Subsequent Diagnosis Of Dementia Research Articles

A pathway linking pulse pressure to dementia in adults with Down syndrome.

Adults with Down syndrome are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease and is linked to a diagnosis of dementia in adults with Down syndrome via structural imaging markers of cerebrovascular disease and atrophy. The study included participants with Down syndrome from the Alzheimer's Disease - Down Syndrome study (n = 195, age = 50.6 ± 7.2 years, 44% women, 18% diagnosed with dementia). Higher pulse pressure was associated with greater global, parietal and occipital white matter hyperintensity volume but not with enlarged perivascular spaces, microbleeds or infarcts. Using a structural equation model, we found that pulse pressure was associated with greater white matter hyperintensity volume, which in turn was related to increased neurodegeneration, and subsequent dementia diagnosis. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with Down syndrome despite the low likelihood of frank hypertension.

An investigation of neuropsychiatric symptoms, contextual factors, and antidepressant treatment as risk factors for dementia development in people with mild cognitive impairment.

While some people with mild cognitive impairment (MCI) progress to dementia, many others show no progression. The aim of this study was to identify factors associated with risk of dementia development in this population. A large naturalistic retrospective cohort study was assembled from mental healthcare records in a south London catchment. Patients were selected at first recorded diagnosis of MCI and subsequent dementia diagnosis was ascertained from case notes or death certificate, excluding those with dementia diagnoses and deaths within 6months of MCI diagnosis. A range of demographic and clinical characteristics were ascertained around MCI diagnosis and Cox proportional hazards models were used to investigate independent predictors of dementia, focussing on neuropsychiatric symptoms, contextual factors, and antidepressant treatment. Of 2250 patients with MCI, 236 (10.5%) developed dementia at least 6months after MCI diagnosis. Aside from older age, lower cognitive function, and activities of daily living impairment, impaired social relationships and recorded loneliness were associated with a higher risk of developing dementia. Patients of Black (compared to White) ethnicity were at a lower risk. For depression and antidepressant receipt, only tricyclic use compared to no antidepressant use was associated with an increased dementia risk. No evidence was found for co-morbid affective disorders or different antidepressant classes as risk factors for dementia development following MCI diagnosis, but loneliness and social impairment were independent predictors and would be worth evaluating as targets for interventions to delay progression.

Towards a Clearer Causal Question Underlying the Association Between Cancer and Dementia.

Several observational studies have described an inverse association between cancer diagnosis and subsequent dementia risk. Multiple biologic mechanisms and potential biases have been proposed in attempts to explain this association. One proposed explanation is the opposite expression of Pin1 in cancer and dementia, and we use this explanation and potential drug target to illustrate the required assumptions and potential sources of bias for inferring an effect of Pin1 on dementia risk from analyses measuring cancer diagnosis as a proxy for Pin1 expression. We used data from the Rotterdam Study, a population-based cohort. We estimate the association between cancer diagnosis (as a proxy for Pin1) and subsequent dementia diagnosis using two different proxy methods and with confounding and censoring for death addressed with inverse probability weights. We estimate and compare the complements of a weighted Kaplan-Meier survival estimator at 20 years of follow-up. Out of 3634 participants, 899 (25%) were diagnosed with cancer, of whom 53 (6%) had dementia, and 567 (63%) died. Among those without cancer, 15% (411) were diagnosed with dementia, and 667 (24%) died over follow-up. Depending on the confounding and selection bias control, and the way in which cancer was used as a time-varying proxy exposure, the risk ratio for dementia diagnosis ranged from 0.71 (95% confidence interval [CI] = 0.49, 0.95) to 1.1 (95% CI = 0.79, 1.3). Being explicit about the underlying mechanism of interest is key to maximizing what we can learn from this cancer-dementia association given available or readily collected data, and to defining, detecting, and preventing potential biases.

Lower-Body Fractures and the Risk of Dementia: A Nationwide Population-Based Study.

The association between physical activity and dementia has been shown in various observational studies. We aimed to determine the risk of dementia in the elderly with lower-body fractures. We reconstructed a population-based matched cohort from the National Health Insurance Service-Senior Cohort data set that covers 511,953 recipients of medical insurance in South Korea. Overall 53,776 subjects with lower-body fractures were identified during 2006-2012, and triplicate control groups were matched randomly by sex, age, and years from the index date for each subject with a fracture. There were 3,573 subjects (6.6%) with and 7,987 subjects (4.9%) without lower-body fractures who developed dementia from 2008 up to 2015. Lower-body fractures were independently associated with a subsequent dementia diagnosis with a higher adjusted hazard ratio (aHR) (1.55, 95% confidence interval [CI]=1.49-1.62) compared with upper-body fractures (aHR=1.19, 95% CI=1.14-1.23). These results support the protective role of physical activity against dementia and highlight the importance of promoting fracture prevention in the elderly.

Association of Postoperative Delirium With Incident Dementia and Graft Outcomes Among Kidney Transplant Recipients.

Kidney transplant (KT) recipients have numerous risk factors for delirium, including those shared with the general surgical population (eg, age and major surgery) and transplant-specific factors (eg, neurotoxic immunosuppression medications). Evidence has linked delirium to long-term dementia risk in older adults undergoing major surgery. We sought to characterize dementia risk associated with post-KT delirium. Using the United States Renal Data System datasets, we identified 35 800 adult first-time KT recipients ≥55 y. We evaluated risk factors for delirium using logistic regression. We evaluated the association between delirium and incident dementia (overall and by subtype: Alzheimer's, vascular, and other/mixed-type), graft loss, and death using Fine and Gray's subhazards models and Cox regression. During the KT hospitalization, 0.9% of recipients were diagnosed with delirium. Delirium risk factors included age (OR = 1.40, 95% CI, 1.28-1.52) and diabetes (OR = 1.38, 95% CI, 1.10-1.73). Delirium was associated with higher risk of death-censored graft loss (aHR = 1.52, 95% CI, 1.12-2.05) and all-cause mortality (aHR = 1.53, 95% CI, 1.25-1.89) at 5 y post-KT. Delirium was also associated with higher risk of dementia (adjusted subhazard ratio [aSHR] = 4.59, 95% CI, 3.48-6.06), particularly vascular dementia (aSHR = 2.51, 95% CI, 1.01-6.25) and other/mixed-type dementia (aSHR = 5.58, 95% CI, 4.24-7.62) subtypes. The risk of all-type dementia associated with delirium was higher for younger recipients aged between 55 and 64 y ( Pinteraction = 0.01). Delirium is a strong risk factor for subsequent diagnosis of dementia among KT recipients, particularly those aged between 55 and 64 y at the time of transplant. Patients experiencing posttransplant delirium might benefit from early interventions to enhance cognitive health and surveillance for cognitive impairment to enable early referral for dementia care.

Association of Early-, Middle-, and Late-Life Depression With Incident Dementia in a Danish Cohort

Late-life depressive symptoms are associated with subsequent dementia diagnosis and may be an early symptom or response to preclinical disease. Evaluating associations with early- and middle-life depression will help clarify whether depression influences dementia risk. To examine associations of early-, middle-, and late-life depression with incident dementia. This was a nationwide, population-based, cohort study conducted from April 2020 to March 2023. Participants included Danish citizens from the general population with depression diagnoses who were matched by sex and birth year to individuals with no depression diagnosis. Participants were followed up from 1977 to 2018. Excluded from analyses were individuals followed for less than 1 year, those younger than 18 years, or those with baseline dementia. Depression was defined using diagnostic codes from the International Classification of Diseases (ICD) within the Danish National Patient Registry (DNPR) and Danish Psychiatric Central Research Register (DPCRR). Incident dementia was defined using ICD diagnostic codes within the DPCRR and DNPR. Cox proportional hazards regression was used to examine associations between depression and dementia adjusting for education, income, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, anxiety disorders, stress disorders, substance use disorders, and bipolar disorder. Analyses were stratified by age at depression diagnosis, years since index date, and sex. There were 246 499 individuals (median [IQR] age, 50.8 [34.7-70.7] years; 159 421 women [64.7%]) with diagnosed depression and 1 190 302 individuals (median [IQR] age, 50.4 [34.6-70.0] years; 768 876 women [64.6%]) without depression. Approximately two-thirds of those diagnosed with depression were diagnosed before the age of 60 years (684 974 [67.7%]). The hazard of dementia among those diagnosed with depression was 2.41 times that of the comparison cohort (95% CI, 2.35-2.47). This association persisted when the time elapsed from the index date was longer than 20 to 39 years (hazard ratio [HR], 1.79; 95% CI, 1.58-2.04) and among those diagnosed with depression in early, middle, or late life (18-44 years: HR, 3.08; 95% CI, 2.64-3.58; 45-59 years: HR, 2.95; 95% CI, 2.75-3.17; ≥60 years: HR, 2.31; 95% CI, 2.25-2.38). The overall HR was greater for men (HR, 2.98; 95% CI, 2.84-3.12) than for women (HR, 2.21; 95% CI, 2.15-2.27). Results suggest that the risk of dementia was more than doubled for both men and women with diagnosed depression. The persistent association between dementia and depression diagnosed in early and middle life suggests that depression may increase dementia risk.

Reader Response: Association Between Dietary Habits in Midlife With Dementia Incidence Over a 20-Year Period.

Glans et al.1 concluded that dietary habits in midlife were unrelated to a subsequent diagnosis of dementia. In this detailed study, dietary habits were assessed by dietary questionnaires, most of which were self-administered. The study would benefit from the measurement of biomarkers in blood samples because biomarkers are a more objective way of revealing dietary habits.

DOES THE MICROBIOME INFLUENCE THE DEVELOPMENT OF DEMENTIA IN OLDER ADULTS?

Abstract Some data implicate microbes in the pathogenesis of Alzheimer’s Disease and Related Dementias (ADRD). Whether the use of antibiotics predisposes to ADRD remains unknown. To investigate the relationship between antibiotics and subsequent cognitive function, we analyzed data from a longitudinal, nationally representative sample of older US adults (N=2,906, the National Social Life, Health and Aging Project). The use of antibiotic medications was collected by home interview at baseline. Five years later, cognition was assessed using a survey adapted version of the Montreal Cognitive Assessment (MoCA). Additionally, ADRD status was measured by a report of a physician’s diagnosis (self or proxy). The association between baseline antibiotic use and an interval dementia diagnosis/MoCA scores was tested using multivariate logistic regression, controlling for age, sex, race and ethnicity, education, co-morbidities (modified Charlson Comorbidity Index), and cognition at baseline (Short Portable Mental Status Questionnaire). Older US adults who used antibiotics had lower MoCA-SA scores at 5-year follow-up (OR=3.94, 95% CI= 1.79-8.66). However, the use of antibiotics did not predict a subsequent diagnosis of dementia (OR=1.48, 95% CI= 0.44-4.95). Thus, antibiotic use may cause deleterious effects on cognitive function, but does not appear to have a clinical impact in terms of diagnosis of dementia. Further study of the role of microbes and drugs that modulate them may be useful in understanding ADRD.

Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia: Data from pooled double-blind randomized controlled trials and nationwide disease and prescription registers.

IntroductionPeople with type 2 diabetes have increased risk of dementia. Glucagon‐like peptide‐1 (GLP‐1) receptor agonists (RAs) are among the promising therapies for repurposing as a treatment for Alzheimer's disease; a key unanswered question is whether they reduce dementia incidence in people with type 2 diabetes.MethodsWe assessed exposure to GLP‐1 RAs in patients with type 2 diabetes and subsequent diagnosis of dementia in two large data sources with long‐term follow‐up: pooled data from three randomized double‐blind placebo‐controlled cardiovascular outcome trials (15,820 patients) and a nationwide Danish registry‐based cohort (120,054 patients).ResultsDementia rate was lower both in patients randomized to GLP‐1 RAs versus placebo (hazard ratio [HR]: 0.47 (95% confidence interval [CI]: 0.25–0.86) and in the nationwide cohort (HR: 0.89; 95% CI: 0.86–0.93 with yearly increased exposure to GLP‐1 RAs).DiscussionTreatment with GLP‐1 RAs may provide a new opportunity to reduce the incidence of dementia in patients with type 2 diabetes.

Brain-age is associated with progression to dementia in memory clinic patients

BackgroundBiomarkers for the early detection of dementia risk hold promise for better disease monitoring and targeted interventions. However, most biomarker studies, particularly in neuroimaging, have analysed artificially ‘clean’ research groups, free from comorbidities, erroneous referrals, contraindications and from a narrow sociodemographic pool. Such biases mean that neuroimaging samples are often unrepresentative of the target population for dementia risk (e.g., people referred to a memory clinic), limiting the generalisation of these studies to real-world clinical settings. To facilitate better translation from research to the clinic, datasets that are more representative of dementia patient groups are warranted. MethodsWe analysed T1-weighted MRI scans from a real-world setting of patients referred to UK memory clinic services (n = 1140; 60.2 % female and mean [SD] age of 70.0[10.8] years) to derive ‘brain-age’. Brain-age is an index of age-related brain health based on quantitative analysis of structural neuroimaging, largely reflecting brain atrophy. Brain-predicted age difference (brain-PAD) was calculated as brain-age minus chronological age. We determined which patients went on to develop dementia between three months and 7.8 years after neuroimaging assessment (n = 476) using linkage to electronic health records. ResultsSurvival analysis, using Cox regression, indicated a 3 % increased risk of dementia per brain-PAD year (hazard ratio [95 % CI] = 1.03 [1.02,1.04], p < 0.0001), adjusted for baseline age, age2, sex, Mini Mental State Examination (MMSE) score and normalised brain volume. In sensitivity analyses, brain-PAD remained significant when time-to-dementia was at least 3 years (hazard ratio [95 % CI] = 1.06 [1.02, 1.09], p = 0.0006), or when baseline MMSE score ≥ 27 (hazard ratio [95 % CI] = 1.03 [1.01, 1.05], p = 0.0006). ConclusionsMemory clinic patients with older‐appearing brains are more likely to receive a subsequent dementia diagnosis. Potentially, brain-age could aid decision-making during initial memory clinic assessment to improve early detection of dementia. Even when neuroimaging assessment was more than 3 years prior to diagnosis and when cognitive functioning was not clearly impaired, brain-age still proved informative. These real-world results support the use of quantitative neuroimaging biomarkers like brain-age in memory clinics.

APOE4 Allele, Sex, and Dementia Risk in Parkinson's Disease: Lessons From a Longitudinal Cohort.

The effect of APOE4 allele on dementia risk is well established in Alzheimer's disease and Parkinson's disease (PD). However, it is unknown if sex modifies this relationship. We sought to determine the effect of sex on the relationship between APOE4 status and incident cognitive decline in PD. Data from the prospectively collected longitudinal National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) and Neuropathology Data Set (NDS) were analyzed. The NACC develops and maintains data from approximately 29 National Institutes of Aging-funded Alzheimer's Disease Research Centers. Further details may be found at the NACC web site (www.alz.washington.edu). The visit at which diagnosis of PD was made was termed the baseline visit. All patients with a PD diagnosis but without dementia at the baseline visit were included in the analyses. Presence of APOE4 allele was associated with higher odds (OR = 7.4; P < .001) of subsequent diagnosis of dementia and with a faster time to developing dementia (P = .04). Those with APOE4 allele were more likely to have neuropathology associated with Alzheimer's disease than those without APOE4 allele. We did not find any difference by sex. There were no differences between Lewy body pathology or neuron loss in the substantia nigra between the 2 groups. Sex was not associated with dementia risk in PD (OR = 0.53, P = .15) or with the time to dementia onset (P = .22). Sex did not modify the relationship between the APOE4 allele and dementia onset in PD patients (P = .12). APOE4 allele status in PD may be a predictor of cognitive decline in PD but does not appear to be modified by sex.

Predictors of New Dementia Diagnoses in Elderly Individuals: A Retrospective Cohort Study Based on Prefecture-Wide Claims Data in Japan.

Preventing dementia in elderly individuals is an important public health challenge. While early identification and modification of predictors are crucial, predictors of dementia based on routinely collected healthcare data are not fully understood. We aimed to examine potential predictors of dementia diagnosis using routinely collected claims data. In this retrospective cohort study, claims data from fiscal years 2012 (baseline) and 2016 (follow-up), recorded in an administrative claims database of the medical care system for the elderly (75 years or older) in Niigata prefecture, Japan, were used. Data on baseline characteristics including age, sex, diagnosis, and prescriptions were collected, and the relationship between subsequent new diagnoses of dementia and potential predictors was examined using multivariable logistic regression models. A total of 226,738 people without a diagnosis of dementia at baseline were followed. Of these, 26,092 incident dementia cases were detected during the study period. After adjusting for confounding factors, cerebrovascular disease (odds ratio, 1.15; 95% confidence interval, 1.11–1.18), depression (1.38; 1.31–1.44), antipsychotic use (1.40; 1.31–1.49), and hypnotic use (1.17; 1.11–1.24) were significantly associated with subsequent diagnosis of dementia. Analyses of routinely collected claims data revealed neuropsychiatric symptoms including depression, antipsychotic use, hypnotic use, and cerebrovascular disease to be predictors of new dementia diagnoses.

The association of depression with subsequent dementia diagnosis: A Swedish nationwide cohort study from 1964 to 2016.

Depression is associated with an increased risk of dementia. However, short follow-up times and lack of adjustment for familial factors in previous studies could influence this association. The purpose of the present study was to investigate the association between depression and subsequent dementia, while controlling for familial factors and with a follow-up of over 35 years. Two cohorts were formed from all individuals aged 50 years or older living in Sweden as of 31 December 2005 (n = 3,341,010). The Swedish National Patient Register was searched from 1964 through 2016 to identify diagnosis of depression and dementia. In the first cohort, individuals diagnosed with depression (n = 119,386) were matched 1:1 with controls without depression diagnosis. The second cohort was a sibling cohort (n = 50,644) consisting of same-sex full sibling pairs with discordant depression status. In the population matched cohort study, a total of 9,802 individuals were diagnosed with dementia during a mean follow-up time of 10.41 (range 0-35) years (5.5% of those diagnosed with depression and 2.6% of those without depression diagnosis (adjusted odds ratio [aOR] 2.47, 95% CI 2.35-2.58; p < 0.001), with a stronger association for vascular dementia (aOR 2.68, 95% CI 2.44-2.95; p < 0.001) than for Alzheimer disease (aOR 1.79, 95% CI 1.68-1.92; p < 0.001). The association with dementia diagnosis was strongest in the first 6 months after depression diagnosis (aOR 15.20, 95% CI 11.85-19.50; p < 0.001), then decreased rapidly but persisted over follow-up of more than 20 years (aOR 1.58, 95% CI 1.27-1.98; p < 0.001). Also in the sibling cohort, the association was strongest in the first 6 months (aOR 20.85, 95% CI 9.63-45.12; p < 0.001), then decreased rapidly but persisted over follow-up of more than 20 years (aOR 2.33, 95% CI 1.32-4.11; p < 0.001). The adjusted models included sex, age at baseline, citizenship, civil status, household income, and diagnoses at baseline. The main limitation of the study methodology is the use of observational data; hence, the associations found are not proof of causal effects. Depression is associated with increased odds of dementia, even more than 20 years after diagnosis of depression, and the association remains after adjustment for familial factors. Further research is needed to investigate whether successful prevention and treatment of depression decrease the risk of dementia.

Predicting Dementia in Cerebral Small Vessel Disease Using an Automatic Diffusion Tensor Image Segmentation Technique.

Background and Purpose- Cerebral small vessel disease (SVD) is the most common cause of vascular cognitive impairment, with a significant proportion of cases going on to develop dementia. We explore the extent to which diffusion tensor image segmentation technique (DSEG; which characterizes microstructural damage across the cerebrum) predicts both degree of cognitive decline and conversion to dementia, and hence may provide a useful prognostic procedure. Methods- Ninety-nine SVD patients (aged 43-89 years) underwent annual magnetic resonance imaging scanning (for 3 years) and cognitive assessment (for 5 years). DSEG-θ was used as a whole-cerebrum measure of SVD severity. Dementia diagnosis was based Diagnostic and Statistical Manual of Mental Disorders V criteria. Cox regression identified which DSEG measures and vascular risk factors were related to increased risk of dementia. Linear discriminant analysis was used to classify groups of stable versus subsequent dementia diagnosis individuals. Results- DSEG-θ was significantly related to decline in executive function and global cognition (P<0.001). Eighteen (18.2%) patients converted to dementia. Baseline DSEG-θ predicted dementia with a balanced classification rate=75.95% and area under the receiver operating characteristic curve=0.839. The best classification model included baseline DSEG-θ, change in DSEG-θ, age, sex, and premorbid intelligence quotient (balanced classification rate of 79.65%; area under the receiver operating characteristic curve=0.903). Conclusions- DSEG is a fully automatic technique that provides an accurate method for assessing brain microstructural damage in SVD from a single imaging modality (diffusion tensor imaging). DSEG-θ is an important tool in identifying SVD patients at increased risk of developing dementia and has potential as a clinical marker of SVD severity.

Long-term risk of dementia after acute respiratory failure requiring intensive care unit admission.

This retrospective, population-based cohort study aims to investigate the long-term risk of newly diagnosed dementia in patients discharged for acute respiratory failure that required mechanical ventilation (MV) and intensive care unit (ICU) admission. From the Taiwan National Health Insurance Research Database, first-time ICU patients using MV between June 1, 1998, and December 31, 2012, were enrolled, and they were followed-up until the earliest onset of one of our two endpoints: a new diagnosis of dementia (primary endpoint), or the end of the study. A total of 18,033 patients were enrolled and thirteen hundred eighty-seven patients had been newly diagnosed with dementia (mean onset: 3.2 years post-discharge). Patients ≥ 85 years old had the highest risk (multivariate analysis). Males had a lower risk than did females in both models (HR: 0.81, 95% CI: 0.72–0.9 in model 1; HR: 0.80, 95% CI: 0.72–0.89 in model 2). ICU stays > 5 days, hospital stays > 14 days, and more ICU readmissions were associated with a higher risk of developing dementia. In conclusion, the long-term risks of a subsequent diagnosis of dementia for acute respiratory failure with MV patients who survive to discharge increase with age and are higher in women than in men. Additionally, the longer the ICU or hospital stay is, and the more ICU readmissions a patient has, are both significantly associated with developing dementia.

Association between different anticholinergic drugs and subsequent dementia risk in patients with diabetes mellitus.

BackgroundThe effects of oxybutynin, solifenacin and tolterodine on dementia risk in patients with diabetes mellitus (DM) remain unknown. We investigated the effects of oxybutynin, solifenacin and tolterodine on dementia risk in patients with DM.MethodsWe conducted a cohort study by using the diabetes dataset of the Taiwan National Health Insurance Research Database from 1 January, 2002 to 31 December, 2013. We included 10,938 patients received one type of oxybutynin, solifenacin, or tolterodine, while 564,733 had not. We included a comparable number of patients not receiving oxybutynin, solifenacin, or tolterodine as controls through systematic random sampling matching by age, gender, and the year of the index date with 1 to 1 ratio. The dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors.ResultsThe dementia event rates were 3.9% in the oxybutynin group, 4.3% in the solifenacin group, 2.2% in the tolterodine group and 1.2% in the control group (P<0.001). The adjusted HRs compared to nonusers of anticholinergic drugs were 2.35 (95% CI, 1.96 to 2.81), 2.16 (95% CI, 1.81 to 2.58), and 2.24 (95% CI, 1.85 to 2.73), respectively, for patients receiving oxybutynin, solifenacin, or tolterodine.ConclusionOur study indicates an association between taking oxybutynin, solifenacin and tolterodine and the subsequent diagnosis of dementia in DM patients. Moreover, the patients using oxybutynin had highest risk. The impact of these three drugs on risk of dementia in non-diabetic populations is warrant.

Cognitive impairment and Charles Bonnet syndrome: a prospective study.

Charles Bonnet syndrome (CBS) is a common cause of visual hallucinations in older people. The relationship between CBS and cognitive impairment is unclear, but anecdotal reports exist of dementia emerging in patients diagnosed with CBS. This work set out to determine if there is an increased incidence of dementia, and increased severity of cognitive impairment, in people with CBS compared to controls from the same clinical setting. People over 65 attending low-vision and glaucoma clinics, and a cohort of age-matched controls, underwent a psychiatric assessment. The cohorts were followed up after one year. Mild cognitive impairment was present in 2/12 CBS participants and 2/10 controls. Partial insight was seen in nine CBS participants. Two participants with CBS, and no controls, developed dementia at follow-up. No significant differences in performance on the ACE-R were found between the groups. Both participants who developed dementia had partial insight and hallucinations of familiar figures at diagnosis of CBS, and one had mild cognitive impairment. Reassurance that CBS is universally benign may be misplaced. Some people given this diagnosis go on to develop dementia. Cognitive testing at the point of diagnosis was unable to identify those at risk of this outcome. Partial insight, the presence of Mild Cognitive Impairment, and hallucinations of familiar figures at diagnosis of CBS may confer an increased risk of subsequent dementia diagnosis. Copyright © 2017 John Wiley & Sons, Ltd.

Risk of dementia in patients with celiac disease: a population-based cohort study.

Patients with celiac disease (CD) frequently report cognitive symptoms when they are exposed to gluten, and cognitive deficits have been quantified in patients with newly diagnosed CD. To determine whether patients with CD have an increased risk of dementia. Using a population-based database of older adults (age ≥50 years) with histologically proven CD (duodenal/jejunal villous atrophy) from all 28 pathology departments in Sweden, we compared the incidence of a subsequent dementia diagnosis to those of age- and gender-matched controls. Among patients with CD (n = 8,846) and controls (n = 43,474), the median age was 63 years and 56% were female. During a median follow-up time of 8.4 years, dementia was diagnosed in 4.3% of CD patients and 4.4% of controls (HR 1.07; 95% CI 0.95-1.20). Although there was an increased risk of dementia in the first year following a diagnosis of CD (HR 1.73; 95% CI 1.15-2.61), this risk was not present in the whole observation period. Among those subjects with a dementia subtype specified, the increased risk was restricted to vascular dementia (HR 1.28; 95% CI 1.00-1.64) and was not present for Alzheimer's dementia (HR 1.12; 95% CI 0.91-1.37). Patients with CD are not at increased risk for dementia overall, though subgroup analysis suggests that they may be at increased risk for vascular dementia.

Incidence of dementia in relation to genetic variants at PITX2, ZFHX3, and ApoE ε4 in atrial fibrillation patients.

Mechanisms underlying atrial fibrillation (AF) and dementia are unknown. Some genetic risk factors convey risk for AF and cerebral ischemic events. These markers may identify AF patients at risk for dementia either directly or through a gene-gene interaction with the ApoE ε4 variant, a known marker of dementia risk. Caucasian patients with AF and a subsequent dementia diagnosis (n = 112) were matched 1:2 on sex, AF onset age, and follow-up period to AF patients without dementia. AF patients with dementia and AF patients without dementia were matched 1:1 on sex and age at dementia diagnosis (n = 112). Genotyping employed Taqman real-time polymerase chain reaction. Multivariable conditional logistic regression was used to examine associations between AF/dementia groups and single nucleotide polymorphism (SNP), as well as gene-gene interactions. In dementia patients, there was an association between the PITX2 loci and AF (rs2634073: odds ratio [OR] = 2.11; P = 0.025 and rs2200733: OR = 2.27; P = 0.029). In patients with AF, there was an association between PITX2 loci, rs2200733, and dementia (OR = 2.15, P = 0.008). There was no association between ApoE ε4 allele and AF in patients with dementia, although confirmation of the association between the carriage of ApoE ε4 allele and dementia was found (OR = 1.79; P = 0.026) in patients with AF. There were no significant interactions between ApoE ε4 allele and both the PITX2 loci and ZFHX3. These findings support prior studies of ApoE risk of noncerebral vascular accident-related dementia/Alzheimer's risk in the Caucasians and provide support to suggest an association between PITX2-related SNPs and dementia, which may in part be attributed to silent cerebral ischemic events, a hypothesis deserving further testing.

Subjective memory complaints in general practice predicts future dementia: a 4‐year follow‐up study

Many older patients in general practice have subjective memory complaints (SMC); however, not all share this information with their general practitioner (GP). The association between SMC and future cognitive decline or dementia is not clear, especially in a general practice population. The aim of this study was to determine the risk for receiving a subsequent hospital-based dementia diagnosis on the basis of patients' reports of SMC in a primary care setting. Prospective cohort survey with 4-year register-based follow-up in general practice. All 17 practices with a total of 24 GPs working in the inner district of Copenhagen municipality, Denmark. A total of 40 865 patients were listed, and 2934 were 65 years or older. Cox proportional hazard models were used to examine the influence of risk factors for hospital-based dementia diagnosis. A total of 758 non-nursing home residents aged 65 years and older consulted their GP in October and November 2002, and, when asked, 177 (24%) reported memory problems, and 50 (6.6%) received a hospital-based dementia diagnosis within the 4-years follow-up. SMC had an adjusted Hazard Ratio (HR) of 2.27 for subsequent dementia diagnosis. Other statistical significant covariates were Mini Mental State Examination < 24 (HR 3.97), age (HR 2.73 for 75-84 years and HR 3.75 for 85+ years) and receiving home care (HR 3.24) This study indicates that the presence of SMC in an older general practice population is a significant independent predictor for subsequent hospital-based dementia diagnosis. Thus, the GP could consider inquiring for memory complaints to identify vulnerable older patients.