Chengxuan Qiu

The age-dependent relation of blood pressure to cognitive function and dementia

The relation of blood pressure with cognitive function and dementia has, in recent years, received much attention from epidemiological research. Some cross-sectional studies have shown an inverse association between blood pressure and the prevalence of dementia and Alzheimers disease, whereas longitudinal studies yield mixed results that largely depend on the age at which blood pressure is measured and the time interval between blood pressure and outcome assessments. Some studies suggest that midlife high blood pressure is a risk factor for late-life cognitive impairment and dementia, and that low diastolic pressure and very high systolic pressure in older adults may be associated with subsequent development of dementia and Alzheimers disease. Observational studies and randomised clinical trials provide limited evidence for a protective effect of antihypertensive therapy against dementia and stroke-related cognitive decline. Atherosclerosis resulting from long-standing hypertension, and cerebral hypoperfusion secondary to severe atherosclerosis and to low blood pressure may be major biological pathways linking both high blood pressure in midlife and low blood pressure in late-life to cognitive decline and dementia.

Diabetes mellitus and risk of dementia in the Kungsholmen project A 6-year follow-up study

Background: Research on diabetes mellitus as a risk factor for dementia and its main subtypes has produced conflicting results. The authors investigated the relationship between diabetes mellitus and risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD). Methods: A dementia-free cohort of 1,301 community dwellers aged 75 years and older in Stockholm, Sweden, was longitudinally examined twice over 6 years to detect dementia cases (Diagnostic and Statistical Manual of Mental Disorders–III-R diagnostic criteria). Cox proportional hazards models were used to analyze the data with adjustment for several potential confounders. Results: During the 5,584 person-years of follow-up, 350 subjects developed dementia, including 260 AD and 49 VaD cases. Diabetes mellitus was associated with hazard ratios (HR) of 1.5 (95% CI 1.0 to 2.1, p = 0.04) for dementia, 2.6 (95% CI 1.2 to 6.1) for VaD, and 1.3 (95% CI 0.9 to 2.1) for AD. Patients who were treated with oral antidiabetic medications had HRs of 1.7 (95% CI 1.0 to 2.8, p = 0.04) for dementia and 3.6 (95% CI 1.3 to 9.5) for VaD. There were significant interactions of diabetes with severe systolic hypertension (≥180 mm Hg) on dementia and its main subtypes, and of diabetes with heart disease on VaD. Conclusions: Diabetes mellitus increases the risk of dementia, and VaD in particular, in very old people. The risk for dementia and VaD is especially high when diabetes mellitus occurs together with severe systolic hypertension or heart disease.

The epidemiology of the dementias: an update.

Purpose of review The epidemiology of dementia is one of the priority fields in aging research. This review aims to highlight the most relevant findings over last years concerning occurrence, risk factors, and prevention of dementia and its major subtypes. Recent findings It is estimated that currently around 24 million people have dementia in the world, with the number being projected to double every 20 years, and that 60% of dementia patients live in developing countries, with the proportion being raised to more than 70% by 2040. Current evidence suggests that vascular factors, such as midlife hypertension, diabetes, and cerebrovascular disease, contribute significantly to the development of dementia and Alzheimers disease, and that active engagement in mental, physical, and social activities may postpone the onset of dementia by providing cognitive reserve. Summary Dementia represents a major public health challenge as a consequence of rapid increase in the aging population worldwide, especially in developing countries. This challenge can be partly confronted by successful development of preventive strategies. Evidence has emerged that proper control of vascular disorders and maintenance of active lifestyles may prevent or delay the onset and progression of dementia and Alzheimers disease. Intervention trials are warranted to determine, to what extent, such programs are effective against dementia.

Defeating Alzheimer's disease and other dementias: a priority for European science and society

Defeating Alzheimers disease and other dementias : a priority for European science and society

Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden

Objective: To explore whether prevalence, survival, and incidence of dementia have changed from 1987–1994 to 2001–2008 in Stockholm, Sweden. Methods: This study is based on 2 cross-sectional surveys of people aged 75 years or over conducted in central Stockholm: the Kungsholmen Project (KP) (1987–1989, n = 1,700) and the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) (2001–2004, n = 1,575). In both surveys we diagnosed dementia according to DSM-III-R criteria, following the identical diagnostic procedure. Death certificates were used to determine survival status of KP participants as of December 1994 and SNAC-K participants as of June 2008. We used logistic and Cox models to compare prevalence and survival, controlling for major confounders. We inferred incidence of dementia according to its relationship with prevalence and survival. Results: At baseline, 225 subjects in KP and 298 in SNAC-K were diagnosed with dementia. The age- and sex-standardized prevalence of dementia was 17.5% (12.8% in men; 19.2% in women) in KP and 17.9% (10.8% in men; 20.5% in women) in SNAC-K. The adjusted odds ratio of dementia in SNAC-K vs KP was 1.17 (95% confidence interval 0.95–1.46). The multiadjusted hazard ratio of death in SNAC-K vs KP was 0.71 (0.57–0.88) in subjects with dementia, 0.68 (0.59–0.79) in those without dementia, and 0.66 (0.59–0.74) in all participants. Conclusions: Prevalence of dementia was stable from the late 1980s to the early 2000s in central Stockholm, Sweden, whereas survival of patients with dementia increased. These results suggest that incidence of dementia may have decreased during this period.

Mid- and late-life diabetes in relation to the risk of dementia: a population-based twin study.

OBJECTIVE—We aimed to verify the association between diabetes and the risk of dementia, Alzheimers disease, and vascular dementia in twins and to explore whether genetic and early-life environmental factors could contribute to this association. RESEARCH DESIGN AND METHODS—This study included 13,693 twin individuals aged ≥65 years. Dementia was diagnosed according to DSM-IV (Diagnostic Manual of Mental Disorders, 4th ed.) criteria. Information on diabetes was collected from the inpatient registry and self- or informant-reported history of diabetes. Data were analyzed following two strategies: 1) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models and 2) cotwin matched case-control analysis for dementia-discordant twin pairs using conditional logistic regression. RESULTS—Of all participants, 467 were diagnosed with dementia, including 292 with Alzheimers disease and 105 with vascular dementia, and an additional 170 were diagnosed with questionable dementia. Diabetes was present in 1,396 subjects. In GEE models, diabetes was associated with adjusted odds ratios (ORs) (95% CI) of 1.89 (1.51–2.38) for dementia, 1.69 (1.16–2.36) for Alzheimers disease, and 2.17 (1.36–3.47) for vascular dementia. Compared with late-life diabetes (onset age ≥65 years), the risk effect of mid-life diabetes (onset age <65 years) on dementia was stronger. Conditional logistic analysis of 210 dementia-discordant twin pairs led to ORs of 2.41 (1.05–5.51) and 0.68 (0.30–1.53) for dementia related to mid- and late-life diabetes, respectively. CONCLUSIONS—Diabetes increases the risk of Alzheimer disease and vascular dementia. The risk is stronger when diabetes occurs at mid-life than in late life. Genetic and early-life environmental factors might contribute to the late-life diabetes–dementia association but could not account for the mid-life diabetes–dementia association.

The Effect of Borderline Diabetes on the Risk of Dementia and Alzheimer’s Disease

To verify the hypothesis that borderline diabetes may increase the risk of dementia and Alzheimer’s disease, a community-based cohort of 1,173 dementia- and diabetes-free individuals aged ≥75 years was longitudinally examined three times to detect patients with dementia and Alzheimer’s disease (Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria). Borderline diabetes was defined as a random plasma glucose level of 7.8–11.0 mmol/l. Data were analyzed using Cox proportional hazards models. During the 9-year follow-up, 397 subjects developed dementia, including 307 Alzheimer’s cases. At baseline, 47 subjects were identified with borderline diabetes. Borderline diabetes was associated with adjusted hazard ratios (95% CIs) of 1.67 (1.04–2.67) for dementia and 1.77 (1.06–2.97) for Alzheimer’s disease; the significant associations were present after additional adjustment for future development of diabetes. Stratified analysis suggested a significant association between borderline diabetes and Alzheimer’s disease only among noncarriers of APOE ε4 allele. There was an interaction between borderline diabetes and severe systolic hypertension on the risk of Alzheimer’s disease (P = 0.04). We conclude that borderline diabetes is associated with increased risks of dementia and Alzheimer’s disease; the risk effect is independent of the future development of diabetes. Borderline diabetes may interact with severe systolic hypertension to multiply the risk of Alzheimer’s disease.

Pulse Pressure and Risk of Alzheimer Disease in Persons Aged 75 Years and Older A Community-Based, Longitudinal Study

Background and Purpose— Elevated blood pressure has been found to increase the risk of dementia, including Alzheimer disease. We sought to investigate whether pulse pressure was predictive of Alzheimer disease and dementia. Methods— A community-based, dementia-free cohort (n=1270) aged ≥75 years was clinically examined twice over 6 years to detect incident dementia with the use of the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Cox proportional hazards models were used to analyze pulse pressure in association with incident Alzheimer disease and dementia after adjustment for several potential confounders, including systolic pressure and diastolic pressure. Results— During the 5464.6 person-years (median, 4.7 years) of follow-up, 339 subjects developed dementia, including 256 Alzheimer disease cases. Pulse pressure as a continuous variable was not statistically related to the risk of Alzheimer disease and dementia. In the categorical analysis, however, in comparison with median tertile of pulse pressure (70 to 84 mm Hg), subjects with higher pulse pressure had adjusted relative risks (95% CI) of 1.4 (1.0 to 2.0;P =0.04) for Alzheimer disease and 1.3 (0.9 to 1.7) for dementia. The corresponding figures related to lower pulse pressure were 1.7 (1.2 to 2.3) for Alzheimer disease and 1.4 (1.0 to 1.9;P =0.03) for dementia. This association was particularly pronounced among women. Conclusions— Higher pulse pressure is associated with increased risk for Alzheimer disease and dementia in old adults, which is probably due to artery stiffness and severe atherosclerosis. Poor cerebral perfusion related to decreased pulse pressure may explain the association between lower pulse pressure and increased dementia risk.

Accelerated Progression from Mild Cognitive Impairment to Dementia in People with Diabetes

OBJECTIVE The effect of diabetes on mild cognitive impairment (MCI) and its conversion to dementia remains controversial. We sought to examine whether diabetes and pre-diabetes are associated with MCI and accelerate the progression from MCI to dementia. RESEARCH DESIGN AND METHODS In the Kungsholmen Project, 963 cognitively intact participants and 302 subjects with MCI (120 with amnestic MCI [aMCI ] and 182 with other cognitive impairment no dementia [oCIND]) age ≥75 years were identified at baseline. The two cohorts were followed for 9 years to detect the incident MCI and dementia following international criteria. Diabetes was ascertained based on a medical examination, hypoglycemic medication use, and random blood glucose level ≥11.0 mmol/l. Pre-diabetes was defined as random blood glucose level of 7.8–11.0 mmol/l in diabetes-free participants. Data were analyzed using standard and time-dependent Cox proportional-hazards models. RESULTS During the follow-up period, in the cognitively intact cohort, 182 people developed MCI (42 aMCI and 140 oCIND), and 212 developed dementia. In the MCI cohort, 155 subjects progressed to dementia, the multi-adjusted hazard ratio (95% CI) of dementia was 2.87 (1.30–6.34) for diabetes, and 4.96 (2.27–10.84) for pre-diabetes. In a Kaplan-Meier survival analysis, diabetes and pre-diabetes accelerated the progression from MCI to dementia by 3.18 years. Diabetes and pre-diabetes were neither cross-sectionally nor longitudinally associated with MCI. CONCLUSIONS Diabetes and pre-diabetes substantially accelerate the progression from MCI to dementia, and anticipate dementia occurrence by more than 3 years in people with MCI. The association of diabetes with the development of MCI is less evident in old people.

Decline in blood pressure over time and risk of dementia : a longitudinal study from the Kungsholmen project

Background and Purpose— Low blood pressure has been related to an increased risk of dementia. We sought to verify blood pressure variations before and after a dementia diagnosis and to relate blood pressure decline to subsequent Alzheimer disease and dementia. Methods— A community dementia-free cohort aged ≥75 years (n=947) underwent follow-up examinations twice over a period of 6 years to detect dementia cases (Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised [DSM-III-R] criteria, n=304). Blood pressure variation before and after dementia diagnosis was verified with linear mixed-effects models. Using the dementia-free cohort identified at first follow-up (n=719), the association between blood pressure decline from baseline to first follow-up and subsequent risk of dementia was examined. Results— Blood pressure markedly decreased over 3 years before dementia diagnosis and afterward, whereas no substantial decline was present 3 to 6 years before the diagnosis. However, among subjects with baseline systolic pressure <160 mm Hg, systolic pressure decline ≥15 mm Hg occurring 3 to 6 years before diagnosis was associated with relative risks (95% CI) of 3.1 (1.3 to 7.0) for Alzheimer disease and 3.1 (1.5 to 6.3) for dementia. There was a dose–response relationship between systolic pressure decline and dementia risk in subjects with vascular disease. Conclusions— Blood pressure starts to decrease only 3 years before dementia diagnosis and continues to decline afterward. A greater decline in systolic pressure occurring 3 to 6 years before diagnosis is associated with an increased risk of dementia only in older people with already low blood pressure or affected by vascular disorders.