Induction of serpinb1a by PACAP or NGF is required for PC12 cells survival after serum withdrawal.

PC12 cells are used to study the signaling mechanisms underlying the neurotrophic and neuroprotective activities of pituitary adenylate cyclase-activating polypeptide (PACAP) and nerve growth factor (NGF). Previous microarray experiments indicated that serpinb1a was the most induced gene after 6 h of treatment with PACAP or NGF. This study confirmed that serpinb1a is strongly activated by PACAP and NGF in a time-dependent manner with a maximum induction (~ 50-fold over control) observed after 6 h of treatment.

Positive association between plasma amylin and cognition in a homebound elderly population.

Our recent study reported that amylin, a pancreatic peptide that readily crosses the blood-brain barrier, improves learning and memory in Alzheimer's disease mouse models. However, the relationship between peripheral amylin and cognition in humans is unknown. In this follow-up study, using a cross-sectional, homebound elderly population, improvement in cognitive function with increasing quartiles of plasma amylin was suggested by positive association with verbal memory (p = 0.

Prospective memory predicts the level of community living skills in schizophrenia.

Schizophrenia patients are known to have prospective memory (PM) deficits. There is no robust evidence showing that PM deficits have a major impact on community living skills in schizophrenia. The aim of this study was to examine the association between PM and community living skills in schizophrenia.

Susceptibility of the conventional criteria for mild cognitive impairment to false-positive diagnostic errors.

Background: We assessed whether mild cognitive impairment (MCI) subtypes could be empirically derived within the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI cohort and examined associated biomarkers and clinical outcomes.

Methods: Cluster analysis was performed on neuropsychological data from 825 MCI ADNI participants.

Results: Four subtypes emerged: (1) dysnomic (n = 153), (2) dysexecutive (n = 102), (3) amnestic (n = 288), and (4) cluster-derived normal (n = 282) who performed within normal limits on cognitive testing.

Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates.

We compared two methods of diagnosing mild cognitive impairment (MCI): conventional Petersen/Winblad criteria as operationalized by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and an actuarial neuropsychological method put forward by Jak and Bondi designed to balance sensitivity and reliability. 1,150 ADNI participants were diagnosed at baseline as cognitively normal (CN) or MCI via ADNI criteria (MCI: n = 846; CN: n = 304) or Jak/Bondi criteria (MCI: n = 401; CN: n = 749), and the two MCI samples were submitted to cluster and discriminant function analyses. Resulting cluster groups were then compared and further examined for APOE allelic frequencies, cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker levels, and clinical outcomes.

Insulin-like growth factor-1 and risk of Alzheimer dementia and brain atrophy.

Objective: To relate serum insulin-like growth factor-1 (IGF-1) to risk of Alzheimer disease (AD) dementia and to brain volumes in a dementia-free community sample spanning middle and older ages.

Methods: Dementia-free Framingham participants from generation 1 (n = 789, age 79 ± 4 years, 64% women) and generation 2 (n = 2,793, age 61 ± 9 years, 55% women; total = 3,582, age 65 ± 11 years, 57% women) had serum IGF-1 measured in 1990-1994 and 1998-2001, respectively, and were followed prospectively for incident dementia and AD dementia. Brain MRI was obtained in stroke- and dementia-free survivors of both generations 1 (n = 186) and 2 (n = 1,867) during 1999-2005.

Association between neuropathology and brain volume in the Framingham Heart Study.

Studies of clinical and community cohorts have shown that antemortem imaging measures of hippocampal volume have correlated with postmortem Alzheimer pathology. Fewer studies have examined the relationship between both Alzheimer and cerebrovascular pathology, and antemortem brain imaging. The aim of this study was to correlate antemortem brain magnetic resonance imaging (MRI) volumes with postmortem brain pathology (both Alzheimer-related and cerebrovascular) in a community-derived cohort from the Framingham Heart Study.

Executive function and mortality in homebound elderly adults.

Objectives: To determine the association between executive function and mortality in homebound elderly adults.

Design: Longitudinal study.

Setting: Four home care agencies in the Boston area.

Gender and incidence of dementia in the Framingham Heart Study from mid-adult life.

Background: Gender-specific risks for dementia and Alzheimer's disease (AD) starting in midlife remain largely unknown.

Methods: Prospectively ascertained dementia/AD and cause-specific mortality in Framingham Heart Study (FHS) participants was used to generate 10- to 50-year risk estimates of dementia/AD on the basis of the Kaplan-Meier method (cumulative incidence) or accounting for competing risk of death (lifetime risk [LTR]).

Results: Overall, 777 cases of incident dementia (601 AD) occurred in 7901 participants (4333 women) over 136,266 person-years.

Predictive value of prospective memory for remission in first-episode schizophrenia.

Purpose: The study examined the rate of remission in individuals experiencing a first episode of schizophrenia (FES) in China and explored predictors of remission in the acute phase of the illness.

Design And Methods: Fifty-five FES patients were randomly treated with risperidone, olanzapine, or aripiprazole at therapeutic doses for 8 weeks, and their clinical profiles and cognition were assessed using standardized assessment instruments at entry and the end of the study.

Findings: Of the 55 patients, 30 (54.

Quality of life of patients with euthymic bipolar disorder and its associations with demographic and clinical characteristics, psychopathology, and cognitive deficits.

Purpose: Little is known about quality of life (QOL) in Chinese patients with bipolar disorder (BD) in remission (euthymia). This study examined the QOL of such a cohort of BD patients and its demographic, clinical, and cognitive correlates.

Design And Methods: Forty-seven euthymic BD patients and 47 matched healthy controls formed the study sample.

Development of a silver in situ hybridisation based assay for the determination of ploidy status in molar pregnancy diagnosis.

The aim of this study was to establish a scoring method for ploidy analysis using silver in situ hybridisation (SISH) with a chromosome 17 centromere probe. SISH was performed using the Ventana chromosome 17 centromere probe on sections from formalin fixed, paraffin embedded archival cases of complete hydatidiform moles, partial hydatidiform moles and hydropic products of conception with previously established ploidy status (determined by flow cytometry or karyotyping). In order to determine ploidy status, a scoring method was developed based on both the average number of signals per nucleus (ASN) and the percentage of nuclei with three signals (N3S), enumerated in 50 villous cytotrophoblastic and/or stromal cells.

Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham Heart Study.

Importance: In animal studies, brain-derived neurotrophic factor (BDNF) has been shown to impact neuronal survival and function and improve synaptic plasticity and long-term memory. Circulating BDNF levels increase with physical activity and caloric restriction, thus BDNF may mediate some of the observed associations between lifestyle and the risk for dementia. Some prior studies showed lower circulating BDNF in persons with Alzheimer disease (AD) compared with control participants; however, it remains uncertain whether reduced levels precede dementia onset.

Parental longevity is associated with cognition and brain ageing in middle-aged offspring.

Background: offspring of long-lived individuals have lower risk for dementia. We examined the relation between parental longevity and cognition and subclinical markers of brain ageing in community-dwelling adult offspring.

Methods: offspring participants with both parents in the Framingham Heart Study, aged ≥55 years and dementia-free underwent baseline and repeat neuropsychological (NP) testing and brain magnetic resonance imaging (MRI).

COSMIC (Cohort Studies of Memory in an International Consortium): an international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups.

Background: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.

Qualitative neuropsychological measures: normative data on executive functioning tests from the Framingham offspring study.

Unlabelled: BACKGROUND/STUDY CONTEXT: Studies have found that executive functioning is affected early in the pathophysiological processes associated with Alzheimer's disease and vascular dementia. There also exists a range of functioning on executive tasks during normal aging. Although qualitative data are commonly utilized in clinical practice for evaluating subtle changes in cognitive functioning and diagnostic discernment, it is not clear whether error responses used in clinical practice are also evident as normative behavior.

Prospective memory impairment and its implications for community living skills in bipolar disorder.

Objective: Prospective memory (PM) refers to the ability to undertake intended actions in the future. The functional significance of PM in bipolar disorder (BD) has not yet been investigated. This study examined PM impairment and its role in community living skills in clinically stable individuals with BD.

Midlife cardiovascular risk impacts executive function: Framingham offspring study.

Introduction: Novel error scores and traditional indices of executive function (EF) were related to cardiovascular risk factors measured 10 to 15 years earlier.

Methods: From 1991 to 1995, the Framingham Stroke Risk Profile (FSRP), a composite score of cardiovascular risk, was ascertained in 1755 Framingham Offspring participants (54% women, mean age=54±9 y). Participants were administered EF tests, which included: FAS and Animals Fluency tests, Trail Making Test B (TrB), and Digit Span-Backwards (DS-B), from 2005 to 2009.

Object motion continuity and the flash-lag effect.

When a visual object is briefly flashed, it appears to lag behind another moving object (flash-lag effect; FLE). Previous studies showed that a sudden change to the moving object at the time of the flash presentation would eliminate the FLE. We examined whether the FLE would be eliminated when a sudden color change was embedded in a sequence of color alternations on a moving object.

Lexical retrieval in discourse: an early indicator of Alzheimer's dementia.

We examined the progression of lexical-retrieval deficits in individuals with neuropathologically determined Alzheimer's disease (AD; n = 23) and a comparison group without criteria for AD (n = 24) to determine whether linguistic changes were a significant marker of the disease. Our participants underwent multiple administrations of a neuropsychological battery, with initial administration occurring on average 16 years prior to death. The battery included the Boston Naming Test (BNT), a letter fluency task (FAS) and written description of the Cookie Theft Picture (CTP).

Relations of arterial stiffness and endothelial function to brain aging in the community.

Objective: To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging.

Methods: Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively).

Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury: Framingham Study.

Background And Purpose: Brain-derived neurotrophic factor (BDNF), a major neurotrophin and vascular endothelial growth factor (VEGF) have a documented role in neurogenesis, angiogenesis, and neuronal survival. In animal experiments, they impact infarct size and functional motor recovery after an ischemic brain lesion. We sought to examine the association of serum BDNF and VEGF with the risk of clinical stroke or subclinical vascular brain injury in a community-based sample.

Brain imaging and cognitive predictors of stroke and Alzheimer disease in the Framingham Heart Study.

Background And Purpose: Exposure to vascular risk factors has a gradual deleterious effect on brain MRI and cognitive measures. We explored whether a pattern of these measures exists that predicts stroke and Alzheimer disease (AD) risk.

Methods: A cognitive battery was administered to 1679 dementia and stroke-free Framingham offspring (age, >55 years; mean, 65.

APOE genotype and MRI markers of cerebrovascular disease: systematic review and meta-analysis.

Objective: We aimed to examine the association of APOE ε genotype with MRI markers of cerebrovascular disease (CVD): white matter hyperintensities, brain infarcts, and cerebral microbleeds.

Methods: We performed a systematic review and meta-analysis of 42 cross-sectional or longitudinal studies identified in PubMed from 1966 to June 2012 (n = 29,965). This included unpublished data from 3 population-based studies: 3C-Dijon, Framingham Heart Study, and Sydney Memory and Ageing Study.

Assessment of prospective memory in schizophrenia using the Chinese version of the Cambridge Prospective Memory Test: a controlled study.

Introduction: Data on the psychometric assessment of prospective memory (PM) are limited. The Cambridge Prospective Memory Test (CAMPROMPT) and its Chinese version (CAMPROMPT-C) have been applied to a variety of clinical conditions except for chronic schizophrenia. This controlled study explored the clinical utility of the CAMPROMPT-C in patients with schizophrenia by comparing their PM performance with that of normal controls.