 participants). Data used in the analyses were collected from 1994 through September 30, 2018, and all data were analyzed from April 6, 2019, to September 15, 2021. EXPOSURES: The primary exposure of interest was cataract extraction. Data on diagnosis of cataract or glaucoma and exposure to surgery were extracted from electronic medical records. Extensive lists of dementia-related risk factors and health-related variables were obtained from study visit data and electronic medical records. MAIN OUTCOMES AND MEASURES: The primary outcome was dementia as defined by Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. Multivariate Cox proportional hazards regression analyses were conducted with the primary outcome. To address potential healthy patient bias, weighted marginal structural models incorporating the probability of surgery were used and the association of dementia with glaucoma surgery, which does not restore vision, was evaluated. RESULTS: In total, 3038 participants were included (mean [SD] age at first cataract diagnosis, 74.4 (6.2) years; 1800 women (59%) and 1238 men (41%); and 2752 (91%) self-reported White race). Based on 23 554 person-years of follow-up, cataract extraction was associated with significantly reduced risk (hazard ratio, 0.71; 95% CI, 0.62-0.83; P < .001) of dementia compared with participants without surgery after controlling for years of education, self-reported White race, and smoking history and stratifying by apolipoprotein E genotype, sex, and age group at cataract diagnosis. Similar results were obtained in marginal structural models after adjusting for an extensive list of potential confounders. Glaucoma surgery did not have a significant association with dementia risk (hazard ratio, 1.08; 95% CI, 0.75-1.56; P = .68). Similar results were found with the development of Alzheimer disease dementia. CONCLUSIONS AND RELEVANCE: This cohort study found that cataract extraction was significantly associated with lower risk of dementia development. If validated in future studies, cataract surgery may have clinical relevance in older adults at risk of developing dementia.

Associations Between Retinal Artery/Vein Occlusions and Risk of Vascular Dementia.

BACKGROUND: Vascular disease is a risk factor for Alzheimer's disease (AD) and related dementia in older adults. Retinal artery/vein occlusion (RAVO) is an ophthalmic complication of systemic vascular pathology. Whether there are associations between RAVO and dementia risk is unknown. OBJECTIVE: To determine whether RAVOs are associated with an increased risk of developing vascular dementia or AD. METHODS: Data from Adult Changes in Thought (ACT) study participants were analyzed. This prospective, population-based cohort study followed older adults (age ≥65 years) who were dementia-free at enrollment for development of vascular dementia or AD based on research criteria. RAVO diagnoses were extracted from electronic medical records. Cox-regression survival analyses were stratified by APOEɛ4 genotype and adjusted for demographic and clinical factors. RESULTS: On review of 41,216 person-years (4,743 participants), 266 (5.6%) experienced RAVO. APOEɛ4 carriers who developed RAVO had greater than four-fold higher risk for developing vascular dementia (Hazard Ratio [HR] 4.54, 95% Confidence Interval [CI] 1.86, 11.10, p = 0.001). When including other cerebrovascular disease (history of carotid endarterectomy or transient ischemic attack) in the model, the risk was three-fold higher (HR 3.06, 95% CI 1.23, 7.62). No other conditions evaluated in the secondary analyses were found to confound this relationship. There was no effect in non-APOEɛ4 carriers (HR 1.03, 95% CI 0.37, 2.80). There were no significant associations between RAVO and AD in either APOE group. CONCLUSION: Older dementia-free patients who present with RAVO and carry the APOEɛ4 allele appear to be at higher risk for vascular dementia.

Using Varying Diagnostic Criteria to Examine Mild Cognitive Impairment Prevalence and Predict Dementia Incidence in a Community-Based Sample.

Lack of a unitary operational definition of mild cognitive impairment (MCI) has resulted in mixed prevalence rates and unclear predictive validity regarding conversion to dementia and likelihood of reversion. We examined 1,721 nondemented participants aged 65 and older from the Adult Changes in Thought (ACT) community-based cohort. Participants were followed longitudinally through biennial visits (average years assessed = 5.38). Categorization of MCI was based on: 1) deviation of neuropsychological test scores from a benchmark based on either standard or individualized expectations of a participant's mean premorbid cognitive ability, and 2) cutoff for impairment (1.0 versus 1.5 standard deviations [sd] below benchmark). MCI prevalence ranged from 56-92%; using individualized benchmarks and less stringent cutoffs produced higher rates. During follow-up, 17% of the cohort developed dementia. Examination of sensitivity, specificity, and predictive validity revealed that the criterion of 1.5 sd from the standardized benchmark was optimal, but still had limited predictive validity. Participants meeting this criterion at their first visit were three times more likely to develop dementia and this increased to seven times if participants had this diagnosis at the second timepoint as well. Those who did not have an MCI diagnosis at their first visit, but did at their second, had a significant increase of risk (but to a lesser extent than those diagnosed at both visits), while those who had an MCI diagnosis at their first visit, but not their second, did not have a significantly increased risk. These results highlight how assessing MCI stability greatly improves prediction of risk.

Associations between recent and established ophthalmic conditions and risk of Alzheimer's disease.

INTRODUCTION: Identifying ophthalmic diseases associated with increased risk of Alzheimer's disease (AD) may enable better screening and understanding of those at risk of AD. METHODS: Diagnoses of glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) were based on International Classification of Diseases, 9th revision, codes for 3877 participants from the Adult Changes in Thought study. The adjusted hazard ratio for developing probable or possible AD for recent (within 5 years) and established (>5 years) diagnoses were assessed. RESULTS: Over 31,142 person-years of follow-up, 792 AD cases occurred. The recent and established hazard ratio were 1.46 (P = .01) and 0.87 (P = .19) for glaucoma, 1.20 (P = .12) and 1.50 (P < .001) for AMD, and 1.50 (P = .045) and 1.50 (P = .03) for DR. DISCUSSION: Increased AD risk was found for recent glaucoma diagnoses, established AMD diagnoses, and both recent and established DR. People with certain ophthalmic conditions may have increased AD risk.

Characterization of dementia and Alzheimer's disease in an older population: updated incidence and life expectancy with and without dementia.

OBJECTIVES: We estimated dementia incidence rates, life expectancies with and without dementia, and percentage of total life expectancy without dementia. METHODS: We studied 3605 members of Group Health (Seattle, WA) aged 65 years or older who did not have dementia at enrollment to the Adult Changes in Thought study between 1994 and 2008. We estimated incidence rates of Alzheimer's disease and dementia, as well as life expectancies with and without dementia, defined as the average number of years one is expected to live with and without dementia, and percentage of total life expectancy without dementia. RESULTS: Dementia incidence increased through ages 85 to 89 years (74.2 cases per 1000 person-years) and 90 years or older (105 cases per 1000 person-years). Life expectancy without dementia and percentage of total life expectancy without dementia decreased with age. Life expectancy with dementia was longer in women and people with at least a college degree. Percentage of total life expectancy without dementia was greater in younger age groups, men, and those with more education. CONCLUSIONS: Efforts to delay onset of dementia, if successful, would likely benefit older adults of all ages.

Incidence rates of dementia, Alzheimer disease, and vascular dementia in the Japanese American population in Seattle, WA: the Kame Project.

There are few studies on the incidence of dementia in representative minority populations in the United States; however, no population-based study has been conducted on Japanese American women. We identified 3045 individuals aged 65+ with at least 1 parent of Japanese descent living in King County, WA in the period 1992 to 1994, of whom 1836 were dementia-free and were examined every 2 years (1994 to 2001) to identify incident cases of all dementias, Alzheimer disease (AD), vascular dementia (VaD), and other dementias. Cox regression was used to examine associations with age, sex, years of education, and apolipoprotein (APOE)-ε4. Among 173 incident cases of dementia, the overall rate was 14.4/1000/y, with rates being slightly higher among women (15.9/1000) than men (12.5/1000). Rates roughly doubled every 5 years for dementia and AD; the age trend for VaD and other dementias was less consistent. Sex was not significantly related to incidence of dementia or its subtypes in adjusted models. There was a trend for an inverse association with increasing years of education. APOE-ε4 was a strong risk factor for all dementias [hazard ratio (HR)=2.89; 95% confidence interval (CI), 1.88-4.46], AD (HR=3.27; 95% CI, 2.03-5.28), and VaD (HR=3.33; 95% CI, 1.34-8.27). This study is the first to report population-based incidence rates for both Japanese American men and women.

Strategies to promote safe medication administration in assisted living settings.

Assisted living (AL) provides lower cost, less institutional environments than skilled nursing facilities, yet less professional oversight, despite the high prevalence of chronic conditions among residents. Unlicensed staff administer large quantities of medications daily, and medication management is one of the three top quality issues in AL, with error rates ranging from 10% to 40%. This qualitative study described AL provider views on medication safety and strategies used to promote safety in medication administration. The sample included 96 participants representing all parties involved in medication administration (i.e., medication aides, administrators, RNs, consulting pharmacists, primary care providers) in 12 AL settings in three states. Core themes were the importance of medication safety, unique contextual factors in AL, and strategies used to promote medication safety. This study has implications for research on interventions to improve medication safety at the individual, facility, and policy levels.

Relationship between longitudinal measures of renal function and onset of dementia in a community cohort of older adults.

OBJECTIVES: To evaluate the association between dynamic measures of renal function ascertained over time and onset of dementia. DESIGN: Prospective community cohort study. SETTING: Group Health, Seattle, Washington. PARTICIPANTS: Two thousand nine hundred sixty-eight adults aged 65 and older followed for the development of dementia over a median of 6.0 years (interquartile range 3.1-10.1 years). MEASUREMENTS: Time-varying measures of renal function were constructed based on 49,340 serum creatinine measurements and included average estimated glomerular filtration rate (eGFR), eGFR trajectory, and variability in eGFR around this trajectory over 5-year exposure windows. The association between these three eGFR exposure measures and risk of dementia was estimated using a Cox regression model adjusted for other participant characteristics. Time-varying measures of urine protein by dipstick were also adjusted for in sensitivity analyses. RESULTS: Participants with a lower eGFR had a higher incidence of dementia, but this did not reach statistical significance in adjusted analyses (omnibus P = .14). There were trends toward a higher adjusted incidence of dementia in participants with positive eGFR trajectories (omnibus P = .07) and greater variability in eGFR (omnibus P = .04) over time. The results of sensitivity analyses, including those in which time-varying measures of proteinuria were included, were consistent with those of the primary analysis. CONCLUSION: In a community cohort of older adults followed for a median of 6 years, strong associations were not found between measures of kidney disease severity and progression and incident dementia.

Insulin and sex interactions in older adults with mild cognitive impairment.

Alzheimer's disease (AD) and other dementias are likely preceded by a protracted preclinical state. Thus, identification of biomarkers that signal potential points of intervention during this prodromal phase (during which patients are largely able to compensate for their cognitive deficits) is of paramount importance. Insulin is a pancreatic hormone with potent central nervous system effects, and insulin dysregulation has been implicated in the pathogenesis of both AD and vascular dementia. The aim of the current study was to determine whether circulating insulin differs as a function of mild cognitive impairment (MCI) diagnosis, and whether this relationship is mediated by sex and apolipoprotein E (APOE) genotype. A sample of 549 nondemented participants aged 65 and over from the Adult Changes in Thought community-based cohort underwent cognitive testing and blood draw to determine fasting levels of plasma insulin. Subjects were categorized as having normal cognitive functioning, amnestic MCI, or nonamnestic MCI. Results showed that the relationship between insulin and diagnostic category is moderated by sex, such that men with nonamnestic or amnestic MCI have higher fasting plasma insulin than cognitively normal men, while women with amnestic MCI have lower fasting plasma insulin than cognitively normal women. Exploratory analyses suggest that APOE ε4 genotype may further influence the relationship between sex and insulin. Future research will help determine whether insulin dysregulation results in differential effects on vascular function and AD pathology as a function of sex and/or APOE genotype.