Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort.

Objectives: To determine whether coronary artery disease, peripheral arterial disease (PAD), or noninvasive markers of cardiovascular disease (CVD) predict the onset of dementia and Alzheimer's disease (AD).

Design: Longitudinal cohort study.

Setting: Four U.

Heritability of psychosis in Alzheimer disease.

Objective: The authors have previously demonstrated familial clustering of psychotic symptoms in late-onset Alzheimer disease (LOAD+P) and sought to estimate and explore the nature of the heritability of LOAD+P.

Methods: The heritability of LOAD+P, defined by single and multiple psychotic symptoms, was estimated with data from the National Institute of Mental Health AD Genetics Initiative.

Results: The estimated heritability for LOAD+P defined by multiple psychotic symptoms was 61%; for LOAD+P defined by any occurrence of psychotic symptoms, it was 30%.

Immunohistochemical study of the hnRNP A2 and B1 in the hippocampal formations of brains with Alzheimer's disease.

To elucidate the post-transcriptional regulation in the subjects with Alzheimer's disease (AD), we employed immunohistochemical techniques and examined the expression of the heterogeneous nuclear ribonucleoprotein (hnRNP) A2 and B1 in the hippocampus with neurofibrillary tangle (NFT) neuropathology. In the mildly affected subjects (Braak stages I and II), the most intense A2 immunoreactivity was observed in the CA3 to CA1 neurons. In the moderately (Braak stages III and IV) and severely affected subjects (Braak stages V and VI), the CA1 region demonstrated a decrease in the number of A2 immunoreactive neurons and in immunoreactivity in the remaining neurons, while within the CA4 to CA2 in the severely affected subjects, the majority of neurons showed increased A2 immunoreactivity.

Chronic traumatic encephalopathy in a National Football League player.

Objective: We present the results of the autopsy of a retired professional football player that revealed neuropathological changes consistent with long-term repetitive concussive brain injury. This case draws attention to the need for further studies in the cohort of retired National Football League players to elucidate the neuropathological sequelae of repeated mild traumatic brain injury in professional football.

Methods: The patient's premortem medical history included symptoms of cognitive impairment, a mood disorder, and parkinsonian symptoms.

Alzheimer disease subjects with psychosis have increased schizotypal symptoms before dementia onset.

Background: Recent findings have demonstrated the familiality of psychotic symptoms occurring during Alzheimer disease (AD with psychosis, AD+P), particularly for subjects with multiple psychotic symptoms. We have proposed a model in which genes that confer a small risk for psychosis interact with neurodegenerative illness to yield manifest psychotic symptoms during AD. One prediction of this model would be that AD+P subjects would have evidence of increased degrees of subsyndromal psychosis before AD onset.

Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment.

Background: Subjects with mild cognitive impairment (MCI) have been shown to have reduced hippocampal volumes relative to normal elderly control subjects. The presence of the apolipoprotein E epsilon4 (APOE*E4) allele has been associated with greater hippocampal atrophy in women than in men with Alzheimer disease. This relationship has not been demonstrated in MCI.

Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B.

A valid quantitative imaging method for the measurement of amyloid deposition in humans could improve Alzheimer's disease (AD) diagnosis and antiamyloid therapy assessment. Our group developed Pittsburgh Compound-B (PIB), an amyloid-binding radiotracer, for positron emission tomography (PET). The current study was aimed to further validate PIB PET through quantitative imaging (arterial input) and inclusion of subjects with mild cognitive impairment (MCI).

Caregiving burden and psychiatric morbidity in spouses of persons with mild cognitive impairment.

Background: While the deleterious psychosocial and mental health effects of dementia caregiving are firmly established, very little is known about the burdens or psychiatric outcomes of providing care to a spouse with less severe cognitive impairment, such as mild cognitive impairment (MCI). We characterized the nature and level of caregiver burden and psychiatric morbidity in spouses of persons diagnosed with MCI.

Methods: Interview assessments were completed on a cohort of 27 spouses of persons with a recent diagnosis of MCI.

Three SNPs in the GSTO1, GSTO2 and PRSS11 genes on chromosome 10 are not associated with age-at-onset of Alzheimer's disease.

Linkage studies suggest the presence of putative risk and/or age-at-onset genes for Alzheimer's disease on Chromosome 10. Recently, a genomic converging approach using a combination of linkage, expression and association studies has reported significant associations of the glutathione S-transferase omega 1 and 2 (GSTO1 and GSTO2) genes and possibly the protease serine 11 (PRSS11) gene on chromosome 10 with age-at-onset, but not risk, for Alzheimer's disease (AD) and Parkinson disease. We investigated the association of the reported three polymorphisms in 990 sporadic late-onset AD cases (26% autopsy confirmed) and 735 controls.

Apolipoprotein D is a component of compact but not diffuse amyloid-beta plaques in Alzheimer's disease temporal cortex.

Apolipoprotein D (apoD) is elevated in Alzheimer's disease (AD) cortex, localizing to cells, blood vessels, and neuropil deposits (plaques). The role of apoD in AD pathology and the extent of its co-distribution with diffuse (amorphous) and compact (dense fibrillar) amyloid-beta (Abeta) plaques are currently unclear. To address this issue, we combined apoD and Abeta immunohistochemistry with ThioS/X-34 staining of the beta-pleated sheet protein conformation in temporal cortex from 36 AD patients and 12 non-demented controls.

Alzheimer disease and mortality: a 15-year epidemiological study.

Background: Alzheimer disease (AD) is considered a leading cause of death, but few studies have examined the contribution of AD to mortality based on follow-up of representative US cohorts.

Objective: To examine mortality rates, duration of survival, causes of death, and the contribution of AD to the risk of mortality in an aging community-based cohort, controlling for other predictors.

Design: Fifteen-year prospective epidemiological study.

Cognitive correlates of alterations in acetylcholinesterase in Alzheimer's disease.

We recently reported findings of modest loss of cortical acetylcholinesterase (AChE) activity in patients with overall mild Alzheimer's disease (AD) using N-[11C]methyl-pi-peridin-4-yl propionate ([11C]PMP) AChE positron emission tomography (PET). To determine cognitive correlates of in vivo cortical AChE activity in patients with mild to moderate AD (n=15), and in normal controls (NC, n=12) using [11C]PMP AChE PET imaging. Mean cortical AChE activity in the AD subjects was mildly reduced (-11.

Investigation of the effect of brain-derived neurotrophic factor (BDNF) polymorphisms on the risk of late-onset Alzheimer's disease (AD) and quantitative measures of AD progression.

BDNF is a functional candidate gene for AD, owing to its role in neuronal development and survival. The Val66Met (G196A), along with another C270T polymorphism has been associated with AD, however, the effects seem to be inconsistent across studies. We examined the association of the G196A and C270T polymorphisms with sporadic late-onset AD (LOAD) in a large American White cohort of 995 AD cases and 671 controls and an American Black cohort of 64 AD cases and 45 controls.

Reduction of choline acetyltransferase activity in primary visual cortex in mild to moderate Alzheimer's disease.

Background: Cholinergic deficits in the primary visual cortex (PVC) may underlie some of the abnormalities in visual processing and global cognitive performance in Alzheimer's disease (AD).

Objective: To correlate measures of general cognition (Mini-Mental State Examination and Global Cognitive Score) and visuospatial function with choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities, and nerve growth factor protein levels in the PVC.

Design: The ChAT and AChE enzyme assays and a nerve growth factor protein enzyme-linked immunoabsorbent assay were performed on PVC tissue samples from subjects clinically diagnosed as having mild cognitive impairment (MCI), AD, or no cognitive impairment (NCI).

Changes in hippocampal GABABR1 subunit expression in Alzheimer's patients: association with Braak staging.

Alterations in the gamma-aminobutyric acid (GABA) neurotransmitter and receptor systems may contribute to vulnerability of hippocampal pyramidal neurons in Alzheimer's disease (AD). The present study examined the immunohistochemical localization and distribution of GABA(B) receptor R1 protein (GBR1) in the hippocampus of 16 aged subjects with a range of neurofibrillary tangle (NFT) pathology as defined by Braak staging (I-VI). GBR1 immunoreactivity (IR) was localized to the soma and processes of hippocampal pyramidal cells and some non-pyramidal interneurons.

Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from infants with inflicted brain injury from child abuse.

Previous studies suggest that delayed neuronal death occurs in patients with inflicted traumatic brain injury (TBI) from child abuse. It is unknown whether the mode of this delayed neuronal death represents apoptosis or necrosis, a distinction that carries therapeutic ramifications. Cytochrome c, an electron transport chain component, can be released from mitochondria under conditions of cellular stress, whereupon it can initiate and serve as a biomarker of apoptosis.

Imaging technology for neurodegenerative diseases: progress toward detection of specific pathologies.

Advances in neuroimaging over the past 2 decades are products of breakthroughs in imaging technology, developments of more powerful computers and image-processing software, and expanding knowledge in basic and clinical neuroscience. In addition to the insights into normal brain structure and function that such methods provide and the information that can be gained from disease-related changes in structure and function, the promise of achieving diagnostic specificity through neuroimaging lies with the potential identification of pathognomonic proteins. Recent advances in imaging beta-amyloid plaques, one of the hallmarks of Alzheimer disease, offer such a technological breakthrough and the possibility for more efficient assessment of antiamyloid interventions as well as specific noninvasive diagnostic capabilities.

Alteration of a clinically meaningful outcome in the natural history of Alzheimer's disease by cholinesterase inhibition.

Objectives: To describe the effect of cholinesterase inhibitors (CEIs) on the natural course of Alzheimer's disease (AD) using clinically meaningful outcomes.

Design: Cross-sectional and longitudinal study.

Setting: Referral dementia clinic.

Immunohistochemical study of hnRNP B1 in the postmortem temporal cortices of patients with Alzheimer's disease.

In order to examine the post-transcriptional regulations in Alzheimer's disease, we employed immunohistochemical techniques and examined the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 in the inferior temporal cortex of subjects with Alzheimer's disease. In the mild cases, intense B1 immunoreactivity was observed in neurons of layer V, and less intense immunoreactivity was observed in layers II and III. The overall distributions and intensities of B1 immunoreactivity were undistinguishable among mild, moderate, and severe cases.

Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury.

Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer's disease (AD). This immunohistochemical study determined the extent of AD-related changes in temporal cortex resected from individuals treated surgically for severe TBI. Antisera generated against Abeta species (total Abeta, Abeta(1-42), and Abeta(1-40)), the C-terminal of the Abeta precursor protein (APP), apolipoprotein E (apoE), and markers of neuron structure and degeneration (tau, ubiquitin, alpha-, beta-, and gamma-synuclein) were used to examine the extent of Abeta plaque deposition and neurodegenerative changes in 18 TBI subjects (ages 18-64 years).

Detection and management of cognitive impairment in primary care: The Steel Valley Seniors Survey.

Objectives: To identify characteristics of older primary care patients who were cognitively impaired and who underwent mental status testing by their physicians.

Design: Cross-sectional and retrospective analysis.

Setting: Seven small-town primary care practices.

Neuropathologic correlates of late-onset major depression.

Late life major depression (LLMD) is frequently associated with cognitive impairment, and increases the risk for subsequent dementia. Cerebrovascular disease, Alzheimer's disease (AD), and dementia with Lewy bodies (DLB) have all been hypothesized to contribute to this increased risk, though prospective studies have yet to examine these hypotheses with autopsy confirmation of the clinical diagnoses. The aim of this study is to examine the rates of cerebrovascular, AD, and DLB pathology among the first 10 participants in an LLMD brain tissue donation program.

Hemoglobin levels and Alzheimer disease: an epidemiologic study in India.

Objective: Anemia is common in developing countries, where populations are aging rapidly. The authors explored the cross-sectional relationship between hemoglobin concentration and Alzheimer disease (AD) in a rural elderly sample in Ballabgarh, India.

Methods: A clinical diagnostic evaluation for dementia and a hemoglobin estimation were performed in 605 persons selected by screening a larger community-based sample age 55+ years.

Alzheimer disease with psychosis: excess cognitive impairment is restricted to the misidentification subtype.

Objective: Psychotic symptoms occur in 30%-60% of individuals with Alzheimer disease (AD) with psychosis (AD+P). AD+P identifies a distinct AD phenotype, with increased severity of cognitive impairment and a more rapid cognitive decline. Using factor and cluster analysis, we previously proposed two subtypes of patients with AD+P, one characterized by misidentifications and hallucinations (Misidentification), the other by persecutory delusions (Paranoid).