Higher Incidence Of Dementia Research Articles

A Post-hoc Study of D-Amino Acid Oxidase in Blood as an Indicator of Post-stroke Dementia.

Stroke is an important risk factor for dementia. Epidemiological studies have indicated a high incidence of dementia in stroke patients. There is currently no effective biomarker for the diagnosis of post-stroke dementia (PSD). D-amino acid oxidase (DAO) is a flavin-dependent enzyme widely distributed in the central nervous system. DAO oxidizes D-amino acids, a process which generates neurotoxic hydrogen peroxide and leads to neurodegeneration. This study aimed to examine post-stroke plasma DAO levels as a biomarker for PSD. In total, 53 patients with PSD, 20 post-stroke patients without dementia (PSNoD), and 71 age- and gender-matched normal controls were recruited. Cognitive function was evaluated at more than 30 days post-stroke. Plasma DAO was measured using the enzyme-linked immunosorbent assay. White matter hyperintensity (WMH), a neuroimaging biomarker of cerebral small vessel diseases, was determined by magnetic resonance imaging. We found that plasma DAO levels were independently higher in PSD subjects than in PSNoD subjects or the controls and were correlated with the WMH load in stroke patients. Using an area under the curve (AUC)/receiver operating characteristic analysis, plasma DAO levels were significantly reliable for the diagnosis of PSD. The sensitivity and specificity of the optimal cut-off value of 321 ng/ml of plasma DAO for the diagnosis of PSD were 75 and 88.7%, respectively. In conclusion, our data support that plasma DAO levels were increased in PSD patients and correlated with brain WMH, independent of age, gender, hypertension, and renal function. Plasma DAO levels may therefore aid in PSD diagnosis.

Risk Aversion and Alzheimer Disease in Old Age

To test the hypothesis that late-life risk aversion is partly a prodromal sign of dementia. The authors' design was a longitudinal clinical-pathologic cohort study. The setting included participants' residences in the Chicago area, and a total of 874 older persons without dementia were enrolled. At baseline, risk aversion was assessed with questions involving choices between certain smaller rewards and uncertain larger rewards. At annual intervals thereafter, participants underwent evaluations that included cognitive testing and diagnosis of mild cognitive impairment (MCI) and dementia. At death, a neuropathologic examination was done to quantify common pathologies linked to dementia. Risk aversion at study onset ranged from 0.05-0.91 (mean: 0.32, standard deviation: 0.31). During a mean of 4.6 years of follow-up, 123 (of 874) developed dementia. Higher risk aversion was associated with higher dementia incidence (hazard ratio [HR]: 2.08; 95% confidence interval: 1.18, 3.65) and more rapid decline in episodic (estimate: -0.062; standard error [SE]: 0.019; t [3677]: -3.33; p < 0.001) and semantic (estimate: -0.039; SE: 0.015; t [3655]: -2.61; p = 0.009) memory but not in other cognitive systems. Of 702 people without cognitive impairment at baseline, 223 developed incident MCI. Higher risk aversion was associated with higher incidence of MCI (HR: 2.10; 95% confidence interval: 1.34, 3.29) and more rapid episodic memory decline. In 181 neuropathologically examined individuals, higher risk aversion was associated with higher levels of plaques, tangles, and cerebral amyloid angiopathy. The results support the hypothesis that high risk aversion in old age is partly an early sign of the pathology of Alzheimer disease.

Depressive Symptoms Predict Incident Dementia in a Community Sample of Older Adults: Results From the Einstein Aging Study.

There is increasing evidence that depressive symptoms are associated with increased risk of cognitive impairment and dementia in older adults. In current study, we aimed to investigate the effect of depressive symptoms on incident Alzheimer disease and all-cause dementia in a community sample of older adults. Participants were 1219 older adults from the Einstein Aging Study, a longitudinal cohort study of community-dwelling older adults in Bronx County, New York. The Geriatric Depression Scale (GDS, 15-item) was used as a measure of depressive symptoms. The primary outcome was incident dementia diagnosed using the Diagnostic and Statistical Manual, Fourth Edition, criteria. Cox proportional hazard models were used to estimate the risk of incident dementia as a function of GDS score for the whole population and also for 2 different time intervals, <3 years and ≥3 years after baseline assessment. Among participants, 132 individuals developed dementia over an average 4.5 years (standard deviation [SD] = 3.5) of follow-up. Participants had an average age of 78.3 (SD = 5.4) at baseline, and 62% were women. Among all participants, after controlling for demographic variables and medical comorbidities, a 1-point increase in GDS was associated with higher incidence of dementia (hazard ratio [HR] = 1.11, P = .007). After up to 3 years of follow-up, depressive symptoms were not significantly associated with dementia incidence (HR = 1.09; P = .070). However, after more than 3 years, GDS score was a significant predictor of incident dementia (HR = 1.13, P = .028). Our results suggest that depressive symptoms are associated with an increased risk of incident dementia in older adults.

Tamsulosin and Dementia in old age: is there any relationship?

Tamsulosin is used to treat Benign Prostatic Hyperplasia (BPH), prescribed annually to about 12.6 million patients worldwide. It is an alpha-adrenergic antagonist that reduces the tone of the prostate smooth muscle involved in the pathophysiology of BPH. By acting on alpha 1A receptors, predominant in the prostate, tamsulosin also acts on receptors present in the brain. This study consisted of a literature review aimed at disseminating scientific knowledge about the relationship between the use of tamsulosin and the onset of dementia. Pubmed, Scopus, Scielo, Embase, and Web of Science studies involving dementia in patients using tamsulosin in the last five years were selected. The review showed a risk correlation and a higher incidence of dementia in treated patients. The risk ratio, when compared to other medicines, approached 1.20. In conclusion, it was identified the need for clinical trials with higher sampling power to increase relational significance due to the high prevalence of BPH and the extensive use of tamsulosin in elderly patients with the disease.

Tooth loss as a risk factor for dementia: systematic review and meta-analysis of 21 observational studies

BackgroundTooth loss is suggested to be associated with an increased risk of dementia in many studies. But the relationship between tooth loss and dementia is not yet fully understood. This systematic review and meta-analysis aimed to determine the relative effect of tooth loss on dementia risk.MethodsAn electronic search of PubMed, Scopus, Embase, and Web of Knowledge was conducted in March 2018 to identify relevant observational studies with the English language restriction. Studies were included if they assessed the relationship between tooth loss and risk of dementia. Study quality was detected by the modified Downs and Black scale. Odds risks (ORs) were pooled using a random-effects model in the crude model.ResultsThe literature search initially yielded 1574 articles, and 21 observational studies published between 1994 and 2017 were finally included for the analyses. The crude results with random-effects model showed that patients with multiple tooth loss had higher incidence of dementia (OR 2.62, 95% CI 1.90–3.61, P < 0.001, I2 = 90.40%). The association remained noted when only adjusted results were pooled from 18 studies (OR 1.55, 95% CI 1.41–1.70, P = 0.13, I2 = 28.00%). Meta-regression analysis showed that study design explained about 16.52% of heterogeneity in the crude model. The overall quality rating scores of studies ranged from 11 to 16.ConclusionsFindings from this review evidenced that tooth loss is positively associated with an increased risk of dementia in adults. Future well-designed longitudinal researches examining the direct and indirect relationship between tooth loss and dementia risk are encouraged.

Comparison of CHA2DS2-VASc and AHEAD scores for the prediction of incident dementia in patients hospitalized for heart failure: a nationwide cohort study.

This study explores the use of the CHA2DS2-VASc and the AHEAD scores to predict incident dementia in patients with heart failure (HF) who need hospitalization. We used a large national database to study 387,595 adult patients hospitalized for HF from Taiwan. This registration cohort was followed to document the cumulative incidence of dementia. The area under the curve of receiver operating characteristics (AUROC) was used to evaluate the discriminative ability of CHA2DS2-VASc and AHEAD scores in predicting dementia, whereas the DeLong test was used to examine the difference between the predictive capacity. A higher CHA2DS2-VASc and AHEAD scores appear to be more strongly associated with a higher incidence of dementia. The AUROC for CHA2DS2-VASc score in predicting dementia (0.61, 95% CI = 0.60-0.61) is significantly higher than the AHEAD score (0.55, 95% CI = 0.54-0.55) (DeLong test p < 0.001). A significantly higher ability, by AUROC, of CHA2DS2-VASc score to predict new-onset dementia in patients hospitalized for HF is found.

Shift work and risk of incident dementia: a study of two population-based cohorts

This study aimed to investigate the association between shift work and incident dementia in two population-based cohorts from the Swedish Twin Registry (STR). The STR-1973 sample included 13,283 participants born 1926–1943 who received a mailed questionnaire in 1973 that asked about status (ever/never) and duration (years) of shift work employment. The Screening Across the Lifespan Twin (SALT) sample included 41,199 participants born 1900–1958 who participated in a telephone interview in 1998–2002 that asked about night work status and duration. Dementia diagnoses came from Swedish patient registers. Cox proportional-hazards regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Potential confounders such as age, sex, education, diabetes, cardiovascular disease and stroke were included in adjusted models. In genotyped subsamples (n = 2977 in STR-1973; n = 10,366 in SALT), APOE ε4 status was considered in models. A total of 983 (7.4%) and 1979 (4.8%) dementia cases were identified after a median of 41.2 and 14.1 years follow-up in the STR-1973 and SALT sample, respectively. Ever shift work (HR 1.36, 95% CI 1.15–1.60) and night work (HR 1.12, 95% CI 1.01–1.23) were associated with higher dementia incidence. Modest dose-response associations were observed, where longer duration shift work and night work predicted increased dementia risk. Among APOE ε4 carriers, individuals exposed to ≥ 20 years of shift work and night work had increased dementia risk compared to day workers. Findings indicate that shift work, including night shift work, compared to non-shift jobs is associated with increased dementia incidence. Confirmation of findings is needed.

Depression in Parkinson's disease: A case-control study

BackgroundTo evaluate the association between Parkinson’s disease (PD) prognosis and the patient’s onset of depression.MethodsA total of 353 patients with newly-diagnosed PD and a history of depression were enrolled. On the basis of the onset of depression before or after PD diagnosis, we divided participants into PD patients with pre- or post-diagnostic depression. Cox’s regression analysis was used to detect risks between the onset of depression and outcomes (including death, accidental injury, dementia, and aspiration pneumonia). The association between the onset of depression and levodopa equivalent dosage (LED) and cumulative equivalent dosage of antidepressants were assessed.ResultsPD patients with post-diagnostic depression were associated with significantly higher risks of dementia (adjusted HR = 2·01, p = 0·015), and were older (58·5 ± 17·7 vs. 53·7 ± 18·6, p = 0·020) at the time of PD diagnosis than PD patients with pre-diagnostic depression. The higher incident rate of accidental injury was also noted in PD patients with post-diagnostic depression (48·1 vs. 31·3/1000 person-years, HR = 1·60, p = 0·041), but no statistical significance was observed in the adjusted hazard ratio (HR) (HR = 1·52, p = 0·069). Otherwise, mortality, motor condition and severity of depression revealed no significant difference between PD patients with pre-diagnostic and post-diagnostic depression.ConclusionPD patients with post-diagnostic depression had higher incidence of dementia, implying different onset time of depression could be associated with different subtypes and spreading routes which should be examined in follow-up studies.

Vitamin D and the Risk of Dementia: TheRotterdam Study.

Vitamin D has gained interest as a potentially modifiable risk factor for dementia because of its putative neuroprotective effects. However, longitudinal studies examining the association between vitamin D and dementia have provided inconsistent results. To determine the relationship of serum vitamin D with prevalent and incident dementia in the general population. Within the prospective Rotterdam Study, we measured serum 25-hydroxyvitamin D concentrations between 1997 and 2001 using electrochemiluminescence-immunoassay in 6220 participants 55 years or older. We assessed dementia at baseline and continuously during follow-up until 1 January 2015. We used appropriate regression models to determine the relationship of vitamin D with prevalent and incident dementia, including Alzheimer's disease (AD). We adjusted models for age, sex, and season of blood collection. Additionally, we adjusted for ethnicity, education, cardiovascular risk factors, serum calcium, kidney function, depression, outdoor-activity and APOEɛ4 carriership. At baseline, 127 of 6,220 participants had dementia, of whom 97 had AD. Lower vitamin D concentrations were associated with a non-significantly higher prevalence of dementia (adjusted OR, per SD decrease 1.20, 95% CI 0.95;1.52), but not with AD (adjusted OR: 0.97, 95% CI 0.74;1.29). Among 6,087 non-demented participants with 68,884 person-years of follow-up, 795 participants developed dementia, of whom 641 had AD. Lower vitamin D concentrations were associated with higher risk of dementia (adjusted HR, per SD decrease 1.11, 95% CI 1.02;1.20) and AD (adjusted HR: 1.13, 95% CI 1.03;1.24). Lower serum vitamin D concentrations are associated with a higher incidence of dementia.

Exposure to ambient air pollution and the incidence of dementia: A population-based cohort study

IntroductionEmerging studies have implicated air pollution in the neurodegenerative processes. Less is known about the influence of air pollution, especially at the relatively low levels, on developing dementia. We conducted a population-based cohort study in Ontario, Canada, where the concentrations of pollutants are among the lowest in the world, to assess whether air pollution exposure is associated with incident dementia. MethodsThe study population comprised all Ontario residents who, on 1 April 2001, were 55–85years old, Canadian-born, and free of physician-diagnosed dementia (~2.1 million individuals). Follow-up extended until 2013. We used population-based health administrative databases with a validated algorithm to ascertain incident diagnosis of dementia as well as prevalent cases. Using satellite observations, land-use regression model, and an optimal interpolation method, we derived long-term average exposure to fine particulate matter (≤2.5μm in diameter) (PM2.5), nitrogen dioxide (NO2), and ozone (O3), respectively at the subjects' historical residences based on a population-based registry. We used multilevel spatial random-effects Cox proportional hazards models, adjusting for individual and contextual factors, such as diabetes, brain injury, and neighborhood income. We conducted various sensitivity analyses, such as lagging exposure up to 10years and considering a negative control outcome for which no (or weaker) association with air pollution is expected. ResultsWe identified 257,816 incident cases of dementia in 2001–2013. We found a positive association between PM2.5 and dementia incidence, with a hazard ratio (HR) of 1.04 (95% confidence interval (CI): 1.03–1.05) for every interquartile-range increase in exposure to PM2.5. Similarly, NO2 was associated with increased incidence of dementia (HR=1.10; 95% CI: 1.08–1.12). No association was found for O3. These associations were robust to all sensitivity analyses examined. These estimates translate to 6.1% of dementia cases (or 15,813 cases) attributable to PM2.5 and NO2, based on the observed distribution of exposure relative to the lowest quartile in concentrations in this cohort. DiscussionIn this large cohort, exposure to air pollution, even at the relative low levels, was associated with higher dementia incidence.

Hearing loss as a risk factor for dementia: A systematic review.

ObjectivesTo review evidence of hearing loss as a risk factor for dementia. Data Sources: PubMed Review methods: A systematic review was conducted using the PubMed database using the search terms (hearing loss OR presbycusis) AND (dementia OR cognitive decline). Initially, 488 articles were obtained. Only those studies evaluating an association between hearing loss and incident dementia or cognitive decline were included in the analysis. This resulted in 17 articles which were thoroughly evaluated with consideration for study design, method for determining hearing loss and cognitive status, relevant covariates and confounding factors, and key findings.ResultsAll of the 17 articles meeting inclusion criteria indicate that hearing loss is associated with dementia or cognitive decline. The methods used among the studies for ascertaining hearing loss and dementia were notably varied. For hearing loss, peripheral auditory function was tested far more than central auditory function. For peripheral audition, pure tone audiometry was the most commonly reported method for defining hearing loss. Only a few studies measured central auditory function by using the Synthetic Sentence Identification with Ipsilateral Competing Message test (SSI‐ICM) and the Staggered Spondaic Word Test (SSW). Dementia was most often defined using the Mini Mental State Exam (MMSE). However, many studies used extensive batteries of tests to define cognitive status, often including a neuropsychologist. Confounding variables such as cardiovascular risk factors were measured in 17 studies and family history of dementia was only evaluated in 1 study. Overall, the methods used by studies to ascertain hearing loss, cognitive status and other variables are valid, making their evaluation appear reliable.ConclusionWhile each of the studies included in this study utilized slightly different methods for evaluating participants, each of them demonstrated that hearing loss is associated with higher incidence of dementia in older adults.Level of EvidenceLevel V, systematic review.

Living near major roads and the incidence of dementia, Parkinson's disease, and multiple sclerosis: a population-based cohort study

Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinson's disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada. In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20-50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55-85 years (about 2·2 million; dementia or Parkinson's disease cohort) who resided in Ontario, Canada on April 1, 2001. Eligible patients were free of these neurological diseases, Ontario residents for 5 years or longer, and Canadian-born. We ascertained the individual's proximity to major roadways based on their residential postal-code address in 1996, 5 years before cohort inception. Incident diagnoses of dementia, Parkinson's disease, and multiple sclerosis were ascertained from provincial health administrative databases with validated algorithms. We assessed the associations between traffic proximity and incident dementia, Parkinson's disease, and multiple sclerosis using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighbourhood income. We did various sensitivity analyses, such as adjusting for access to neurologists and exposure to selected air pollutants, and restricting to never movers and urban dwellers. Between 2001, and 2012, we identified 243 611 incident cases of dementia, 31 577 cases of Parkinson's disease, and 9247 cases of multiple sclerosis. The adjusted hazard ratio (HR) of incident dementia was 1·07 for people living less than 50 m from a major traffic road (95% CI 1·06-1·08), 1·04 (1·02-1·05) for 50-100 m, 1·02 (1·01-1·03) for 101-200 m, and 1·00 (0·99-1·01) for 201-300 m versus further than 300 m (p for trend=0·0349). The associations were robust to sensitivity analyses and seemed stronger among urban residents, especially those who lived in major cities (HR 1·12, 95% CI 1·10-1·14 for people living <50 m from a major traffic road), and who never moved (1·12, 1·10-1·14 for people living <50 m from a major traffic road). No association was found with Parkinson's disease or multiple sclerosis. In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia, but not with Parkinson's disease or multiple sclerosis. Health Canada (MOA-4500314182).

Is Stroke a Neurodegenerative Condition? A Critical Review of Secondary Neurodegeneration and Amyloid-beta Accumulation after Stroke

Stroke-induced secondary neurodegeneration (SND) refers to the progressive and inexorable loss of tissues at sites connected to area damaged by the initial infarction. SND has been consistently observed to occur in humans and rodents after stroke. Intriguingly, stroke-induced SND shares a number of striking similarities to other neurodegenerative diseases such as Alzheimer’s disease, most notably with respect to the significant accumulation of the neurotoxic protein amyloid-β. Together, this observation and others (progressive neuronal loss and neuroinflammation) suggest the possibility that stroke may induce a neurodegenerative condition. Certainly, this is supported to some degree by the relatively high incidence of dementia after stroke. We begin this review by addressing the available research on human and rodent SND pathology after stroke. We next consider amyloid-β in the context of SND. We discuss what amyloid-β is, how is it made, and introduce some caveats on how amyloid-β measurements should be interpreted. In summary, we conclude that there is now robust pre-clinical evidence demonstrating the presence of amyloid disturbances at sites of SND after stroke. We find, however, that the human literature on the topic is more limited and further work is warranted. While the understanding of amyloid disturbances remains inconclusive in human studies, stroke clearly lead to the development of a neurodegenerative-like condition at the sites of SND, with prominent features such as death of neurons and gliosis.

Association Between Sleep Characteristics and Incident Dementia Accounting for Baseline Cognitive Status: A Prospective Population-Based Study.

Although research has shown that sleep disorders are prevalent among people with dementia, the temporal relationship is unclear. We investigated whether atypical sleep characteristics were associated with incident dementia while accounting for baseline cognitive functioning. Screening Across the Lifespan Twin (SALT) study participants were 11,247 individuals from the Swedish Twin Registry who were at least 65 years at baseline (1998-2002). Sleep and baseline cognitive functioning were assessed via the SALT telephone screening interview. Data on dementia diagnoses came from national health registers. Cox regression was performed to estimate hazard ratios for dementia. After 17 years of follow-up, 1,850 dementia cases were identified. Short (≤6 hours) and extended (>9 hours) time in bed (TIB) compared to the middle reference group (hazard ratio = 1.40, 95% confidence interval = 1.06-1.85; hazard ratio = 1.11, 95% confidence interval = 1.00-1.24, respectively) and rising at 8:00 AM or later compared to earlier rising (hazard ratio = 1.12, 95% confidence interval = 1.01-1.24) were associated with higher dementia incidence. Bedtime, sleep quality, restorative sleep, and heavy snoring were not significant predictors. Findings stratified by baseline cognitive status indicated that the association between short TIB and dementia remained in those cognitively intact at the start. Short and extended TIB and delayed rising among older adults predicted increased dementia incidence in the following 17 years. The pattern of findings suggests that extended TIB and late rising represent prodromal features whereas short TIB appeared to be a risk factor for dementia.

Dissociation of Down syndrome and Alzheimer's disease effects with imaging

IntroductionDown Syndrome (DS) adults experience accumulation of Alzheimer's disease (AD)–like amyloid plaques and tangles and a high incidence of dementia and could provide an enriched population to study AD-targeted treatments. However, to evaluate effects of therapeutic intervention, it is necessary to dissociate the contributions of DS and AD from overall phenotype. Imaging biomarkers offer the potential to characterize and stratify patients who will worsen clinically but have yielded mixed findings in DS subjects. MethodsWe evaluated 18F fluorodeoxyglucose positron emission tomography (PET), florbetapir PET, and structural magnetic resonance (sMR) image data from 12 nondemented DS adults using advanced multivariate machine learning methods. ResultsOur results showed distinctive patterns of glucose metabolism and brain volume enabling dissociation of DS and AD effects. AD-like pattern expression corresponded to amyloid burden and clinical measures. DiscussionThese findings lay groundwork to enable AD clinical trials with characterization and disease-specific tracking of DS adults.

Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia

Vascular risk factors are associated with a higher incidence of dementia. Diabetes mellitus is considered as a main risk factor for Alzheimer's disease and vascular dementia. Both forms of dementia are posing greater risk to the world population and are increasing at a faster rate. In the past we have reported the induction of vascular dementia by experimental diabetes. This study investigates the role of vildagliptin, a dipeptidyl peptidase-4 inhibitor in the pharmacological interdiction of pancreatectomy diabetes induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. Pancreatectomy diabetes rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with increase in brain inflammation, oxidative stress and calcium. Administration of vildagliptin has significantly attenuated pancreatectomy induced impairment of learning, memory, endothelial function, blood brain barrier permeability and biochemical parameters. It may be concluded that vildagliptin, a dipeptidyl peptidase-4 inhibitor may be considered as potential pharmacological agents for the management of pancreatectomy induced endothelial dysfunction and subsequent vascular dementia. The selective modulators of dipeptidyl peptidase-4 may further be explored for their possible benefits in vascular dementia.

Childhood and Adulthood Rural Residence Increases the Risk of Dementia: NEDICES Study.

This research aims to determine whether residence (rural vs. urban) at different life stages (childhood, adulthood, and late life) is associated with increased risk of incident dementia in a population-based cohort of older Spaniards. In this prospective study, 2,711 participants aged 65 years and older were assessed at baseline and 3 years later. All cases of incident dementia were diagnosed using DSM-IV criteria. The relationship between residence and the relative risk of dementia was analysed using Cox's regression models. Demographics, comorbidity index, consumption (tobacco / alcohol) and doubtful dementia diagnosis were considered as possible confounders. At the three-year follow-up, 91 cases of dementia were detected. Lower education and occupational attainment were associated with a higher incidence of dementia three years later. Rural residence in adulthood was associated with a significantly higher risk of dementia at the follow-up. Childhood rural residence revealed a marked trend for risk of dementia (p = 0.08), but it was nonsignificant in later life. The risk of dementia was considerably higher for the rural/low-education group than for the urban/high-education group, for both childhood and adulthood residence. Finally, people from areas with the lowest socio- economic status Arévalo (rural, blue-collar) and Margaritas (urban, blue-collar) showed higher risk of dementia than people from Lista (urban, mixed white/blue collar). In this cohort, early and mid-life stages rural residence was a risk factor for dementia, but not later-life rural residence. The rural residence effect was noticeably higher in people with a lower educational level.

Stroke suggests increased risk of dementia.

Stroke is a major cause of disability in the elderly and considerably increases the risk of dementia, which is another important source of disability. This population-based study aimed to examine the risk of dementia in patients with stroke compared with non-stroke cases with similar comorbidities. Using the Taiwan National Health Insurance databank covering the period 2001-2007, this retrospective cohort study evaluated the risk of dementia in 10,884 patients with first stroke who had no history of dementia. In this study, we performed a 1:5 case-control matched analysis, in which cases were matched to controls based on their estimated propensity scores, which were estimated with demographics and associated risk factors. This approach reduced selection bias. Cox proportional hazards regression analysis was then used to estimate the risk of dementia in stroke patients. During the 5-year follow-up period, 1,487 (13.74%) stroke and 1,402 (2.59%) non-stroke patients suffered dementia. Stroke was independently associated with a 6.09 (95% confidence interval [CI], 5.66 to 6.55) times greater risk of dementia 5 years after stroke. Older age was associated with a higher incidence of dementia after stroke. Each stroke type had different impacts on the occurrence of dementia. The hazard ratio of dementia among hemorrhagic stroke patients was much higher than those of ischemic stroke and controls. The findings of this study suggest that stroke confers an increased risk of dementia, especially in the elderly and in patients with hemorrhagic stroke. We advocate the need for close observation and enhanced health education programs to benefit patients with stroke.

Type 2 diabetes aggravates Alzheimer's disease-associated vascular alterations of the aorta in mice.

Vascular risk factors are associated with a higher incidence of dementia. In fact, diabetes mellitus is considered a main risk factor for Alzheimer's disease (AD) and both diseases are characterized by vascular dysfunction. However, the underlying mechanisms remain largely unknown. Here, the effects of high-sucrose-induced type 2 diabetes (T2D) in the aorta of wild type (WT) and triple-transgenic AD (3xTg-AD) mice were investigated. 3xTg-AD mice showed a significant decrease in body weight and an increase in postprandial glycemia, glycated hemoglobin (HbA1c), and vascular nitrotyrosine, superoxide anion (O2•-), receptor for the advanced glycation end products (RAGE) protein, and monocyte chemoattractant protein-1 (MCP-1) levels when compared to WT mice. High-sucrose intake caused a significant increase in body weight, postprandial glycemia, HbA1c, triglycerides, plasma vascular cell adhesion molecule 1 (VCAM-1), and vascular nitrotyrosine, O2•-, RAGE, and MCP-1 levels in both WT and 3xTg-AD mice when compared to the respective control group. Also, a significant decrease in nitric oxide-dependent vasorelaxation was observed in 3xTg-AD and sucrose-treated WT mice. In conclusion, AD and T2D promote similar vascular dysfunction of the aorta, this effect being associated with elevated oxidative and nitrosative stress and inflammation. Also, AD-associated vascular alterations are potentiated by T2D. These findings support the idea that metabolic alterations predispose to the onset and progression of dementia.

Abstract T P145: Incidence and Determinants of Clinical Dementia after Ischemic Stroke: a Population-based Study in Rochester, MN

Introduction: Studies have suggested a high incidence of dementia after stroke; however data regarding risk factors are conflicting and few studies are population-based. The aims of this population-based study are to determine the frequency of diagnosis and predictors of clinical dementia after ischemic stroke. Methods: The Rochester Epidemiology Project medical records linkage system was used to ascertain all first ischemic strokes (IS) occurring among Rochester, MN residents between 1990 -1994. Comprehensive medical records were reviewed. Patient and stroke characteristics, medical comorbidities, and the development of clinical dementia any time after IS were recorded. Dementia was defined as any reflection in the chart by a clinician of memory loss resulting in functional impairment. Patients with a pre-stroke diagnosis of dementia were excluded. Associations between new dementia after the index IS and other variables of interest were analyzed using univariate logistic regression. Results: First IS was detected in 490 people, 82 of whom had a prior history of dementia, and 119 (29%) of whom developed dementia during a mean follow-up of 6.5 years (range 0-23.8). The mean age at index stroke was 76.6 years (SD 12.9). Those who developed dementia were a mean 4 years older at the time of IS (p = 0.003). The odds of developing dementia were 1.7 higher in those who had at least one recurrent stroke. There was no effect of sex, stroke location (cortical, subcortical, brainstem), stroke mechanism, or premorbid stroke risk factors (coronary artery disease, atrial fibrillation/flutter, hypertension, diabetes mellitus, left-sided valvular disease) on the occurrence of dementia. Conclusions: Dementia is commonly diagnosed following ischemic stroke. While stroke risk factors did not impact the risk of diagnosis of dementia, recurrent stroke increased this risk. Stroke risk factors may indirectly increase the risk of dementia by increasing the risk of recurrent IS. This suggests that aggressive secondary stroke prevention measures may significantly decrease the risk of being diagnosed with dementia following IS.