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To determine if superior health at old age protects against cognitive impairment (CI) and Alzheimer's disease (AD), we prospectively studied 100 optimally healthy oldest-old (> or =85 years) individuals. Initially, subjects represented the top 3% of the oldest old for health. During 5.6 +/- 0.3 years of follow-up, 34 subjects developed CI, and 23 progressed to AD. By age 100, probability of CI and AD were.65 +/-.09 and.49 +/-.10. Median onset age was 97 years for CI and 100 for AD. Clearly, superior health at old age does not guarantee protection against cognitive decline. Lifetime risks were similar to the general population but onset ages were later, suggesting factors that delay onset are key to improving cognitive health in the elderly. In this population, absence of apolipoprotein E-epsilon4 and male gender were associated with delayed onset, whereas estrogen use and education had no detectable effect on cognitive outcome. [ABSTRACT FROM AUTHOR]

Analyses of eight widely used memory measures (Word List Acquisition and Recall used in the Alzheimer's Disease Assessment Scale and the Consortium to Establish a Registry for Alzheimer's Disease neuropsychology battery, Wechsler Memory Scale-Revised [WMS-R] Logical Memory I and II, WMS-R Visual Reproduction I and II, the memory scores from the Neurobehavioral Cognitive Status Examination [NCSE], memory scores from the Mini-Mental State Examination [MMSE]), and the MMSE total score showed each to have moderate predictive power in differentiating between patients with mild dementia and healthy normal controls. When these instruments were combined in a logistic regression analysis, three of them had substantial predictive power. Together, the Word List Acquisition, WMS-R Logical Memory II, and WMS-R Visual Reproduction II were 97.26% accurate (100% sensitive and 94.59% specific) in distinguishing these two groups. The Word List Acquisition is a brief test that alone had high accuracy (92%). These memory tests are highly useful in the diagnosis of mild dementia. [ABSTRACT FROM AUTHOR]

Study Objective: To test reports that beta blockers, particularly lipophilic forms, impair cognitive function and cause psychiatric disturbances.Design: Randomized, double-blind, controlled crossover trial with eight-week treatment periods.Patients: Sequential sample of 42 male veterans, with untreated diastolic blood pressures (DBP) between 90 and 110 mmHg, aged 35-64 years.Interventions: Propranolol-LA, 80-mg tablets, or atenolol, 50-mg tablets, were given daily, incremented by one tablet at weekly intervals until DBP less than or equal to 90 mmHg. Hydrochlorothiazide was added, if necessary.Main Results: Repeated-measures ANOVA was performed on all cognitive tests. Cognitive test performance was not affected by beta blocker therapy in seven of nine tests and was enhanced on Trail Making Test. Performance was impaired only on Digit Cancellation. Neither Speilberger's State Trait Anxiety Inventory nor the Beck Depression Inventory was affected by either beta blocker.Conclusions: Atenolol or propranolol therapy does not impair cognitive function or contribute significantly to psychiatric side effects. [ABSTRACT FROM AUTHOR]

The parieto-visceral ganglion (PVG) modulates gill habituation, which in turn is mediated by a peripheral neural plexus. [ABSTRACT FROM AUTHOR]

Abstract Background Executive dysfunction has previously been found to be a risk factor for falls. The aim of this study is to investigate the association between executive dysfunction and risk of falling and to determine if this association is independent of balance. Methods Participants were 188 community-dwelling individuals aged 65 and older. All participants underwent baseline and annual evaluations with review of health history, standardized neurologic examination, neuropsychological testing, and qualitative and quantitative assessment of motor function. Falls were recorded prospectively using weekly online health forms. Results During 13 months of follow-up, there were 65 of 188 participants (34.6%) who reported at least one fall. Univariate analysis showed that fallers were more likely to have lower baseline scores in executive function than non-fallers (p = 0.03). Among participants without balance impairment we found that higher executive function z-scores were associated with lower fall counts (p = 0.03) after adjustment for age, sex, health status and prior history of falls using negative binomial regression models. This relationship was not present among participants with poor balance. Conclusions Lower scores on executive function tests are a risk factor for falls in participants with minimal balance impairment. However, this effect is attenuated in individuals with poor balance where physical or more direct motor systems factors may play a greater role in fall risk.

Vascular risk factors for age-related cognitive decline are significant, and their management may ultimately prove the most successful strategy for reducing risk and sustaining cognitive health. This randomized, double-blinded, placebo-controlled trial with parallel group allocation to either marine n-3 polyunsaturated fatty acids (n-3 PUFA) or soybean oil placebo assesses the effects on the total volume of accumulation in cerebral white matter hyperintensities (WMH), a potentially modifiable neurovascular component of age-related cognitive decline. Total WMH accumulation over 3 years is the primary endpoint. The safety and efficacy of n-3 PUFA is evaluated in older adults with significant WMH and suboptimum plasma n-3 PUFA as inclusion criteria. One hundred and two non-demented older adults were enrolled with a mean age of 81.1 (±4.4) years, WMH of 19.4 (±16.1) cm³, and a plasma n-3 PUFA of 86.64 (±29.21) µg/mL. 61% were female, 28% were apolipoprotein E epsilon 4 carriers, and the mean mini-mental state exam (MMSE) was 27.9 (±1.7). This trial provides an initial evaluation of n-3 PUFA effects on WMH, a reproducible and valid risk biomarker for cognitive decline, as well as on inflammatory biomarkers thought to play a role in WMH accumulation. We present the baseline results and operational experience of enriching a study population on advanced age, blood n-3 PUFA, and magnetic resonance imaging (MRI) derived WMH with biomarker outcomes (WMH, inflammation markers) in a dementia prevention paradigm.

Objective: Neuropsychological tests are used for a wide variety of purposes: assessing basic cognitive abilities or disabilities; determining cognitive patterns associated with brain disorders or injury; exploring brain-behavior relationships; and, in some cases, addressing psycho-legal issues. This paper will focus on the limitations of current neuropsychological tests for these purposes., Method: Current limits of neuropsychological tests and assessment procedures are reviewed and recommendations for improvements are made. The relationship between the conceptual basis of neuropsychological tests and modern theories of brain functional organization is discussed. In addition, psycho-legal concerns are briefly outlined., Conclusions: Existing tests and techniques can be improved. Normative data for some neuropsychological tests are based on small samples or have limited validity or reliability data. A variety of neuropsychological tests are available but particular cognitive domains are underrepresented, particularly those involving high-level cognitive skills and social skills. Progress is being made in the availability of tests in multiple languages, but the restricted range of languages and cultural influences demands more attention. Standard test procedures often deviate from real-world activities. In this modern age, some tests have become too familiar because of the Internet. Understanding of complex neural networks activated by cognitive tasks is only beginning to be appreciated. Procedures for determining psycho-legal issues need improvements in some areas.

Background: Understanding contributions of different brain pathologies to domain-specific cognitive trajectories in the oldest old is crucial to guide future intervention studies., Methods: Two-hundred-twenty Oregon Alzheimer's Disease Center research participants who were cognitively intact at entry were followed on average for 7.3 years with annual neuropsychological testing until death (mean age, 93.7 y) and autopsy. Mixed effects models examined the relationship between trajectories in memory, verbal fluency, and mini-mental state examination (MMSE) and pathology (neurofibrillary tangles, neuritic plaques, gross infarcts, hippocampal sclerosis, Lewy bodies, APOE genotype, age at death, and years of education). The association between the MMSE trajectory and pathologic variables were examined using a Poisson model with MMSE errors as outcomes given the nonlinear distribution of MMSE scores., Results: Memory trajectory was associated with the APOε4 allele (P=0.006). Verbal fluency trajectory was associated with gross infarcts (P=0.008). MMSE trajectory was associated with high Braak scores (P=0.03), gross infarcts (P<0.0001), hippocampal sclerosis (P=0.003), moderate neuritic plaques (P=0.04), and the APOε4 allele (P=0.02)., Conclusions: The association between trajectory of decline in global cognitive scores and multiple brain pathologies highlights the importance of accounting for comorbid pathologies in therapeutic trials aimed at one specific pathology in the oldest old. Only the APOε4 allele showed an association with memory decline, despite accounting for Alzheimer's disease pathology, suggesting that APOE may be involved in mechanisms beyond amyloid metabolism in its role in memory. Further studies are needed to examine the role of APOE in brain aging.

The relationship between recent episodes of poor sleep and cognitive testing performance in healthy cognitively intact older adults is not well understood. In this exploratory study we examined the impact of recent sleep disturbance, sleep duration, and sleep variability on cognitive performance in 63 cognitively intact older adults using a novel unobtrusive in-home sensor-based sleep assessment methodology. Specifically, we examined the impact of sleep the night prior, the week prior, and the month prior to a neuropsychological evaluation on cognitive performance. Results showed that mildly disturbed sleep the week prior and month prior to cognitive testing was associated with reduced working memory on cognitive evaluation. One night of mild sleep disturbance was not associated with decreased cognitive performance the next day. Sleep duration was unrelated to cognition. In-home, unobtrusive, sensor monitoring technologies provide a novel method for objective, long-term, and continuous assessment of sleep behavior and other everyday activities that might contribute to decreased or variable cognitive performance in healthy older adults.

Background: Cognitive decline is the cardinal symptom of dementia. Accurate measurement of changes in cognition, while essential for testing interventions to slow cognitive decline, can be challenging in people with dementia (PWD). For example, the laboratory environment may cause anxiety and negatively affect performance., Material and Method: In healthy people, researchers measure one aspect of cognition, attention, via assessing reaction times in a laboratory environment. This repeated-measures study investigated the feasibility of reaction time measurement in participants' homes using the computerized psychomotor vigilance task (PVT) for PWD. Research questions were (a) Can laboratory controls be replicated in the home? (b) Where do PWD perform PVT trials optimally? and (c) What are the preferences of PWD and their caregivers? Two groups that differed by sequence of testing location completed 12 reaction time assessments over 2 days. Caregiver and person with dementia dyad preferences were examined in a follow-up phone interview., Results: Complete data were collected from 14 dyads. Although there were slight differences in lighting between settings, the time of day, temperature, and sound did not differ. There were no significant differences in PVT performance between the two locations, but the group who tested in the home on Day 1 performed better than the group who tested in the lab on Day 1. All participants preferred home examination., Discussion: It is feasible to measure reaction times in the home. Home testing contributes to optimal performance and participants preferred the home.

Objectives: To compare the trajectory of motor decline, as measured by gait speed and finger-tapping speed, between elderly people who developed mild cognitive impairment (MCI) and those who remained cognitively intact. We also sought to determine the approximate time at which the decline in motor function accelerated in persons who developed MCI., Design: Longitudinal cohort study., Participants: Participants were 204 healthy seniors (57.8% women) from the Oregon Brain Aging Study evaluated for up to 20 years using annual neurologic, neuropsychological, and motor examinations., Main Outcome Measures: The pattern of motor decline with aging was compared using a mixed-effects model with an interaction term for age and a clinical diagnosis of MCI. The time before diagnosis of MCI, when the change in gait or finger-tapping speed accelerates, was assessed using a mixed-effects model with a change point for men and women, separately and combined, who developed MCI., Results: The rates of change, with aging, in gait speed (P < .001) and finger-tapping speed in the dominant hand (P = .003) and nondominant hand (P < .001) were significantly different between participants who developed MCI (converters) and those who did not (nonconverters). Using a change point analysis for MCI converters, the decrease in gait speed accelerated by 0.023 m/s/y (P < .001), occurring 12.1 years before the onset of MCI. An acceleration in gait speed decline occurred earlier in men than women. For tapping speed, the change point occurred after the onset of MCI for both dominant and nondominant hands when men and women were combined., Conclusions: Motor decline as indexed by gait speed accelerates up to 12 years before MCI. Longitudinal changes in motor function may be useful in the early detection of dementia during preclinical stages, when the utility of disease-modifying therapies would be greatest.

Background: Early detection of cognitive decline in the elderly has become of heightened importance in parallel with the recent advances in therapeutics. Computerized assessment might be uniquely suited to early detection of changes in cognition in the elderly. We present here a systematic review of the status of computer-based cognitive testing, focusing on detection of cognitive decline in the aging population., Methods: All studies purporting to assess or detect age-related changes in cognition or early dementia/mild cognitive impairment by means of computerized testing were included. Each test battery was rated on availability of normative data, level of evidence for test validity and reliability, comprehensiveness, and usability. All published studies relevant to a particular computerized test were read by a minimum of two reviewers, who completed rating forms containing the above mentioned criteria., Results: Of the 18 test batteries identified from the initial search, 11 were appropriate to cognitive testing in the elderly and were subjected to systematic review. Of those 11, five were either developed specifically for application with the elderly or have been used extensively with that population. Even within the computerized testing genre, great variability existed in manner of administration, ranging from fully examiner-administered to fully self-administered. All tests had at least minimal reliability and validity data, commonly reported in peer-reviewed articles. However, level of rigor of validity testing varied widely., Conclusion: All test batteries exhibited some of the strengths of computerized cognitive testing: standardization of administration and stimulus presentation, accurate measures of response latencies, automated comparison in real time with an individual's prior performance as well as with age-related norms, and efficiencies of staffing and cost. Some, such as the Mild Cognitive Impairment Screen, adapted complicated scoring algorithms to enhance the information gathered from already existing tests. Others, such as CogState, used unique interfaces and subtests. We found that although basic indices of psychometric properties were typically addressed, sufficient variability exists that currently available computerized test batteries must be judged on a case-by-case basis.

Human tests designed to mirror rodent tests of object recognition and spatial navigation were administered to adult cognitively healthy humans. Facial recognition was also assessed. There was no sex difference in facial recognition, consistent with earlier studies. In the object recognition test, the test-retest NINL total scores during the same visit were highly correlated, comparable to the test-retest correlations obtained in the established facial recognition test. There were no effects of sex on object recognition. However, in the spatial navigation test, there were effects of sex on spatial learning and memory during the session with the hidden, but not visible, target. These tests might be useful to compare assessments of object recognition and spatial learning and memory in humans and animal models.

A sample of 33 young-old (ages 65 to 74) and 20 oldest-old (ages 84 to 93) healthy elderly without dementia were assessed with neuropsychological tests annually over a 4-year period to examine longitudinal changes in cognitive functioning. Significant age-group differences existed at baseline in participants' performances on tests of immediate memory and visuospatial skills. There were no age-group differences in the rate of change over the 4-year interval on any neuropsychological tests. Within each age-group, the amount of change over time was minimal for most tests though some practice effects were apparent, and on some tests mild decline was observed. Results suggest that healthy old adults, including the oldest-old, do not experience measurable declines in cognitive functioning over a 4-year period.

Objective: To look for preclinical markers of Alzheimer's dementia in a sample of healthy, oldest old individuals., Design: Prospective, longitudinal study of individuals examined at yearly intervals with neuropsychological tests selected to be sensitive to the early detection of dementia., Participants: One hundred and thirty-nine community-dwelling, functionally independent, healthy individuals 65 to 106 years of age who met strict criteria for lack of dementia at entry. Incident dementia cases consisted of 16 volunteers all 80 years old or older who developed dementia of the Alzheimer's type and 31 volunteers 80 years old and older showing no evidence of dementia during a mean 2.8-year follow-up interval., Measurements: Scores on 10 neuropsychological measures were analyzed for the initial examination when none of the volunteers showed clinical evidence of dementia and for the two subsequent yearly examinations., Results: Individuals who subsequently developed dementia showed evidence of verbal memory impairment at their initial examination, which was a mean of 2.8 years before clinical evidence of dementia. The average yearly incidence rate for dementia in those 80 years of age and older was 12%. Performance of individuals who did not development dementia remained relatively stable during follow-up for up to 5 years., Conclusion: Alzheimer's disease has a preclinical stage in which verbal memory decline is the earliest sign. Dementia in the oldest old is distinguishable from age-related cognitive decline.

The oldest old are the fastest-growing segment of our population and have the highest prevalence of dementia. Little is known about the genetics of cognitive health in the very old. The aim of this study was to determine whether the genetic risk factors for Alzheimer disease (AD)--namely, apolipoprotein E (APOE) epsilon4 allele and a family history of dementia-continue to be important factors in the cognitive health of the very old. Case-control studies suggest that the effect of genetic factors diminishes at age >75 years. The present prospective study provided evidence to the contrary. We studied 114 Caucasian subjects who were physically healthy and cognitively intact at age 75 years and who were followed, for an average of 4 years, with neurological, psychometric, and neuroimaging examinations. Excellent health at entry did not protect against cognitive decline. Incidence of cognitive decline rose sharply with age. epsilon4 and a family history of dementia (independent of epsilon4) were associated with an earlier age at onset of dementia. Subjects who had epsilon4 or a family history of dementia had a ninefold-higher age-specific risk for dementia than did those who had neither epsilon4 nor a family history of dementia. These observations suggest that the rate of cognitive decline increases with age and that APOE and other familial/genetic factors influence the onset age throughout life.

Objective: To evaluate attention deficit in Alzheimer's disease (AD) and its relationship to attention deficits associated with aging and with medications altering alertness., Methods: Ten patients with probable AD, 10 healthy old controls, and 15 young controls performed a covert orienting of spatial attention task. Young controls performed the task an additional time after ingestion of diphenhydramine 1 mg/kg. Reaction times were obtained following valid, neutral, and invalid cues., Results: In all groups, the reaction times were shortest for the validly cued stimuli and longest for the invalidly cued stimuli. Additionally, the AD patients performed disproportionately worse following the invalid cue than did the control groups. Young controls given diphenhydramine had decreased subjective alertness, performed worse than they did before drug but better than the old controls or AD patients, and had no disproportionate impairment with the invalid cue., Conclusions: AD patients have disproportionate problems shifting spatial attention compared with age-matched controls. Impaired attentional performance in AD cannot be simulated in young subjects by ingestion of a combined antihistamine/anticholinergic agent at a dose sufficient to produce significant changes in alertness.

Purpose: To evaluate the utility of a recently reported simple measure of brain atrophy on MR imaging, the interuncal distance (IUD)., Methods: Measurements of the IUD were made over a 12-month interval in 10 patients with probable early Alzheimer disease and in a comparison group of age-matched healthy control subjects. The measurements were made in both the transaxial and coronal planes., Results: Significant group differences for the coronal measurement of IUD were found in both the absolute value of the measurement and the IUD corrected for head size. There was overlap in IUD between the disease and the control groups. These differences were not found for the transaxial IUD. Significant positive correlations of the IUD with Mini-Mental State Examination score and Clinical Dementia Rating Scale stage were observed. Over the age range tested, age was not significantly correlated with IUD in the sample., Conclusions: The interuncal distance (IUD) is not a useful screening measurement for Alzheimer disease.

Study Objective: To test reports that beta blockers, particularly lipophilic forms, impair cognitive function and cause psychiatric disturbances., Design: Randomized, double-blind, controlled crossover trial with eight-week treatment periods., Patients: Sequential sample of 42 male veterans, with untreated diastolic blood pressures (DBP) between 90 and 110 mmHg, aged 35-64 years., Interventions: Propranolol-LA, 80-mg tablets, or atenolol, 50-mg tablets, were given daily, incremented by one tablet at weekly intervals until DBP less than or equal to 90 mmHg. Hydrochlorothiazide was added, if necessary., Main Results: Repeated-measures ANOVA was performed on all cognitive tests. Cognitive test performance was not affected by beta blocker therapy in seven of nine tests and was enhanced on Trail Making Test. Performance was impaired only on Digit Cancellation. Neither Speilberger's State Trait Anxiety Inventory nor the Beck Depression Inventory was affected by either beta blocker., Conclusions: Atenolol or propranolol therapy does not impair cognitive function or contribute significantly to psychiatric side effects.