Embedded Online Questionnaire Measures Are Sensitive to Identifying Mild Cognitive Impairment.

BACKGROUND/AIMS: Early changes in cognitively demanding daily activities occur between normal cognition and the development of mild cognitive impairment (MCI). These real-world functional changes as early signals of cognitive change form a prime target for meaningful early detection of dementia. We examined whether passive aspects of responding to a remotely monitored weekly online questionnaire discriminated between older adults with and without MCI. METHODS: Participants were 83 independent, community-dwelling older adults enrolled in a longitudinal study of in-home monitoring technologies, which included completion of a short weekly online questionnaire of health and life events. RESULTS: In longitudinal analyses, time to complete the online questionnaire decreased over 1 year in both MCI and cognitively intact participants (P<0.01). MCI and intact participants did not differ in the time of day they submitted their questionnaires initially; however, over the course of 1 year MCI participants began to submit their questionnaires progressively later in the day and they needed greater assistance from staff as compared with intact participants (P<0.05). The online questionnaire performance measures were significantly correlated to conventional cognitive test scores (P<0.05) across the spectrum of normal cognition to MCI. CONCLUSIONS: Ambiently assessed, passive performance measures embedded within an online questionnaire are able to discriminate between normal cognition and MCI. Remote monitoring of cognitively demanding routine daily activities is a promising approach for ecologically valid real-world cognitive assessment.

Executive function predicts risk of falls in older adults without balance impairment.

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.

Trajectory of mild cognitive impairment onset.

The objective was to identify the trajectories of onset of memory and other cognitive loss in persons destined to develop mild cognitive impairment (MCI) or dementia. Healthy, community dwelling, cognitively intact elders (n = 156, mean age at entry = 83 years) were examined annually for an average of greater than 7 years. Those who developed at least two consecutive Clinical Dementia Ratings >or= 0.5 were classified as having MCI. Longitudinal mixed effects models with a change point were used to model the aging process in those with and without an MCI diagnosis during follow-up and to model the rate of change relative to the age of onset of MCI. MCI had a preclinical stage of accelerated cognitive loss that was observed 3 to 4 years before the diagnosis of MCI on tests of verbal memory, animal fluency, and visuospatial constructions. Evidence from memory performance before the change point suggests that a slow decline in memory precedes the period of accelerated decline in the development of MCI. Aging transitions leading to MCI and dementia are characterized by unique linear and nonlinear cognitive changes in several domains that precede the diagnosis of MCI and dementia by at least several years.

Physical activity and the risk of dementia in oldest old.

OBJECTIVE: This study evaluated the protective role of physical activity (PA) against cognitive impairment (CI) in the oldest old (age >/= 85). METHOD: Prospective data on 66 optimally healthy, oldest old adults (mean age 88.5) were analyzed using survival analysis. RESULTS: In all, 12 men and 11 women reported exercising > 4 hours per week, and 38 participants developed CI (mean onset age 93; mean follow-up 4.7 years). The effect of exercise was modified by gender. In more active women (> 4 hours/week), the risk of CI was reduced by 88% (95% confidence interval 0.03, 0.41) compared to those less active. Less active women had 2 times the incidence rate of CI compared to less active men and almost 5 times the rate compared to active women. DISCUSSION: This study demonstrates the beneficial effects of exercise on healthy brain aging even in the oldest old and emphasizes the importance of increasing PA in older women.

Cognitive Skills and the Aging Brain: What to Expect.

Whether it's a special episode on the PBS series, "The Secret Life of the Brain" or an entire issue dedicated to the topic in the journal Science, a better understanding of the aging brain is viewed as a key to an improved quality of life in a world where people live longer. Despite dementia and other neurobiological disorders that are associated with aging, improved imaging has revealed that even into our seventies, our brains continue producing new neurons. Our author writes about how mental health functions react to the normal aging process, including why an aging brain may even form the basis for wisdom.

Memory Complaints in Older Adults: Prognostic Value and Stability in Reporting over Time.

OBJECTIVE: The purpose of this longitudinal study was to examine the prognostic value of subjective memory complaints in 156 cognitively intact community-dwelling older adults with a mean age of 83 years. METHODS: Participants were assessed for subjective memory complaints, cognitive performance, functional status, and mood at annual evaluations with a mean follow-up of 4.5 years. RESULTS: Subjective memory complaint at entry (n=24) was not associated with impaired memory performance and did not predict memory decline or progression to incipient dementia. Memory complaints were inconsistent across examinations for 62% of participants who reported memory problems. CONCLUSIONS: Memory complaints by older adults are inconsistent over time. Memory complaint's value as a research criterion for selecting people at risk for dementia is weak among community dwelling older adults. Age, length of follow-up, and other population characteristics may affect the implication of self-reported memory problems.

Computer mouse movement patterns: A potential marker of mild cognitive impairment.

INTRODUCTION: Subtle changes in cognitively demanding activities occur in MCI but are difficult to assess with conventional methods. In an exploratory study, we examined whether patterns of computer mouse movements obtained from routine home computer use discriminated between older adults with and without MCI. METHODS: Participants were 42 cognitively intact and 20 older adults with MCI enrolled in a longitudinal study of in-home monitoring technologies. Mouse pointer movement variables were computed during one week of routine home computer use using algorithms that identified and characterized mouse movements within each computer use session. RESULTS: MCI was associated with making significantly fewer total mouse moves (p<.01), and making mouse movements that were more variable, less efficient, and with longer pauses between movements (p<.05). Mouse movement measures were significantly associated with several cognitive domains (p's<.01-.05). DISCUSSION: Remotely monitored computer mouse movement patterns are a potential early marker of real-world cognitive changes in MCI.

Independent predictors of cognitive decline in healthy elderly persons.

BACKGROUND: Several studies have shown that individually memory, hippocampal volume, and motor measures presage the onset of dementia. It is unclear if these independently contribute to the prediction of mild cognitive impairment. OBJECTIVE: To determine the ability of memory, hippocampal volume, and a gait speed to independently predict cognitive decline in healthy elderly persons. DESIGN: A prospective, longitudinal, observational cohort study with a mean follow-up of 6 years. PARTICIPANTS: One hundred eight optimally healthy elderly cognitively intact subjects. MAIN OUTCOME MEASURES: Any cognitive impairment noted on the Clinical Dementia Rating Scale (score = 0.5) or persistent or progressive cognitive impairment. Cox modeling determined if time to onset of cognitive impairment was associated with baseline logical memory II test score (a measure of delayed recall), hippocampal volume (magnetic resonance imaging), or gait speed (time to walk 30 ft [9 m]) independent of age, sex, depression, or the allele producing the epsilon4 type of apolipoprotein E (APOE epsilon4). RESULTS: Questionable dementia occurred in 48 participants in a mean (SD) of 3.7 (2.4) years. This progressed to persistent cognitive impairment in 38 of these participants in a mean (SD) of 4.4 (2.4) years. Logical memory II test performance and hippocampal volume each predicted onset of questionable dementia, independent of age and sex. Time to walk 30 ft additionally contributed independently to the prediction of time to onset of persistent cognitive impairment. Possessing the APOE epsilon4 allele and depression did not enter either model significantly. CONCLUSIONS: Models combining multiple risk factors should refine the prediction of questionable dementia and persistent cognitive impairment, harbingers of dementia. Individuals at risk for cognitive impairment may represent a high-risk group for intervention.

Neuropathologic basis of age-associated brain atrophy.

IMPORTANCE: While brain volume changes are used as surrogate markers for Alzheimer disease neuropathology in clinical studies, the extent to which these changes are due to pathologic features of Alzheimer disease in the aging brain is not well established. This study aims to clarify the neuropathologic correlates of longitudinal brain atrophy. OBJECTIVE: To examine the association between brain atrophy during life and neuropathology in an elderly population. DESIGN: Autopsy study of a cohort of elderly individuals. SETTING: Community-based population. PARTICIPANTS: Seventy-one healthy elderly individuals were selected from participants of the Oregon Brain Aging Study for having an autopsy, more than 1 magnetic resonance imaging scan, and the last magnetic resonance imaging scan within 36 months of death. MAIN OUTCOMES AND MEASURES: The associations between brain volume trajectories (ventricular, total brain, and hippocampal) and time interaction terms for neurofibrillary tangles, neuritic plaques, gross infarcts, microinfarcts, amyloid angiopathy, Lewy bodies, APOE ε4 presence, and clinical diagnosis (no cognitive impairment, mild cognitive impairment, or dementia as time-varying covariates) were examined in mixed-effects models, adjusting for duration of follow-up and age at death. RESULTS: Ventricular volume trajectory was significantly associated with age, presence of infarcts, neurofibrillary tangle and neuritic plaque scores, APOE ε4 allele presence, and dementia diagnosis. Total brain volume trajectory was significantly associated with age and mild cognitive impairment diagnosis. Hippocampal volume trajectory was significantly associated with amyloid angiopathy. CONCLUSIONS AND RELEVANCE: Ventricular volume trajectory is more sensitive than total brain and hippocampal volume trajectories as a marker of accruing Alzheimer disease and vascular pathology in elderly individuals. The association between brain volume trajectories and cognitive impairment (mild cognitive impairment and dementia) remained after controlling for the degree of neuropathology and other covariates. This suggests that there may be other factors not measured in this study that could be contributing to brain atrophy in those with cognitive impairment.

Neuropathologic basis of white matter hyperintensity accumulation with advanced age.

OBJECTIVE: To determine which vascular pathology measure most strongly correlates with white matter hyperintensity (WMH) accumulation over time, and whether Alzheimer disease (AD) neuropathology correlates with WMH accumulation. METHODS: Sixty-six older persons longitudinally followed as part of an aging study were included for having an autopsy and >1 MRI scan, with last MRI scan within 36 months of death. Mixed-effects models were used to examine the associations between longitudinal WMH accumulation and the following neuropathologic measures: myelin pallor, arteriolosclerosis, microvascular disease, microinfarcts, lacunar infarcts, large-vessel infarcts, atherosclerosis, neurofibrillary tangle rating, and neuritic plaque score. Each measure was included one at a time in the model, adjusted for duration of follow-up and age at death. A final model included measures showing an association with p < 0.1. RESULTS: Mean age at death was 94.5 years (5.5 SD). In the final mixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increased WMH accumulation over time. In post hoc analysis, we found that those with Braak score 5 or 6 were more likely to also have high atherosclerosis present compared with those with Braak score 1 or 2 (p = 0.003). CONCLUSION: Accumulating white matter changes in advanced age are likely driven by small-vessel ischemic disease. Additionally, these results suggest a link between AD pathology and white matter integrity disruption. This may be due to wallerian degeneration secondary to neurodegenerative changes. Alternatively, a shared mechanism, for example ischemia, may lead to both vascular brain injury and neurodegenerative changes of AD. The observed correlation between atherosclerosis and AD pathology supports the latter.

Plasma omega-3 PUFA and white matter mediated executive decline in older adults.

INTRODUCTION: Cross-sectional studies have identified long chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid 20:5n-3 and docosahexaenoic acid 22:6n-3 (O3PUFA) in association with fewer white matter lesions and better executive function in older adults. We hypothesized that O3PUFA are associated with less executive decline over time and that total white matter hyperintensity volume (WMH) mediates this association. METHODS: Eighty-six non-demented older adults were followed over 4 years after measurement of plasma O3PUFA with annual evaluations of cognitive function. A subset of these participants also had brain MRI of total WMH available to conduct a formal mediation analysis of a putative relationship between O3PUFA and cognitive function. RESULTS: Mean age at baseline was 86, 62% were female and 11% carried the APOE4 allele. Each 100 µg/ml increase in plasma O3PUFA associated with 4 s less change in executive decline per year of aging (p = 0.02, fully adjusted model). O3PUFA was not associated with verbal memory or global cognitive changes. The significance of the association between O3PUFA and better executive function was lost once WMH was added to the regression model. CONCLUSION: Executive decline with age appears to be a cognitive domain particularly sensitive to plasma O3PUFA in longitudinal examination. O3PUFA may modulate executive functioning by mechanisms underlying the development of WMH, a biologically plausible hypothesis that warrants further investigation.

Serial position effects in mild cognitive impairment.

Mild cognitive impairment (MCI) is often associated with the preclinical phase of Alzheimer's disease (AD). Special scoring of word-list recall data for serial position has been suggested to improve discrimination of normal aging from dementia. We examined serial position effects in word-list recall for MCI participants compared to Alzheimer patients and controls. Individuals with MCI, like Alzheimer patients, had a diminished primacy effect in recalling words from a list. No alternative scoring system was better than standard scoring of word-list recall in distinguishing MCI patients from controls. Retention weighted scoring improved the discrimination of MCI and AD groups.

Cognitive impairment risk: white matter hyperintensity progression matters.

OBJECTIVE: To determine whether white matter hyperintensity (WMH) progression rate is a better predictor of cognitive impairment risk than baseline WMH volume in healthy elderly individuals. METHOD: Ninety-eight cognitively intact elderly subjects were followed in the Oregon Brain Aging Study. Forty-nine had at least 3 brain MRIs and annual cognitive and neurologic assessments until diagnosed with persistent cognitive impairment (PCI). Brain, ventricular CSF (vCSF), intracranial volume (ICV), hippocampus, total WMH, periventricular (PV) WMH, and subcortical WMH volumes were measured. Cox proportional hazards survival analyses were used to assess cognitive impairment risk. RESULTS: After adjusting for age, apolipoprotein E4 status, incident hypertension, ICV, entry Mini-Mental State Examination, baseline hippocampus, and both baseline vCSF volume and rate of vCSF volume change, increased progression of total WMH volume (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.3-2.7, p = 0.0007) and PV WMH volume (HR 1.94, 95% CI 1.3-3.1, p = 0.001) conferred higher risk of PCI, whereas baseline WMH volumes did not. Every 1 mL/y increase in PV WMH volume was associated with a 94% increased risk of PCI. CONCLUSION: Progression of total and periventricular (PV) white matter hyperintensity (WMH) volumes are better predictors of persistent cognitive impairment (PCI) than baseline WMH burden. Greater PV WMH burden progression is associated with the development of PCI, a potential precursor to Alzheimer or vascular dementia. Identification of factors that decrease WMH accumulation over time is needed to maintain cognitive health in our growing elderly population.

Wechsler Memory Scale-III Faces test performance in patients with mild cognitive impairment and mild Alzheimer's disease.

Little is known about the sensitivity of the Wechsler Memory Scale-Third Edition (WMS-III) Faces subtest to memory impairment associated with mild cognitive impairment (MCI). In this study, Faces performance was examined in 24 MCI patients, 46 mild Alzheimer's disease (AD) patients, and 98 elderly controls. We hypothesized that participants with diagnoses of MCI or AD would be impaired relative to controls on Faces. Analyses showed that AD participants performed significantly worse than MCI and intact participants, although there were no significant differences between MCI and intact participants. Data suggest that brain areas specialized for face recognition memory may be less affected by MCI and mild AD than regions specialized for verbal memory.