Diane B. Howieson

Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia

Objective To determine initial locus and rate of degeneration of temporal lobe structures (total lobe, hippocampus and parahippocampus) in preclinical dementia. Background Postmortem studies suggest that the earliest changes in Alzheimers disease are neurofibrillary tangle formation in hippocampus and adjacent cortex. MRI volume analysis of temporal lobe structures over time in subjects prior to developing dementia may allow the identification of when these processes begin, the rate they develop, and which areas are key to symptom development. Methods 30 nondemented (NOD), healthy, elderly individuals enrolled in a prospective study of healthy aging evaluated annually over a mean of 42 months. Twelve subjects with subsequent cognitive decline were assigned to the preclinical dementia group (PreD). All 120 annual MRI studies analyzed by volumetric techniques assessed group differences in temporal lobe volumes and rates of brain loss. Results NOD as well as PreD subjects had significant, time-dependent decreases in hippocampal and parahippocampal volume. Rates of volume loss between the groups did not significantly differ. PreD cases had significantly smaller hippocampi when asymptomatic. Parahippocampal volume did not differ between PreD and NOD cases. Significant time-dependent temporal lobe atrophy was present only in PreD. Conclusions Hippocampal and parahippocampal atrophy occurs at a similar rate regardless of diagnostic group. Those who develop dementia may have smaller hippocampi to begin with, but become symptomatic because of accelerated loss of temporal lobe volume. Temporal lobe volume loss may mark the beginning of the disease process within six years prior to dementia onset.

Talking while walking The effect of a dual task in aging and Alzheimer's disease

We determined the effects of distraction on gait in healthy elderly subjects and Alzheimers disease (AD) patients. The effects of simultaneous performance of a verbal fluency task (effect of reciting male or female names) on the time and number of steps taken to walk 30 feet were compared using a repeated-measures design with between-group comparison between community-dwelling healthy old old (oOld; n = 20; mean age ± SD, 86 ± 4.4), healthy young old (yOld; n = 23; mean age ± SD, 72 ± 3.6), and probable AD subjects without parkinsonism (n = 15; mean age ± SD, 74 ± 13). AD patients slowed more than the yOld (p = 0.005) and the oOld (p = 0.002). The yOld and oOld did not differ from each other (p = 0.68). Mean (±SD) differences in time were as follows: yOld, −2.2 ± 1.9; oOld, −1.6 ± 2.0; AD, −7.1 ± 9.2 seconds. The change in steps did not differ between groups. Walking speed of AD patients slowed more than that of elderly subjects during the dual task. This may contribute to the risk of falls in AD.

Status of computerized cognitive testing in aging: A systematic review

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.

The Trajectory of Gait Speed Preceding Mild Cognitive Impairment

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.

Motor slowing precedes cognitive impairment in the oldest old

Eighty-five healthy elderly subjects were prospectively evaluated for 3 years to determine motor differences between those who remain cognitively intact and those who developed cognitive impairment during prospective follow-up. The 18 subjects who developed cognitive impairment had slower finger tapping and took longer to walk 30 feet before or at the time of cognitive impairment. Coordination was more impaired and steps, but not balance, deteriorated more rapidly, independent of other variables.

Cognitive Markers Preceding Alzheimer's Dementia in the Healthy Oldest Old

OBJECTIVE: To look for preclinical markers of Alzheimers dementia in a sample of healthy, oldest old individuals.

Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline.

Background: White matter hyperintensity (WMH) change on brain MRI is observed with increased frequency in the elderly and has been independently associated with neurologic decline. The degree to which the location and rate of volume increase in WMH affects other structural brain changes along with cognitive and motor performance over time may determine subsequent degrees of risk for dementia and other syndromes of aging. Methods: One hundred four cognitively intact men and women followed longitudinally for up to 13 years underwent at least three MRIs with corresponding annual cognitive and neurologic assessments. Brain volume, ventricular CSF (vCSF), and total periventricular (PV) and subcortical WMH volumes were measured. Progression of MRI volumes was examined in relation to rates of cognitive, motor, and cerebral volume change based on slopes of outcomes. Results: Higher initial total and PV WMH volume was associated with total WMH, PV WMH, and vCSF progression, and with increased time and number of steps to walk 30 feet. Progression of PV WMH volume was associated with increased time to walk 30 feet. Progression of subcortical WMH volume was associated with decreased performance on logical memory testing and increased rate of vCSF volume change. Conclusion: Increased total and periventricular (PV) white matter hyperintensity (WMH) burden and progression of PV WMH burden are associated with decreased gait performance over time, while progression of subcortical WMH volume is associated with memory decline in cognitively intact elderly. Greater progression of WMH burden is associated with an increased risk of memory and gait dysfunction, and thus should not be considered a benign process.

Brain volume preserved in healthy elderly through the eleventh decade

Objective: To determine which brain regions lose volume with aging over time in healthy, nondemented elderly. Background: Cross-sectional studies suggest widespread loss of brain volume with aging. These studies may be biased by significant numbers of preclinically demented elderly in the oldest comparison groups. Longitudinal studies may allow closer determination of the effect of aging unaffected by dementia. Methods: Quantitative volumetric MRI was performed annually on 46 healthy subjects older than age 65 who had maintained cognitive health a mean of 5 years. Comparisons (analysis of variance) were made of rates of volume loss (slopes) divided into 11 young-old (mean age, 70 years), 15 middle-old (mean age, 81 years), and 20 oldest-old (mean age, 87 years) subjects. Regions of interest included CSF spaces, lobar regions, and limbic-subcortical regions. Results: There were significant differences between groups in intracranial, total brain, left hemisphere, right hemisphere, temporal lobe, basilar-subcortical region, and hippocampus volumes, with oldest-old subjects showing the smallest volumes, followed by middle-old and young-old subjects. Oldest-old subjects had significantly greater subarachnoid volumes than the younger groups. There were no significant differences in rates of change of regions of interest across age groups. Conclusions: After age 65 there is minimal brain volume loss observed over time in healthy elderly. Brain volume differences seen cross-sectionally, at any age, likely reflect small, constant rates of volume loss with healthy aging. Healthy oldest-old subjects do not show greater rates of brain loss compared with younger elderly, suggesting that large changes seen in cross-sectional studies reflect the presence of preclinical dementia in older groups.

Nutrient Biomarker Patterns, Cognitive Function, and Mri Measures of Brain Aging

Objective: To examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders. Methods: Thirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n = 104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed the relationship of these with cognitive and MRI outcomes. Results: Mean age was 87 ± 10 years and 62% of subjects were female. Two NBPs associated with more favorable cognitive and MRI measures: one high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E, and another high in plasma marine ω-3 fatty acids. A third pattern characterized by high trans fat was associated with less favorable cognitive function and less total cerebral brain volume. Depression attenuated the relationship between the marine ω-3 pattern and white matter hyperintensity volume. Conclusion: Distinct nutrient biomarker patterns detected in plasma are interpretable and account for a significant degree of variance in both cognitive function and brain volume. Objective and multivariate approaches to the study of nutrition in brain health warrant further study. These findings should be confirmed in a separate population. Neurology® 2012;78:241–249

Neurologic function in the optimally healthy oldest old: Neuropsychological evaluation

We examined cognition on a wide range of standardized neuropsychological tests in two groups of optimally healthy, elderly volunteers. One was composed of community-dwelling, functionally independent individuals aged 84 years and older, and the other group was nearly 20 years younger. The effect of aging was greatest on visual perceptual and constructional tasks rather than on memory tasks. Many cognitive functions were relatively well preserved in the optimally healthy oldest old.