Optimizing ADAS-Cog Worksheets: A Survey of Clinical Trial Rater s' Perceptions.

Background: The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADASCog) remains the most widely used test of longitudinal cognitive functioning in Alzheimer's disease (AD) clinical trials. Unlike most neuropsychological tests, the ADAS-Cog source documentation worksheets are not uniform across clinical trials, and vary by document layout, inclusion of administration and/or scoring instructions, and documentation of subtest scoring (e.g.

Sex and post-menopause hormone therapy effects on hippocampal volume and verbal memory.

Many studies suggest sex differences in memory and hippocampal size, and that hormone therapy (HT) may positively affect these measures in women; however, the parameters of HT use that most likely confer benefits are debated. We evaluated the impact of sex and postmenopausal HT use on verbal learning and memory and hippocampal size in 94 cognitively intact women and 49 men. Using analysis of covariance that controlled for age and education, women had better total word learning and delayed verbal memory performance than men.

Neuropathological findings of PSP in the elderly without clinical PSP: possible incidental PSP?

Aims: We aimed to describe cases with incidental neuropathological findings of progressive supranuclear palsy (PSP) from the Banner Sun Health Research Institute Brain and Body Donation Program.

Methods: We performed a retrospective review of 277 subjects with longitudinal motor and neuropsychological assessments who came to autopsy. The mean Gallyas-positive PSP features grading for subjects with possible incidental neuropathological PSP was compared to those of subjects with clinically manifest disease.

The Alzheimer's questionnaire: a proof of concept study for a new informant-based dementia assessment.

The aim of this pilot study is to determine the feasibility and clinical utility of a brief, informant-based screening questionnaire for Alzheimer's disease (AD) that can be administered in a primary care setting. The Alzheimer's Questionnaire (AQ) was administered to the informants of 188 patients in 3 dementia clinics (50 cognitively normal, 69 mild cognitive impairment (MCI), 69 AD). Total score for the AQ is based upon the sum of clinical symptom items in which the informant responds as being present.

Cholesterol and cognitive performance in normal controls and the influence of elective statin use after conversion to mild cognitive impairment: results in a clinical trial cohort.

Background: We reported a significant 67% reduction in the hazard risk of incident Alzheimer's disease (AD) with elective statin use in the AD Anti-inflammatory Prevention Trial (ADAPT), without a reduction in risk of incident mild cognitive impairment (MCI).

Objective: To assess if cholesterol levels are associated with cognitive performance and determine if statin use alters cognitive performance after onset of MCI.

Design: Fractionated cholesterol levels, neurological and cognitive status were evaluated annually.

Incidental Lewy body disease: clinical comparison to a control cohort.

Limited clinical information has been published on cases pathologically diagnosed with incidental Lewy body disease (ILBD). Standardized, longitudinal movement and cognitive data was collected on a cohort of subjects enrolled in the Sun Health Research Institute Brain and Body Donation Program. Of 277 autopsied subjects who had antemortem clinical evaluations within the previous 3 years, 76 did not have Parkinson's disease, a related disorder, or dementia of which 15 (20%) had ILBD.

Olfaction in the elderly: a cross-sectional analysis comparing Parkinson's disease with controls and other disorders.

Olfactory dysfunction in Parkinson's disease (PD) is an association that has been well documented in the medical literature, although the underlying pathophysiologic mechanism has not been clearly elucidated. In the Sun Health Research Institute Brain and Body Donation Program, subjects were tested for olfactory function. Olfaction was impaired in subjects with clinically probable PD but not those with essential tremor (ET), restless legs syndrome (RLS), or mild cognitive impairment.

Parkinson disease with dementia: comparing patients with and without Alzheimer pathology.

Subjects with Parkinson disease (PD) frequently develop dementia with greater than one-third meeting neuropathologic diagnostic criteria for Alzheimer disease (AD). The objective is to identify clinical and neuropathologic differences between Parkinson disease with dementia (PDD) subjects, with and without coexistent AD pathology. Neuropathologic examination was available on subjects diagnosed by clinicopathologic criteria with PDD-AD (N=23) and PDD+AD (N=28).

Correlation of clinical features with argyrophilic grains at autopsy.

Argyrophilic grains (AGs) are a pathologic feature found in association with neurodegenerative disease. Some have suggested that these features may occur as a distinctive condition. We reviewed 80 subjects from our tissue bank with pathologically confirmed AGs and identified their clinical features.

No evidence for cognitive dysfunction or depression in patients with mild restless legs syndrome.

Restless legs syndrome is a common disorder that may interrupt sleep and has been reported to produce daytime fatigue and/or mood changes. This study assessed whether patients with RLS have more cognitive dysfunction and depression than individuals of the same age and education who do not have RLS. The study showed that older individuals with mild RLS for at least 1 year do not have cognitive dysfunction and are not depressed compared with a control group of similar age and education.

Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect.

Background: The APOE epsilon4 allele is associated with the risk of late-onset Alzheimer's disease. The age at which memory decline diverges among persons who are homozygous for the APOE epsilon4 allele, those who are heterozygous for the allele, and noncarriers is unknown.

Methods: Using local advertisements, we recruited cognitively normal subjects between the ages of 21 and 97 years, who were grouped according to their APOE epsilon4 status.

Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction.

The two current major staging systems in use for Lewy body disorders fail to classify up to 50% of subjects. Both systems do not allow for large numbers of subjects who have Lewy-type alpha-synucleinopathy (LTS) confined to the olfactory bulb or who pass through a limbic-predominant pathway that at least initially bypasses the brainstem. The results of the current study, based on examination of a standard set of ten brain regions from 417 subjects stained immunohistochemically for alpha-synuclein, suggest a new staging system that, in this study, allows for the classification of all subjects with Lewy body disorders.

Possible Alzheimer's disease in an apolipoprotein E2 homozygote.

The objective of this study was to describe a case of Alzheimer's disease in an ApoE epsilon2/epsilon2 homozygote. ApoE epsilon2/epsilon2 is the rarest of the apolipoprotein E genotypes, representing only 1.4% of the population.

Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease.

Objectives: Patients with Alzheimer dementia often display both agitated behavior and poor sleep. Given that the disease is often associated with low endogenous levels of melatonin, exogenous melatonin administration may lead to improvements in sleep and agitation.

Design: Randomized, placebo-controlled study.

Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease.

Background: We evaluated the amounts of amyloid beta (Abeta)) peptides in the central nervous system (CNS) and in reservoirs outside the CNS and their potential impact on Abeta plasma levels and Alzheimer's disease (AD) pathology.

Methods: Amyloid beta levels were measured in (1) the plasma of AD and nondemented (ND) controls in a longitudinal study, (2) the plasma of a cohort of AD patients receiving a cholinesterase inhibitor, and (3) the skeletal muscle, liver, aorta, platelets, leptomeningeal arteries, and in gray and white matter of AD and ND control subjects.

Results: Plasma Abeta levels fluctuated over time and among individuals, suggesting continuous contributions from brain and peripheral tissues and associations with reactive circulating proteins.

Comment on administration and scoring of the Neuropsychiatric Inventory in clinical trials.

Background: The Neuropsychiatric Inventory (NPI) is commonly used in dementia trials to quantify and qualitate changes in psychiatric symptoms.

Methods: A questionnaire was administered to clinical trial raters to assess whether they were being trained to administer and score the NPI differently between clinical trial protocols.

Results: Responses to the survey indicated that there are differences between clinical trials protocols in how the instrument is administered and scored.

Administration and scoring variance on the ADAS-Cog.

The Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) is the most commonly used primary outcome instrument in clinical trials for treatments of dementia. Variations in forms, administration procedures and scoring rules, along with rater turnover and intra-rater drift may decrease the reliability of the instrument. A survey of possible variations in the ADAS-Cog was administered to 26 volunteer raters at a clinical trials meeting.

Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders.

Involvement of the olfactory bulb by Lewy-type alpha-synucleinopathy (LTS) is known to occur at an early stage of Parkinson's disease (PD) and Lewy body disorders and is therefore of potential usefulness diagnostically. An accurate estimate of the specificity and sensitivity of this change has not previously been available. We performed immunohistochemical alpha-synuclein staining of the olfactory bulb in 328 deceased individuals.

Reduced risk of incident AD with elective statin use in a clinical trial cohort.

Statins have been reported to reduce the risk and be of benefit in the treatment of Alzheimer's disease (AD). Individuals enrolling in the randomized controlled trial testing two anti-inflammatory agents for primary prevention of AD (Alzheimer's Disease Anti-inflammatory Prevention Trial; ADAPT) were allowed the elective use of statins. Our objective was to assess whether statin use is associated with reduced risk of incident AD among ADAPT participants.

Challenges to the recognition and assessment of Alzheimer's disease in American Indians of the southwestern United States.

Little is known about Alzheimer's disease (AD) and related neurodegenerative diseases in American Indian (AI) populations. To provide appropriate health care to elder AIs, whose population is expected to increase dramatically during the next 50 years, it is imperative to attain a better understanding of the interaction of culture and disease in this underserved population. Raising awareness in the AI population regarding the nature of dementia as it compares to normal aging and the development of culturally appropriate instruments to detect and stage AD are essential for future health care efforts.

Hippocampal volume change in the Alzheimer Disease Cholesterol-Lowering Treatment trial.

Numerous clinical studies suggest a link between elevated cholesterol and increased risk of Alzheimer disease (AD), and the preponderance of data suggests that statin therapy may reduce the risk of AD later in life. The first clinical investigation of statin therapy in patients with AD, the AD Cholesterol-Lowering Treatment (ADCLT) trial, found that atorvastatin 80 mg/day was associated with improvements relative to placebo on some, but not all, cognitive measures after 6 months and 1 year of therapy. We report here findings from a pilot ADCLT substudy showing a nonsignificant reduction in total hippocampal volume with 1 year of atorvastatin therapy compared with placebo, driven by a highly significant reduction in right hippocampal volume with atorvastatin therapy.

The Sun Health Research Institute Brain Donation Program: description and experience, 1987-2007.

The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider.