Red blood cell ω-3 fatty acid levels and markers of accelerated brain aging.

Objective: Higher dietary intake and circulating levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for dementia, but the pathways underlying this association remain unclear. We examined the cross-sectional relation of red blood cell (RBC) fatty acid levels to subclinical imaging and cognitive markers of dementia risk in a middle-aged to elderly community-based cohort.

Methods: We related RBC DHA and EPA levels in dementia-free Framingham Study participants (n = 1575; 854 women, age 67 ± 9 years) to performance on cognitive tests and to volumetric brain MRI, with serial adjustments for age, sex, and education (model A, primary model), additionally for APOE ε4 and plasma homocysteine (model B), and also for physical activity and body mass index (model C), or for traditional vascular risk factors (model D).

Cerebrospinal fluid biomarkers and proximity to diagnosis in preclinical familial Alzheimer's disease.

Background/aims: Biological markers of utility in tracking Alzheimer's disease (AD) during the presymptomatic prodromal phase are important for prevention studies. Changes in cerebrospinal fluid (CSF) levels of 42-amino-acid β-amyloid (Aβ(42)), total tau protein (t-tau) and phosphorylated tau at residue 181 (p-tau(181)) during this state are incompletely characterized.

Methods: We measured CSF markers in 13 carriers of familial AD (FAD) mutations that are fully penetrant for causing AD (PSEN1 and APP) and in 5 non-mutation-carrying family members.

Proteomic changes in cerebrospinal fluid of presymptomatic and affected persons carrying familial Alzheimer disease mutations.

Objective: To identify cerebrospinal fluid (CSF) protein changes in persons who will develop familial Alzheimer disease (FAD) due to PSEN1 and APP mutations, using unbiased proteomics.

Design: We compared proteomic profiles of CSF from individuals with FAD who were mutation carriers (MCs) and related noncarriers (NCs). Abundant proteins were depleted and samples were analyzed using liquid chromatography-electrospray ionization-mass spectrometry on a high-resolution time-of-flight instrument.

Cortical and hippocampal atrophy in patients with autosomal dominant familial Alzheimer's disease.

Background: Both familial and sporadic Alzheimer's disease (AD) result in progressive cortical and subcortical atrophy. Familial autosomal dominant AD (FAD) allows us to study AD brain changes presymptomatically.

Methods: 33 subjects at risk for FAD (25 for PSEN1 and 8 for APP mutations; 22 mutation carriers and 11 controls) and 3 demented PSEN1 mutation carriers underwent T(1)-weighted MPRAGE 1.

Addressing the challenges to successful recruitment and retention in Alzheimer's disease clinical trials.

Among the key challenges in Alzheimer's disease drug development is the timely completion of clinical trials. Unfortunately, clinical trials often suffer from slow or insufficient enrollment. Successful clinical trial recruitment describes a balance between expeditiously achieving full enrollment and ensuring an appropriate study sample.

Increased fMRI signal with age in familial Alzheimer's disease mutation carriers.

Although many Alzheimer's disease (AD) patients have a family history of the disease, it is rarely inherited in a predictable way. Functional magnetic resonance imaging (fMRI) studies of nondemented adults carrying familial AD mutations provide an opportunity to prospectively identify brain differences associated with early AD-related changes. We compared fMRI activity of 18 nondemented autosomal dominant AD mutation carriers with fMRI activity in eight of their noncarrier relatives as they performed a novelty encoding task in which they viewed novel and repeated images.

Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation.

Familial Alzheimer's disease (AD) due to PSEN1 mutations provides an opportunity to examine AD biomarkers in persons in whom the diagnosis is certain. We describe a 55 year-old woman with clinically probable AD and a novel PSEN1 mutation who underwent genetic, clinical, biochemical and magnetic resonance and nuclear imaging assessments. We also describe neuropathological findings in her similarly affected brother.

The use of profanity during letter fluency tasks in frontotemporal dementia and Alzheimer disease.

Objective: To assess whether the production of profanity during letter fluency testing distinguishes frontotemporal dementia (FTD) and Alzheimer disease (AD) patients.

Background: Alterations in language and social behavior typify FTD spectrum disorders. Nonetheless, in can be difficult to distinguish pathologically defined frontotemporal lobar degeneration (FTLD) from AD clinically.

Effects of risk genes on BOLD activation in presymptomatic carriers of familial Alzheimer's disease mutations during a novelty encoding task.

Prior functional magnetic resonance imaging (fMRI) studies have found increased activity-related blood oxygen level-dependent (BOLD) signal in cognitively normal persons at genetic risk for Alzheimer's disease (AD). This has been interpreted as a compensatory response to incipient AD pathology. We studied the effects of fully penetrant familial Alzheimer's disease (FAD) mutations and apolipoprotein E (APOE) genotype on BOLD fMRI during a novelty encoding task in presymptomatic subjects.

Effects of rivastigmine transdermal patch and capsule on aspects of clinical global impression of change in Alzheimer's disease: a retrospective analysis.

Background: The Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale is widely used in Alzheimer trials. It assesses cognition, activities of daily living (ADLs), behavior and global functioning. To advance the understanding of relationships between the ADCS-CGIC and scores from other commonly used tools, this analysis investigated the ability of each domain to measure change.

Integrating ADNI results into Alzheimer's disease drug development programs.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is providing critical new information on biomarkers in cognitively normal elderly, persons with mild cognitive impairment (MCI), and patients with mild Alzheimer's disease (AD). The data provide insights into the progression of the pathology of AD over time, assist in understanding which biomarkers might be most useful in clinical trials, and facilitate development of disease-modifying treatments. ADNI results are intended to support new AD treatment development; this report considers how ADNI information can be integrated in AD drug development programs.

Current therapeutic targets for the treatment of Alzheimer's disease.

Alzheimer's disease is a progressive neurodegenerative disease for which no cure exists. There is a substantial need for new therapies that offer improved symptomatic benefit and disease-slowing capabilities. In recent decades there has been substantial progress in understanding the molecular and cellular changes associated with Alzheimer's disease pathology.

Sertad1 plays an essential role in developmental and pathological neuron death.

Developmental and pathological death of neurons requires activation of a defined pathway of cell cycle proteins. However, it is unclear how this pathway is regulated and whether it is relevant in vivo. A screen for transcripts robustly induced in cultured neurons by DNA damage identified Sertad1, a Cdk4 (cyclin-dependent kinase 4) activator.

Effects of rivastigmine in Alzheimer's disease patients with and without hallucinations.

Hallucinations in Alzheimer's disease (AD) may indicate greater cortical cholinergic deficits. Rivastigmine has shown larger treatment benefits versus placebo in dementia with Lewy bodies and Parkinson's disease dementia patients with hallucinations. In this retrospective, hypothesis-generating analysis, we investigated whether hallucinations in AD were associated with greater treatment benefits with rivastigmine.

Mary S. Easton Center of Alzheimer's Disease Research at UCLA: advancing the therapeutic imperative.

The Mary S. Easton Center for Alzheimer's Disease Research (UCLA-Easton Alzheimer's Center) is committed to the "therapeutic imperative" and is devoted to finding new treatments for Alzheimer's disease (AD) and to developing technologies (biomarkers) to advance that goal. The UCLA-Easton Alzheimer's Center has a continuum of research and research-related activities including basic/foundational studies of peptide interactions; translational studies in transgenic animals and other animal models of AD; clinical research to define the phenotype of AD, characterize familial AD, develop biomarkers, and advance clinical trials; health services and outcomes research; and active education, dissemination, and recruitment activities.

Insensitivity of visual assessment of hippocampal atrophy in familial Alzheimer's disease.

Medial temporal atrophy is a well-established marker for Alzheimer's disease (AD). However, due to normal variation in the size of medial temporal structures and variability in how radiologists interpret images, the use of clinical reads in establishing the presence of pathological atrophy is imprecise. A limitation of studies of magnetic resonance imaging (MRI) measures in AD is diagnostic uncertainty as it can be unknown if pre- or early-symptomatic subjects go on to develop AD and most subjects do not undergo autopsy verification of the diagnosis.

Rivastigmine transdermal patch skin tolerability: results of a 1-year clinical trial in patients with mild-to-moderate Alzheimer's disease.

Background And Objectives: Transdermal patches provide non-invasive, continuous drug delivery, and offer significant potential advantages over oral treatments. With all transdermal treatments a proportion of patients will experience some form of skin reaction. The rivastigmine patch has been approved for the treatment of mild-to-moderate Alzheimer's disease (AD) since July 2007 in the US.

Defining and labeling disease-modifying treatments for Alzheimer's disease.

Alzheimer's disease (AD) might be treated with symptomatic, neuroprotective, or neurorestorative therapies. Neuroprotective and neurorestorative interventions are disease-modifying therapies. Disease modification can be defined as treatments or interventions that affect the underlying pathophysiology of the disease and have a beneficial outcome on the course of AD.

Current concepts of mild cognitive impairment and their applicability to persons at-risk for familial Alzheimer's disease.

The definition of mild cognitive impairment (MCI) as a precursor for Alzheimer's disease (AD) represented an important step forward in diagnosing the illness in its earliest stage. However, diagnoses based principally on cognitive performance have limitations in that there is variability between centers in which tests are employed and in how they are interpreted. Advances in our understanding of imaging and biochemical changes occurring early in the illness have improved our ability to diagnose AD in this early phase and diagnostic criteria for AD have been proposed recently based on such biomarkers.

Commentary on "a roadmap for the prevention of dementia II: Leon Thal Symposium 2008." Prevention trials in persons at risk for dominantly inherited Alzheimer's disease: opportunities and challenges.

Autosomal dominant familial Alzheimer's disease (FAD) of young onset due to alterations in the , , and genes is a fully-penetrant and devastating condition. As the subsequent development of AD in persons inheriting such genes is essentially certain, the condition provides a unique opportunity to perform informative studies of interventions with potential for preventing the disease. Though feasible, there are many challenges to such an endeavor including the fact that most persons at-risk for FAD do not desire to know their genetic status.

Glucagon-like peptide-1 (GLP-1) diminishes neuronal degeneration and death caused by NGF deprivation by suppressing Bim induction.

Glucagon-like peptide-1 (GLP-1) is a glucoincretin hormone most intensively studied for its actions on insulin secreting beta-cells. GLP-1 and its receptor are also found in brain and accumulating evidence indicates that GLP-1 has neuroprotective actions. Here, we investigated whether GLP-1 protects neuronal cells from death evoked by nerve growth factor (NGF) withdrawal.