Alzheimer's disease.

Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease.

Dementia in western Europe: epidemiological evidence and implications for policy making.

Dementia is receiving increasing attention from governments and politicians. Epidemiological research based on western European populations done 20 years ago provided key initial evidence for dementia policy making, but these estimates are now out of date because of changes in life expectancy, living conditions, and health profiles. To assess whether dementia occurrence has changed during the past 20-30 years, investigators of five different studies done in western Europe (Sweden [Stockholm and Gothenburg], the Netherlands [Rotterdam], the UK [England], and Spain [Zaragoza]) have compared dementia occurrence using consistent research methods between two timepoints in well-defined geographical areas.

Late effects of adjuvant chemotherapy for breast cancer on fine motor function.

Background: Adjuvant chemotherapy for breast cancer has been associated with deterioration of fine motor skill. Which aspects of motor performance are underlying this problem is unclear but important because manual motor deterioration could affect quality of life. The current study aims to investigate late effects of adjuvant chemotherapy for breast cancer on fine motor function, using both speed and accuracy measures.

Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.

Background: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting.

Methods: We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years.

Prevalence of cerebral small-vessel disease in long-term breast cancer survivors exposed to both adjuvant radiotherapy and chemotherapy.

Purpose: Adjuvant radiotherapy and chemotherapy for breast cancer have been related to transient ischemic attacks and stroke. To date, no studies have investigated the relationship between these adjuvant therapies and subclinical cerebral small-vessel disease in survivors of breast cancer. We compared white matter lesion (WML) volume and prevalence of brain infarctions and cerebral microbleeds (CMBs) between breast cancer survivors exposed to adjuvant radiotherapy and chemotherapy (aRCeBCSs) for primary disease and a population-based reference group.

Elevated HbA1c is associated with increased risk of incident dementia in primary care patients.

Type 2 diabetes mellitus (T2DM) is a risk factor of dementia. The effect of T2DM treatment quality on dementia risk, however, is unclear. 1,342 elderly individuals recruited via general practitioner registries (AgeCoDe cohort) were analyzed.

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described.

SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease.

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.

Brain cortical thickness in the general elderly population: the Rotterdam Scan Study.

Cortical thickness is considered a potentially relevant marker for neurodegenerative diseases. However, the relationship of demographic and vascular risk factors with cortical thickness remains unclear. In a population-based sample of 1022 non-demented elderly persons (mean age 68.

Late effects of adjuvant chemotherapy for adult onset non-CNS cancer; cognitive impairment, brain structure and risk of dementia.

Few studies have investigated the late (i.e. ≥ 5 years post-treatment) effects of chemotherapy for non-central nervous system (non-CNS) cancer on the brain.

The relation of uric acid to brain atrophy and cognition: the Rotterdam Scan Study.

Background: Uric acid has been associated with focal vascular brain disease. However, it is unknown whether uric acid also relates to global brain changes such as brain atrophy. We therefore studied the relation of uric acid to brain atrophy and whether this is accompanied by worse cognitive function.

Total antioxidant capacity of the diet and major neurologic outcomes in older adults.

Objective: To evaluate total antioxidant capacity of the diet, measured by the ferric-reducing antioxidant power (FRAP) assay, in relation to risks of dementia and stroke, as well as key structural brain volumes, in the elderly.

Methods: We prospectively studied 5,395 participants in the Rotterdam Study, aged 55 years and older, who were dementia free and provided dietary information at study baseline; 5,285 individuals were also stroke free at baseline, and 462 were dementia and stroke free at the time of an MRI brain scan 5 years after baseline. Dietary data were ascertained using a semiquantitative food-frequency questionnaire, and combined with food-specific FRAP measurements from published tables; this information was aggregated across the diet to obtain "dietary FRAP scores.

Global and focal white matter integrity in breast cancer survivors 20 years after adjuvant chemotherapy.

Objectives: To date, only four small studies have investigated the effects of adjuvant chemotherapy for breast cancer on the microstructure of cerebral white matter with magnetic resonance imaging (MRI). These studies, which were conducted shortly up to 10 years post-treatment, showed that chemotherapy is associated with focal loss of microstructural white matter integrity. We investigated the long-term effect of chemotherapy on white matter microstructural integrity by comparing the brains of chemotherapy-exposed breast cancer survivors to those of a population-based sample of women without a history of cancer.

The thyroid hormone receptor alpha locus and white matter lesions: a role for the clock gene REV-ERBα.

Background: Thyroid disorders are associated with an increased risk of cognitive impairment and Alzheimer's disease. Both small vessel disease and neurodegeneration have a role in the pathogenesis of cognitive impairment and Alzheimer's disease. Thyroid hormone receptor alpha (TRα) is the predominant TR in brain.

Discovery by the Epistasis Project of an epistatic interaction between the GSTM3 gene and the HHEX/IDE/KIF11 locus in the risk of Alzheimer's disease.

Despite recent discoveries in the genetics of sporadic Alzheimer's disease, there remains substantial "hidden heritability." It is thought that some of this missing heritability may be because of gene-gene, i.e.

Insulin resistance and the risk of stroke and stroke subtypes in the nondiabetic elderly.

Insulin resistance, which plays a key role in the development of diabetes mellitus, is a putative modifiable risk factor for stroke. The aim of this study was to investigate if markers of insulin resistance were associated with risk of stroke in the general elderly population. This study was part of the large population-based Rotterdam Study and included 5,234 participants who were aged 55 years or older and stroke free and diabetes free at baseline (1997-2001).

Assessment of cerebral small vessel disease predicts individual stroke risk.

Background: Despite several known risk factors it is still difficult to foresee who will develop a stroke and who will not. Vascular brain damage, visualised with MRI, reflects how the brain tolerates the effects of vascular risk factors and may therefore be relevant in predicting individual stroke risk.

Objective: To examine whether the presence of small vessel disease on brain MRI could improve the prediction of stroke beyond the classic stroke risk factors from the 1991 Framingham Stroke Risk Function.

Arterial stiffness and cerebral small vessel disease: the Rotterdam Scan Study.

Background And Purpose: Aging and vascular risk factors contribute to arterial stiffening. Increased arterial stiffness exposes the small vessels in the brain to abnormal flow pulsations and, as such, may contribute to the pathogenesis of cerebral small vessel disease. In a population-based study, we investigated the association between arterial stiffness, as measured by aortic pulse wave velocity (aPWV), and small vessel disease.

Retinopathy and risk of dementia: the Rotterdam Study.

Objective: To investigate the relation between retinopathy and the risk of dementia.

Methods: We investigated the associations between retinopathy and dementia and its subtypes Alzheimer disease (AD) and vascular dementia both cross-sectionally and prospectively in the Rotterdam Study, a large population-based cohort study. Digitized retinal images were available for 195 participants with prevalent dementia and 6,078 participants without dementia at baseline (1990-1993).

Alzheimer's disease genes and cognition in the nondemented general population.

Background: Genome-wide association studies have established 11 genes for late-onset Alzheimer's disease (AD). We investigated whether these genes jointly affect cognition in a nondemented population and improve prediction of AD.

Methods: In 5171 nondemented people (age 45-99 years) from the population-based Rotterdam Study, we genotyped APOE-ε4 and single nucleotide polymorphisms from the genes CLU, PICALM, BIN1, CR1, ABCA7, MS4A6A, MS4A4E, CD2AP, EPHA1, and CD33.

Dietary intakes of berries and flavonoids in relation to cognitive decline.

Objective: Berries are high in flavonoids, especially anthocyanidins, and improve cognition in experimental studies. We prospectively evaluated whether greater long-term intakes of berries and flavonoids are associated with slower rates of cognitive decline in older women.

Methods: Beginning in 1980, a semiquantitative food frequency questionnaire was administered every 4 years to Nurses' Health Study participants.

Common variants at 12q14 and 12q24 are associated with hippocampal volume.

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7).

Common variants at 6q22 and 17q21 are associated with intracranial volume.

During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 × 10(-8)) for brain volume.

Trends in stroke incidence rates and stroke risk factors in Rotterdam, the Netherlands from 1990 to 2008.

Stroke incidence rates have decreased in developed countries over the past 40 years, but trends vary across populations. We investigated whether age-and-sex-specific stroke incidence rates and associated risk factors as well as preventive medication use have changed in Rotterdam in the Netherlands during the last two decades. The study was part of the Rotterdam Study, a large population-based cohort study among elderly people.