Changes in Cognitive Performance Are Associated with Changes in Sleep in Older Adults With Insomnia.

The present study examined sleep features associated with cognition in older adults and examined whether sleep changes following insomnia treatment were associated with cognitive improvements. Polysomnography and cognition (recall, working memory, and reasoning) were assessed before and after an insomnia intervention (Brief Behavioral Treatment of Insomnia [BBTI] or information control [IC]) in 77 older adults with insomnia. Baseline wake-after-sleep-onset (WASO) was associated with recall. Greater NREM (nonrapid eye movement) delta power and lower NREM sigma power were associated with greater working memory and reasoning. The insomnia intervention did not improve performance. However, increased absolute delta power and decreased relative sigma power were associated with improved reasoning. Findings suggest that improvements in executive function may occur with changes in NREM architecture.

Subjective Cognitive Complaints, Personality and Brain Amyloid-beta in Cognitively Normal Older Adults.

OBJECTIVE: Subjective cognitive complaints in otherwise normal aging are common but may be associated with preclinical Alzheimer disease in some individuals. Little is known about who is mostly likely to show associations between cognitive complaints and preclinical Alzheimer pathology. We sought to demonstrate associations between subjective complaints and brain amyloid-ß in cognitively normal older adults; and to explore personality factors as potential moderators of this association. DESIGN: Cross-sectional observational study. SETTING: Clinical neuroimaging research center. PARTICIPANTS: Community volunteer sample of 92 healthy older adults, screened for normal cognition with comprehensive neuropsychological evaluation. MEASUREMENTS: Subjective cognitive self-report measures included the Memory Functioning Questionnaire (MFQ), Cognitive Failures Questionnaire, and the Subjective Cognitive Complaint Scale. Personality was measured with the NEO Five Factor Inventory. Brain amyloid-ß deposition was assessed with Pittsburgh compound B (PiB)-PET imaging. RESULTS: One of three cognitive complaint measures, the MFQ, was associated with global PiB retention (standardized beta = -0.230, p = 0.046, adjusting for age, sex and depressive symptoms). Neuroticism moderated this association such that only high neuroticism individuals showed the predicted pattern of high complaint-high amyloid-ß association. CONCLUSION: Evidence for association between subjective cognition and brain amyloid-ß deposition in healthy older adults is demonstrable but measure-specific. Neuroticism may moderate the MFQ-amyloid-ß association such that it is observed in the context of higher trait neuroticism. Subjective cognitive complaints and neuroticism may reflect a common susceptibility toward psychological distress and negative affect, which are in turn risk factors for cognitive decline in aging and incident Alzheimer disease.

Classification of amyloid-positivity in controls: comparison of visual read and quantitative approaches.

UNLABELLED: An important research application of amyloid imaging with positron emission tomography (PET) is detection of the earliest evidence of fibrillar amyloid-beta (Aß) deposition. Use of amyloid PET for this purpose, requires a reproducible method for defining a cutoff that separates individuals with no significant Aß deposition from those in which Aß deposition has begun. We previously reported the iterative outlier approach (IO) for the analysis of Pittsburgh Compound-B (PiB) PET data. Developments in amyloid imaging since the initial report of IO have led us to re-examine the generalizability of this method. IO was developed using full-dynamic atrophy-corrected PiB PET data obtained from a group of control subjects with a fairly distinct separation between PiB-positive [PiB(+)] and PiB-negative [PiB(-)] subjects. METHODS: We tested the performance of IO using late-summed tissue ratio data with atrophy correction or with an automated template method without atrophy correction and tested the robustness of the method when applied to a cohort of older subjects in which separation between PiB(+) and PiB(-) subjects was not so distinct. RESULTS: The IO method did not perform consistently across analyses and performed particularly poorly when separation was less clear. We found that a sparse k-means (SKM) cluster analysis approach performed significantly better; performing more consistently across methods and subject cohorts. We also compared SKM to a consensus visual read approach and found very good correspondence. CONCLUSION: The visual read and SKM methods, applied together, may optimize the identification of early Aß deposition. These methods have the potential to provide a standard approach to the detection of PiB-positivity that is generalizable across centers.

Postural adjustment errors reveal deficits in inhibition during lateral step initiation in older adults.

Postural dual-task studies have demonstrated effects of various executive function components on gait and postural control in older adults. The purpose of the study was to explore the role of inhibition during lateral step initiation. Forty older adults participated (range 70-94 yr). Subjects stepped to the left or right in response to congruous and incongruous visual cues that consisted of left and right arrows appearing on left or right sides of a monitor. The timing of postural adjustments was identified by inflection points in the vertical ground reaction forces (VGRF) measured separately under each foot. Step responses could be classified into preferred and nonpreferred step behavior based on the number of postural adjustments that were made. Delays in onset of the first postural adjustment (PA1) and liftoff (LO) of the step leg during preferred steps progressively increased among the simple, choice, congruous, and incongruous tasks, indicating interference in processing the relevant visuospatial cue. Incongruous cues induced subjects to make more postural adjustments than they typically would (i.e., nonpreferred steps), representing errors in selection of the appropriate motor program. During these nonpreferred steps, the onset of the PA1 was earlier than during the preferred steps, indicating a failure to inhibit an inappropriate initial postural adjustment. The functional consequence of the additional postural adjustments was a delay in the LO compared with steps in which they did not make an error. These results suggest that deficits in inhibitory function may detrimentally affect step decision processing, by delaying voluntary step responses.

Contributions of cognitive function to straight- and curved-path walking in older adults.

OBJECTIVE: To determine whether the cognitive function contribution to straight- and curved-path walking differs for older adults. DESIGN: Cross-sectional observational study. SETTING: Ambulatory clinical research training center. PARTICIPANTS: People (N=106) aged 65 to 92 years, able to walk household distances independently with or without an assistive device, and who scored 24 or greater on the Mini-Mental State Examination. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Cognitive function was assessed using the Digit Symbol Substitution Test (DSST) as a measure of psychomotor speed, and Trail Making Test Parts A and B (TMT-A and TMT-B) and the Trail Making Test difference score (TMT-B-A) as executive function measures of complex visual scanning and set shifting. Gait speed recorded over an instrumented walkway was used as the measure of straight-path walking. Curved-path walking was assessed using the Figure-of-8 Walk Test (F8W) and recorded as the total time and number of steps for completion. RESULTS: Both DSST and TMT-A independently contributed to usual gait speed (P<.001). TMT-A performance contributed to F8W time (P<.001). Neither TMT-B nor TMT-B-A contributed to usual gait speed or time to complete the F8W. For the number of steps taken to complete the F8W, TMT-A, TMT-B, and TMT-B-A (all P<.001) were independent contributors, while DSST performance was not. CONCLUSIONS: Curved-path walking, as measured by the F8W, involves different cognitive processes compared with straight-path walking. Cognitive flexibility and set-shifting processes uniquely contributed to how individuals navigated curved paths. The measure of curved-path walking provides different and meaningful information about daily life walking ability than usual gait speed alone.

Cognitive slowing associated with elevated serum anticholinergic activity in older individuals is decreased by caffeine use.

OBJECTIVES: This study examined whether some of the age-associated decrements in basic cognitive resources (information-processing speed and working memory) result from anticholinergic medication use (as measured by serum anticholinergic activity [SAA]) and whether such decrements are lessened by caffeine. DESIGN: Cross-sectional observational study. SETTING: University medical center. PARTICIPANTS: One hundred fifty-two normal-elderly community volunteers. MEASUREMENTS: Two tests each of information-processing speed and of working memory were administered, and blood samples were drawn before and after cognitive testing to determine serum levels of anticholinergic activity and of paraxanthine-a caffeine metabolite. RESULTS: Elevated SAA was associated with a significant but modest slowing in information-processing time but only in those individuals who had low levels of serum paraxanthine. SAA did not correlate with performance on tests of working memory. CONCLUSIONS: These results suggest that anticholinergic medications are a relatively minor contributor to the decrements in basic processing resources commonly found in studies of normal aging.

Detecting age differences in resistance to perceptual and motor interference.

The authors asked whether different forms of inhibition are altered differently by aging using a Motor and Perceptual Inhibition Test (MAPIT) based on Nassauer and Halperin (Nassauer & Halperin, 2003, Journal of the International Neuropsychological Society, 9, 25-30). Ninety-eight individuals participating in studies of balance and attention were separated into younger (mean age 25 years) and older (mean age 73) participants. Older participants showed less perceptual and motor inhibition than younger participants, with moderation of this effect by gender, that is, motor inhibition appeared to decline more sharply with age in women than in men. The two scores were uncorrelated in the young but significantly correlated in the older group. Overall, the MAPIT appeared to yield reliable measures of two aspects of inhibition that demonstrate a differential impact of age.

Basal cerebral metabolism may modulate the cognitive effects of Abeta in mild cognitive impairment: an example of brain reserve.

Inverse correlations between amyloid-beta (Abeta) load measured by Pittsburgh Compound-B (PiB) positron emission tomography (PET) and cerebral metabolism using [(18)F]fluoro-2-deoxy-d-glucose (FDG) in Alzheimer's disease (AD) patients, suggest local Abeta-induced metabolic insults. However, this relationship has not been well studied in mild cognitive impairment (MCI) or amyloid-positive controls. Here, we explored associations of Abeta deposition with metabolism via both region-of-interest-based and voxel-based analyses in amyloid-positive control subjects and patients with MCI or AD. Metabolism in parietal and precuneus cortices of AD patients was negatively correlated with PiB retention locally, and more distantly with PiB retention in frontal cortex. In amyloid-positive controls, no clear patterns in correlations were observed. In MCI patients, there were essentially no significant, negative correlations, but there were frequent significant positive correlations between metabolism and PiB retention. Metabolism in anterior cingulate showed positive correlations with PiB in most brain areas in MCI, and metabolism and PiB retention were positively correlated locally in precuneus/parietal cortex. However, there was no significant increase in metabolism in MCI compared to age-matched controls, negating the possibility that Abeta deposition directly caused reactive hypermetabolism. This suggests that, in MCI, higher basal metabolism could either be exacerbating Abeta deposition or increasing the level of Abeta necessary for cognitive impairment sufficient for the clinical diagnosis of AD. Only after extensive Abeta deposition has been present for longer periods of time does Abeta become the driving force for decreased metabolism in clinical AD and, only in more vulnerable brain regions such as parietal and precuneus cortices.

Protecting sleep, promoting health in later life: a randomized clinical trial.

OBJECTIVES: To determine in healthy people aged > or = 75 years 1) if restricting time in bed and education in health sleep practices are superior to an attention-only control condition (i.e., education in healthy dietary practices) for maintaining or enhancing sleep continuity and depth over 2.5 years; and 2) if maintenance or enhancement of sleep continuity and depth promotes the maintenance or enhancement of health-related quality of life. METHODS: Single-blind, randomized, clinical trial in a university-based sleep center, enrolling 64 adults (n = 30 women, 34 men; mean age = 79 years) without sleep/wake complaints (e.g., insomnia or daytime sleepiness), followed by randomized assignment to either: 1) restriction of time in bed by delaying bedtime 30 minutes nightly for 18 months, together with education in healthy sleep practices (SLEEP); or 2) attention-only control condition with education in health dietary practices (NUTRITION). RESULTS: SLEEP did not enhance sleep continuity or depth; however, compared with NUTRITION, SLEEP was associated with decreased time spent asleep (about 30 minutes nightly over 18 months). Contrary to hypothesis, participants in SLEEP reported a decrement in physical health-related quality of life and an increase in medical burden (cardiovascular illness), relative to NUTRITION. Neither markers of inflammation, body mass index, or exercise explained treatment-related changes in medical burden. CONCLUSIONS: Although we cannot exclude a positive effect of education in healthy nutrition, for healthy elderly >75 years of age without sleep complaints, reducing sleep time may be detrimental, whereas allowing more time to sleep (about 7.5 hours nightly) is associated with better maintenance of physical health-related quality of life and stability of medical illness burden over 30 months.

Serum anticholinergic activity and motor performance in elderly persons.

BACKGROUND: Medications prescribed to elderly persons often have an anticholinergic effect, as do many commonly used over-the-counter drugs. Anticholinergic medications are known to produce psychomotor slowing, especially in older persons. METHODS: The present study examined whether the cumulative anticholinergic load present in the serum of community volunteers was associated with decrements on tests of psychomotor performance (gait speed and simple manual response time) known to predict falls in elderly persons. RESULTS: Serum anticholinergic activity (SAA) was relatively low in this group; however, an elevated SAA was associated with a significant slowing in both gait speed and simple response time. CONCLUSION: Cumulative anticholinergic burden may be one of the factors contributing to an increased risk of falls in the older population.

Cerebral Amyloid Deposition and Dual-Tasking in Cognitively Normal, Mobility Unimpaired Older Adults.

Background: We examined relationships between cerebral amyloid-beta (Aß) and cognitive-gait dual-task performance in 27 cognitively normal, mobility unimpaired elders. Methods: We assessed Aß on Pittsburgh Compound B (PiB)-PET. We measured gait speed separately and while performing working-memory, response-inhibition, motor-sequencing, and phone-dialing tasks. We compared dual-task costs on gait and cognitive performance in high-Aß (PiB(+)) and low-Aß (PiB(-)) groups and examined the association between Aß and dual-task performance decrements. Results: PiB(+) (n = 16) were comparable with the PiB(-) (n = 11) individuals on demographics, general cognitive and physical performance, and key brain MRI characteristics. PiB(+) group demonstrated greater dual-task costs on gait speed on all cognitive tasks (p < .05) except on response inhibition. Dual-task costs on cognition were similar between groups. Overall, Aß was associated with dual-task decrement on gait speed but not on dual-task decrement on cognitive performance. Conclusions: Preliminary evidence indicates that cerebral Aß is associated with gait slowing on dual-tasking in healthy older adults.

The relation of white matter hyperintensities to cognitive performance in the normal old: education matters.

This study examined whether the severity of cerebral white matter abnormalities (evident on MR images as white matter hyperintensities (WMH)) was related to the cognitive performance of 141 high-functioning older adults. The elderly showed the typical age decrement on measures of processing speed, working memory, and inhibition; however WMH severity was significantly related only to processing speed. The strength of this relationship was, however, influenced by the educational level of the participants, such that processing speed was more associated with WMH severity in less-educated than in well-educated participants. This is consistent with recent concepts of cognitive reserve, but does raise a question as to the underlying source of the cognitive decrement found in the sort of well-educated elders typically used in cognitive-aging studies.

The nature and determinants of neuropsychological functioning in late-life depression.

CONTEXT: Cognitive impairment in late-life depression (LLD) is highly prevalent, disabling, poorly understood, and likely related to long-term outcome. OBJECTIVES: To determine the characteristics and determinants of neuropsychological functioning LLD. DESIGN: Cross-sectional study of groups of LLD patients and control subjects. SETTING: Outpatient, university-based depression research clinic. PARTICIPANTS: One hundred patients without dementia 60 years and older who met DSM-IV criteria for current episode of unipolar major depression (nonpsychotic) and 40 nondepressed, age- and education-equated control subjects. MAIN OUTCOME MEASURES: A comprehensive neuropsychological battery. RESULTS: Relative to control subjects, LLD patients performed poorer in all cognitive domains. More than half exhibited significant impairment (performance below the 10th percentile of the control group). Information processing speed and visuospatial and executive abilities were the most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing (beta =.45-.80). Education (beta =.32) and ventricular atrophy (beta =.28) made additional modest contributions to variance in measures of language ability. Medical and vascular disease burden, apolipoprotein E genotype, and serum anticholinergicity did not contribute to variance in any cognitive domain. CONCLUSIONS: Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.

Persistence of cognitive impairment in geriatric patients following antidepressant treatment: a randomized, double-blind clinical trial with nortriptyline and paroxetine.

Cognitive dysfunction is common in older persons suffering from a major depression. However, the degree to which this dysfunction is reversible with successful treatment of the depression remains uncertain. The present study examined the effects that treatment (randomized double-blind design) with either an SSRI (paroxetine) or a tricyclic antidepressant (nortriptyline) had on cognition in older depressed patients. The patients' performance was compared to that of a group of normal controls of similar age and education. Patients and controls were administered measures of working memory, information-processing speed, episodic memory and attention five times over the course of a 12 week trial. At baseline, the patients performed more poorly than the elderly controls on all cognitive measures. While the patients' performance did improve over the course of their treatment, the magnitude of this improvement did not exceed that produced in the elderly controls by practice alone. The same pattern of results was evident in both intent-to-treat and responder analyses. Thus, there was no evidence that the depressed patients' cognitive performance normalized after response to antidepressant therapy. Neither the patients' age at onset nor their baseline level of cognitive functioning influenced the amount by which their performance improved over the 12 week trial. There was no difference between paroxetine and nortriptyline in the amount of cognitive change associated with treatment. The present results suggest that cognitive dysfunction persists in older depressed patients even after their mood disorder has responded to antidepressant medications.

Intra-individual variability in gait and in cognitive performance are not related in the elderly.

As humans age, the amount of intra-individual variability (IIV) present in both their gait and their cognitive performance tends to increase. Both gait and cognitive IIV are associated with attentional control and with cerebrovascular disease, suggesting that the IIV in gait and cognitive function should be strongly correlated in the elderly. In this study temporal gait variability was determined from a 60-second period of walking. Cognitive variability was determined from two decision-time tasks assessing inhibition. Despite the presence of substantial amounts of gait and cognitive IIV in 71 elderly individuals, there were no significant correlations between measures of cognitive and gait IIV, suggesting that different factors drive IIV in the motor and cognitive performance of older individuals. These results are not consistent with the common cause theory of aging, which predicts that cognitive and sensorimotor performance should show related declines due to age-related disruption of a common neurological substrate.

Cognitive aging in persons with minimal amyloid-ß and white matter hyperintensities.

Substantial individual differences exist in the magnitude of the cognitive decline associated with normal aging. Potential contributors to this intersubject variability include white matter hyperintensities (WMH) and preclinical Alzheimer's disease, evident as increased brain amyloid. This study examined whether older individuals with minimal evidence of WMH and/or brain amyloid-beta (seen on positron emission tomography with the Pittsburgh compound B radiotracer-PiB) still showed significant cognitive decrements compared to the young. Older individuals, conservatively screened for normal range performance on an extensive neuropsychological battery, underwent structural magnetic resonance imaging (MRI) and PiB scans and performed tests of information processing speed, working memory and inhibitory function. The elderly were divided into PiB(+) and PiB(-) groups based on radiotracer retention. There were no significant differences in cognitive performance between PiB(+) and PiB(-) elderly. However, both PiB groups performed significantly worse than did the young on cognitive testing. WMH burden in the same individuals was quantified by consensus ratings using a 10 point scale with a median split defining two groups, WMH(+) and WMH(-). There were no differences in cognitive performance between WMH(+) and WMH(-) individuals, but both WMH groups performed significantly worse than did the young. Older participants who were both PiB(-) and WMH(-) also performed significantly worse than did the young in all three cognitive domains. The present results suggest that normal-elderly individuals whose brain scans show minimal evidence of amyloid deposition or WMH, still demonstrate a major decrement in comparison to younger persons on measures of processing resources and inhibitory efficiency.

The greater sensitivity of elderly APOE ε4 carriers to anticholinergic medications is independent of cerebrovascular disease risk.

BACKGROUND: Recent studies found use of anticholinergic medications to be associated with greater performance decrements in older persons who carry an ε4 allele of the apolipoprotein E (APOE) gene than in those carrying only ε2 or ε3 alleles. OBJECTIVES: The present study examined whether the apparently greater behavioral toxicity of anticholinergic drugs in ε4 carriers may result from an increased risk of cerebrovascular disease, which is more common in ε4 carriers. METHODS: Cross-sectional data were available from 240 elderly community volunteers who had participated in 2 different studies of the cognitive and motor effects of normal aging. As part of these studies, information was gathered on subjects' use of anticholinergic medications (based on an inventory of medications taken within 24 hours of testing), risk of cerebrovascular disease (Framingham Stroke Risk Profile), and APOE genotype. Performance data were also available from measures of general cognitive status (Mini-Mental State Examination), executive function (Trail Making Test), mood (Geriatric Depression Scale), sleep (Pittsburgh Sleep Quality Index), and walking speed. Logistic and linear regression models were used to examine how outcomes differed between genotypes and drug use, independent of the risk of cerebrovascular disease. RESULTS: In persons with a non-ε4 genotype, anticholinergic medication use did not significantly affect any of the behavioral measures. By contrast, among ε4 carriers, those taking anticholinergic drugs performed significantly worse than did those not taking such drugs on tests of general cognitive status, executive function, mood, and sleep. Adjusting for participants' stroke risk had a minimal effect on these results. CONCLUSIONS: Anticholinergic medication use was associated with poorer performance on measures of cognition, sleep, and mood only in older persons who carried 1 or more ε4 alleles of the APOE gene; this effect did not appear to be the result of an increased risk of cerebrovascular disease.

Inhibitory processes relate differently to balance/reaction time dual tasks in young and older adults.

Inhibitory processes have been suggested to be involved in maintaining balance in older adults, specifically in the integration of sensory information. This study investigated the association between inhibition and the ability to shift attention between auditory and visual modalities during a balance challenge. Young (21-35 years; n = 24) and older (70-85 years; n = 22) healthy subjects completed tasks assessing perceptual inhibition and motor inhibition. Subjects then performed dual-task paradigms pairing auditory and visual choice reaction time tasks with different postural conditions. Sensory channel switch cost was quantified as the difference between visual and auditory reaction times. Results showed that better perceptual and motor inhibition capabilities were associated with less sensory switch cost in the old (perceptual inhibition: r = .51; motor inhibition: r = .48). In the young, neither perceptual nor motor inhibition was associated with sensory switch cost. Inhibitory skills appear particularly important in the elderly for processing events from multiple sensory channels while maintaining balance.

Perceptual inhibition is associated with sensory integration in standing postural control among older adults.

In older adults, maintaining balance and processing information typically interfere with each other, suggesting that executive functions may be engaged for both. We investigated associations between measures of inhibitory processes and standing postural control in healthy young and older adults. Perceptual and motor inhibition was measured using a protocol adapted from Nassauer and Halperin (2003, Dissociation of perceptual and motor inhibition processes through the use of novel computerized conflict tasks. Journal of the International Neuropsychological Society, 9, 25-30). These measures were then correlated to postural sway during standing conditions that required resolving various levels of sensory conflict, for example, world-fixed versus sway-referenced floor and visual scene. In the older adults, perceptual inhibition was positively correlated with sway amplitude on a sway-referenced floor and with a fixed visual scene (r = .68, p < .001). Motor inhibition was not correlated with sway on either group. Perceptual inhibition may be a component of the sensory integration process important for maintaining balance in older adults.

Self-reported sleep quality predicts poor cognitive performance in healthy older adults.

This study examined the relation between sleep quality and cognitive performance in older adults, controlling for common medical comorbidities. Participants were community volunteers who, while not selected on the basis of their sleep, did report substantial variability in sleep quality. Good and poor sleepers differed on tests of working memory, attentional set shifting, and abstract problem solving but not on processing speed, inhibitory function, or episodic memory. Poor sleep was also associated with increased depressive symptomatology but only for functional symptoms (e.g., decreased concentration) and not for mood (e.g., sadness). The relationships between sleep quality and cognition were not explained by confound factors such as cerebrovascular disease, depression, or medication usage. Sleep problems may contribute to performance variability between elderly individuals but only in certain cognitive domains.