Biomedical subjects

Paul K Crane

Publications and source records attributed to Paul K Crane.

18 recordsLinked to original sources

PubMed2026

Genetic modifiers of APOE-ε4-associated cognitive decline.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including 29,354 non-Hispanic White and 3,424 non-Hispanic Black individuals. Our primary outcome is late-life cognition, measured using harmonized composite scores for memory, executive function, and language, modeled as continuous traits reflecting both normative cognitive aging and disease-related decline. We identify two genome-wide significant loci in APOE-ε4 carriers, reaching genome-wide significance for executive function. These loci also demonstrate nominal associations across the other domains, suggesting broad effects on cognition. In non-carriers, we identify a genome-wide significant association at ITGB8 restricted to executive function, and another locus associated with language. We further link these loci to SEMA6D, GRIN3A, and ITGB8 through expression and methylation databases. Post-GWAS analyses implicate additional genes including SLCO1A2, and DNAH11. Genetic correlation analyses reveal differences by APOE-ε4 status for immune-related traits, suggesting immune-related predispositions may exacerbate cognitive risk in APOE-ε4 carriers.

Humans↗

PubMed2025

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.

BACKGROUND: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. RESULTS: We identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.13 (LHX5-AS1). We additionally identify three population-specific loci with genome-wide significance at/near PTPRK and GRB14 in HIS and KIAA0825 in NHW. Pathway analysis implicates multiple amyloid regulation pathways and the classical complement pathway. Genes at/near our novel loci have known roles in neuronal development (LRRC4C, LHX5-AS1, and PTPRK) and insulin receptor activity regulation (GRB14). CONCLUSIONS: Using cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of diverse ancestry in GWAS, we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed. Continued expansion into larger multi-ancestry studies will provide even more power for further elucidating the genomics of late-onset Alzheimer's disease.

Humans↗

PubMed2024

Biobank-wide association scan identifies risk factors for late-onset Alzheimer's disease and endophenotypes.

Rich data from large biobanks, coupled with increasingly accessible association statistics from genome-wide association studies (GWAS), provide great opportunities to dissect the complex relationships among human traits and diseases. We introduce BADGERS, a powerful method to perform polygenic score-based biobank-wide association scans. Compared to traditional approaches, BADGERS uses GWAS summary statistics as input and does not require multiple traits to be measured in the same cohort. We applied BADGERS to two independent datasets for late-onset Alzheimer's disease (AD; n=61,212). Among 1738 traits in the UK biobank, we identified 48 significant associations for AD. Family history, high cholesterol, and numerous traits related to intelligence and education showed strong and independent associations with AD. Furthermore, we identified 41 significant associations for a variety of AD endophenotypes. While family history and high cholesterol were strongly associated with AD subgroups and pathologies, only intelligence and education-related traits predicted pre-clinical cognitive phenotypes. These results provide novel insights into the distinct biological processes underlying various risk factors for AD.

Alzheimer Disease↗

PubMed2018

Sex-specific genetic predictors of Alzheimer's disease biomarkers.

Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aβ42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (β = - 0.03, p = 4.25 × 10-8; β = 0.03, p = 3.97 × 10-8) than males (β = - 0.02, p = 0.009; β = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (β = 0.05, p = 4.57 × 10-10) compared to males (β = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale = 0.047; pmale = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD's genetic architecture.

Aged, 80 and over↗

PubMed2011

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Rapid detection of differential item functioning in assessments of health-related quality of life: The Functional Assessment of Cancer Therapy.

REASON FOR STUDY: Differential item functioning (DIF) occurs when a test item functions differently in different groups when controlling for the level of the underlying construct measured by the test. DIF assessment is a first step in the evaluation of test bias. We sought to demonstrate a rapid hybrid approach to DIF detection by determining the presence and scale-level impact of DIF related to eight covariates in four domains measured by the Functional Assessment of Cancer Therapy (FACT). MAJOR FINDINGS: The number of items found with DIF in each domain depended on the criterion chosen to define the presence of DIF. With a few exceptions, scale-level differential functioning was similar regardless of the criteria chosen. For physical well-being, there was relevant scale-level differential functioning related only to race. For social and family well-being, there was relevant scale-level differential functioning related to each of the covariates. For emotional well-being, there was relevant scale-level differential functioning related to ethnicity, language, and race. For functional well-being, there was relevant scale-level differential functioning related to ethnicity, race, education, and self- vs. interviewer-administration. PRINCIPAL CONCLUSIONS: Our rapid hybrid approach to DIF detection may be broadly applicable in other studies of health-related quality of life.

Adolescent↗

PubMed2006

Factor analysis techniques for assessing sufficient unidimensionality of cancer related fatigue.

BACKGROUND: Fatigue is the most common unrelieved symptom experienced by people with cancer. The purpose of this study was to examine whether cancer-related fatigue (CRF) can be summarized using a single score, that is, whether CRF is sufficiently unidimensional for measurement approaches that require or assume unidimensionality. We evaluated this question using factor analysis techniques including the theory-driven bi-factor model. METHODS: Five hundred and fifty five cancer patients from the Chicago metropolitan area completed a 72-item fatigue item bank, covering a range of fatigue-related concerns including intensity, frequency and interference with physical, mental, and social activities. Dimensionality was assessed using exploratory and confirmatory factor analysis (CFA) techniques. RESULTS: Exploratory factor analysis (EFA) techniques identified from 1 to 17 factors. The bi-factor model suggested that CRF was sufficiently unidimensional. CONCLUSIONS: CRF can be considered sufficiently unidimensional for applications that require unidimensionality. One such application, item response theory (IRT), will facilitate the development of short-form and computer-adaptive testing. This may further enable practical and accurate clinical assessment of CRF.

Aged↗

PubMed2006

A 37-item shoulder functional status item pool had negligible differential item functioning.

OBJECTIVE: Measures of shoulder function may differ by dominance of affected shoulder, surgical history, gender, or race. We present a technique for determining whether observed differences in function between groups are due to biased test items or real differences in function. STUDY DESIGN AND SETTING: Four hundred patients who were receiving rehabilitation for a variety of shoulder impairments completed a survey of shoulder function. Thirty-seven items measuring shoulder function were analyzed for differential item functioning (DIF) related to demographic characteristics using an ordinal logistic regression (OLR) and item response theory (IRT) approach. When DIF was identified in an item, we modified the IRT analysis to calibrate item parameters separately in appropriate demographic groups. We compared adjusted and unadjusted patient ability measures in each demographic group. RESULTS: Several items were found to have a modest amount of DIF related to the different demographic characteristics, especially gender; however, adjusting measures for DIF had little impact on overall measures of shoulder function and made almost no difference in average shoulder function across demographic groups. CONCLUSION: In this pool of shoulder function items, adjustment for DIF made almost no difference in measures of function across demographic groups.

Activities of Daily Living↗

PubMed2006

Differential item functioning related to education and age in the Italian version of the Mini-mental State Examination.

BACKGROUND: Differential item functioning (DIF) exists when test item responses by members of different demographic groups are statistically different when controlling for ability. DIF may indicate item bias. Our objective was to determine whether items from the Italian Mini-mental State Examination (MMSE) had DIF related to educational attainment, age, gender and occupation. We were also interested in exploring the significance of DIF in screening tests. METHODS: In a two-stage study from Granarolo, Italy, residents over age 61 (n = 495) were evaluated with the Italian MMSE. Those with MMSE scores of 28 or lower were further evaluated for dementia. MMSE results were coded in 10 item bundles. We used ordinal logistic regression to determine whether item bundles had DIF. RESULTS: Six of the 10 MMSE item bundles had DIF in educational attainment subgroups. Four of these six bundles also had DIF related to age. Items that required literacy were much harder for those with lower educational attainment. CONCLUSIONS: DIF related to education appeared at as few as 3 years of formal schooling. These findings suggest cautious interpretation of data from studies using the Italian MMSE in populations with heterogeneous educational backgrounds. DIF is especially troublesome for two-stage studies that use screening tests.

Aged↗

PubMed2006

Association between obesity and psychiatric disorders in the US adult population.

BACKGROUND: Epidemiologic data suggest an association between obesity and depression, but findings vary across studies and suggest a stronger relationship in women than men. OBJECTIVE: To evaluate the relationship between obesity and a range of mood, anxiety, and substance use disorders in the US general population. DESIGN: Cross-sectional epidemiologic survey. SETTING: Nationally representative sample of US adults. PARTICIPANTS: A total of 9125 respondents who provided complete data on psychiatric disorder, height, and weight. Response rate was 70.9%. MAIN OUTCOME MEASURES: Participants completed an in-person interview, including assessment of a range of mental disorders (assessed using the World Health Organization Composite International Diagnostic Interview) and height and weight (by self-report). RESULTS: Obesity (defined as body mass index [calculated as weight in kilograms divided by the square of height in meters] of > or =30) was associated with significant increases in lifetime diagnosis of major depression (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09-1.35), bipolar disorder (OR, 1.47; 95% CI, 1.12-1.93), and panic disorder or agoraphobia (OR, 1.27; 95% CI, 1.01-1.60). Obesity was associated with significantly lower lifetime risk of substance use disorder (OR, 0.78; 95% CI, 0.65-0.93). Subgroup analyses found no difference in these associations between men and women, but the association between obesity and mood disorder was strongest in non-Hispanic whites (OR, 1.38; 95% CI, 1.20-1.59) and college graduates (OR, 1.44; 95% CI, 1.14-1.81). CONCLUSIONS: Obesity is associated with an approximately 25% increase in odds of mood and anxiety disorders and an approximately 25% decrease in odds of substance use disorders. Variation across demographic groups suggests that social or cultural factors may moderate or mediate the association between obesity and mood disorder.

Adult↗

PubMed2006

Differential item functioning analysis with ordinal logistic regression techniques. DIFdetect and difwithpar.

INTRODUCTION: We present an ordinal logistic regression model for identification of items with differential item functioning (DIF) and apply this model to a Mini-Mental State Examination (MMSE) dataset. We employ item response theory ability estimation in our models. Three nested ordinal logistic regression models are applied to each item. Model testing begins with examination of the statistical significance of the interaction term between ability and the group indicator, consistent with nonuniform DIF. Then we turn our attention to the coefficient of the ability term in models with and without the group term. If including the group term has a marked effect on that coefficient, we declare that it has uniform DIF. We examined DIF related to language of test administration in addition to self-reported race, Hispanic ethnicity, age, years of education, and sex. METHODS: We used PARSCALE for IRT analyses and STATA for ordinal logistic regression approaches. We used an iterative technique for adjusting IRT ability estimates on the basis of DIF findings. RESULTS: Five items were found to have DIF related to language. These same items also had DIF related to other covariates. DISCUSSION: The ordinal logistic regression approach to DIF detection, when combined with IRT ability estimates, provides a reasonable alternative for DIF detection. There appear to be several items with significant DIF related to language of test administration in the MMSE. More attention needs to be paid to the specific criteria used to determine whether an item has DIF, not just the technique used to identify DIF.

Bias↗

PubMed2006

Diabetes case identification methods applied to electronic medical record systems: their use in HIV-infected patients.

OBJECTIVE: New onset diabetes mellitus type 2 is increasing among HIV-infected patients in the era of potent antiretroviral therapy. Accurately identifying HIV-infected patients with a diagnosis of diabetes in electronic medical record systems will facilitate the study of patients with this disease. STUDY DESIGN AND SETTING: We examined electronic medical record data for all patients who initiated care at an HIV clinic between 1/1/1997 and 12/31/2001 to identify potential cases of diabetes. Case identification methods included clinician-coded diagnoses, medications, and HbA1c and glucose levels. Diabetes diagnoses were verified by clinician documentation in an electronic medical record progress note. Test characteristics of each case identification method were calculated. RESULTS: 53 cases of diabetes were identified among the cohort of 1,441 patients. Use of clinician-coded diagnoses alone or combined with other methods was the most sensitive method for identifying diabetes cases. Clinician-coded diagnoses were also the best method as assessed by standard receiver operator characteristic plots. A significant attenuation of odds ratios for associations with diabetes were found for case identification methods with imperfect specificity such as serum glucose levels. CONCLUSIONS: This study demonstrates that electronic medical record data can be used to accurately identify HIV-infected patients with diabetes. The optimal method applied will depend on the goals of a particular study.

Academic Medical Centers↗

PubMed2005

Simulated computerized adaptive test for patients with shoulder impairments was efficient and produced valid measures of function.

BACKGROUND AND OBJECTIVE: To test unidimensionality and local independence of a set of shoulder functional status (SFS) items, develop a computerized adaptive test (CAT) of the items using a rating scale item response theory model (RSM), and compare discriminant validity of measures generated using all items (theta(IRT)) and measures generated using the simulated CAT (theta(CAT)). STUDY DESIGN AND SETTING: We performed a secondary analysis of data collected prospectively during rehabilitation of 400 patients with shoulder impairments who completed 60 SFS items. RESULTS: Factor analytic techniques supported that the 42 SFS items formed a unidimensional scale and were locally independent. Except for five items, which were deleted, the RSM fit the data well. The remaining 37 SFS items were used to generate the CAT. On average, 6 items were needed to estimate precise measures of function using the SFS CAT, compared with all 37 SFS items. The theta(IRT) and theta(CAT) measures were highly correlated (r = .96) and resulted in similar classifications of patients. CONCLUSION: The simulated SFS CAT was efficient and produced precise, clinically relevant measures of functional status with good discriminating ability.

Activities of Daily Living↗

PubMed2004

The efficacy and safety of sibutramine for weight loss: a systematic review.

BACKGROUND: The primary goal of weight loss is to prevent or reduce obesity-associated morbidity and mortality by improving cardiovascular and metabolic risk factors. We conducted a systematic review to assess the efficacy and safety of sibutramine hydrochloride for weight loss. METHODS: In April 2002, we searched MEDLINE, EMBASE, the Cochrane Library, and 7 other computerized bibliographic search tools using the keywords "sibutramine," "Meridia," and "Reductil" (in all languages and all available years). The authors and the manufacturer were contacted. We reviewed randomized placebo-controlled trials of sibutramine, 10 to 20 mg/d, in obese adults. Methodological quality was assessed. RESULTS: A total of 29 trials had sufficient data for analysis after including unpublished data from 10 authors. The summary mean differences in weight loss, sibutramine minus placebo, for the 3-month and 1-year trials were -2.78 kg (95% confidence interval, -2.26 to -3.29 kg) and -4.45 kg (95% confidence interval, -3.62 to -5.29 kg), respectively. The 6-month trials were statistically heterogeneous, and evidence of publication bias was found. One trial found that sibutramine maintains weight loss better than placebo at 2 years. Weight loss with sibutramine was associated with modest increases in heart rate and blood pressure, small improvements in high-density lipoprotein cholesterol and triglycerides levels, and, among diabetic patients, small improvements in glycemic control. There was no direct evidence that sibutramine reduces obesity-associated morbidity or mortality. CONCLUSIONS: Sibutramine is effective in promoting weight loss. Weight loss with sibutramine is associated with both positive and negative changes in cardiovascular and metabolic risk factors. There is insufficient evidence to accurately determine the long-term risk-benefit profile for sibutramine.

Appetite Depressants↗

PubMed2004

Test bias in a cognitive test: differential item functioning in the CASI.

Assessment of test bias is important to establish the construct validity of tests. Assessment of differential item functioning (DIF) is an important first step in this process. DIF is present when examinees from different groups have differing probabilities of success on an item, after controlling for overall ability level. Here, we present analysis of DIF in the Cognitive Assessment Screening Instrument (CASI) using data from a large cohort study of elderly adults. We developed an ordinal logistic regression modelling technique to assess test items for DIF. Estimates of cognitive ability were obtained in two ways based on responses to CASI items: using traditional CASI scoring according to the original test instructions as well as using item response theory (IRT) scoring. Several demographic characteristics were examined for potential DIF, including ethnicity and gender (entered into the model as dichotomous variables), and years of education and age (entered as continuous variables). We found that a disappointingly large number of items had DIF with respect to at least one of these demographic variables. More items were found to have DIF with traditional CASI scoring than with IRT scoring. This study demonstrates a powerful technique for the evaluation of DIF in psychometric tests. The finding that so many CASI items had DIF suggests that previous findings of differences between groups in cognitive functioning as measured by the CASI may be due to biased test items rather than true differences between groups. The finding that IRT scoring diminished the impact of DIF is discussed. Some preliminary suggestions for how to deal with items found to have DIF in cognitive tests are made. The advantages of the DIF detection techniques we developed are discussed in relation to other techniques for the evaluation of DIF.

Bias↗

PubMed2004

Spanish and English Neuropsychological Assessment Scales (SENAS): further development and psychometric characteristics.

The Spanish and English Neuropsychological Assessment Scales were devised to be a broad set of psychometrically matched measures with equivalent Spanish and English versions. Study 1 in this report used item response theory methods to refine scales. Results strongly supported psychometric matching across English and Spanish versions and, for most scales, within English and Spanish versions. Study 2 supported in both English and Spanish subsamples the 6-domain model of ability that guided scale construction. Study 3 examined differential item functioning (DIF) of one scale (Object Naming) in relation to education, ethnicity, gender, and age. Effects of DIF on scale-level ability scores were limited. Results demonstrate an empirically guided psychometric approach to test construction for multiethnic and multilingual test applications.

Cognition↗

PubMed2004

The coming epidemic of obesity in elderly Americans.

OBJECTIVES: To estimate the prevalence of obesity in elderly Americans in 2010 and to discuss the health and economic implications of these estimates. DESIGN: Three methods of generating future point-prevalence estimates using data from consecutive cross-sectional studies. SETTING: All regions of the United States. PARTICIPANTS: Estimates were based on five nationally representative surveys of the adult population of the United States, conducted from 1960 to 2000, and population estimates from the U.S. Census Bureau. MEASUREMENTS: Changes in obesity (body mass index (BMI) > or =30 kg/m(2)) and normal weight (BMI <25 kg/m(2)) prevalence for men and women by 10-year U.S. birth cohorts were examined. The prevalence of obesity and normal weight in the elderly in 2010 was estimated under three different scenarios of obesity prevalence change. RESULTS: It was estimated that the prevalence of obesity in adults aged 60 and older will increase from 32.0% in 2000 to 37.4% in 2010 (range 33.6-39.6%). The number of obese adults aged 60 and older will increase from 14.6 to 20.9 million (range 18.8-22.2 million). Similarly, it was estimated that the prevalence of normal weight among adults aged 60 and older will decrease from 30.6% in 2000 to 26.7% in 2010 (range 31.0-24.7%). CONCLUSION: The prevalence of obesity in elderly Americans will likely continue to increase, challenging healthcare delivery and financing systems in the United States.

Aged↗

PubMed2004

Subjective memory deterioration and future dementia in people aged 65 and older.

OBJECTIVES: To study whether subjective memory deterioration is associated with future dementia in older people. DESIGN: A population-based prospective cohort study begun in 1994 with biennial follow-up interviews. SETTING: Community-based members of Group Health Cooperative, a large health maintenance organization in the Seattle area. PARTICIPANTS: A sample of 1,883 subjects, dementia free, aged 65 and older, who scored 91 or higher on the 100-point Cognitive Ability Screening Instrument (CASI) at study entry. MEASUREMENTS: Subjective memory was assessed by asking whether memory had changed on 5-point Likert scales (e.g., 1=definitely improved, 3=no change, 5=definitely deteriorated) with regard to five items: remembering names, faces, friends, and appointments and judging the time. The items were summed for a possible total score ranging from 5 to 25. Subjective memory deterioration was defined as present if the total score was 20 or above. Cognitive performance was measured using the CASI. Incident dementia cases were identified using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. RESULTS: Of 1,883 subjects, 126 developed dementia during 5 years of follow-up. Subjective memory deterioration was associated with cognitive decline and incident dementia. Age modified the association between subjective memory deterioration and future dementia. For persons reporting subjective memory deterioration at the ages of 70, 75, and 80, the hazard ratios of developing dementia were 6.0 (95% confidence interval (CI)=2.1-18), 3.2 (95% CI=1.6-6.2) and 1.6 (95% CI=0.86-3.1), respectively. CONCLUSION: Subjective memory deterioration was found to precede the development of dementia in older people with normal cognitive screening results. These findings suggest that a high level of subjective memory deterioration in persons with normal objective cognitive function may identify a subset of individuals at greater risk for developing dementia.

Aged↗