Neurologic evaluation of the optimally healthy oldest old.

OBJECTIVE: Individuals aged 85 years or older (the "oldest old") are the fastest-growing age group in the United States. Because there is little information characterizing expected neurologic function in this group, our goal was to determine clinical neurologic traits characteristic of the optimally healthy oldest old. DESIGN: Standardized neurologic evaluation findings of optimally healthy persons older than 84 years compared with those of equally healthy control subjects aged 65 to 74 years. SETTING: Community-based, longitudinal aging study. PARTICIPANTS: Community-residing, consecutively recruited volunteers who were screened for the absence of chronic disease or medication use. MAIN OUTCOME MEASURE: Standardized neurologic examination coded into ordinal or interval variables. RESULTS: Significant between-group differences were greatest for tests of mental status, sensory function (ie, smell, hearing, vibratory discrimination, and stereognosis), oculomotor function, distal movement speed, and balance. Discriminant function analysis suggests that of these changes, membership in the oldest group is best predicted by poor performance on clinical tests of balance (heel-toe walking and one-leg balancing with eyes closed), smell, and visual pursuit. CONCLUSIONS: Many neurologic signs appear with aging that cannot be attributed to disease, even in the very old. Deficits in balance, olfaction, and visual pursuit discriminate best between the aging changes of the healthy very old and changes seen in younger elderly persons.

Attention deficit in Alzheimer's disease is not simulated by an anticholinergic/antihistaminergic drug and is distinct from deficits in healthy aging.

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.

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.

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.

Cognitive markers preceding Alzheimer's dementia in the healthy oldest old.

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.

Age-related brain changes associated with motor function in healthy older people.

OBJECTIVE: To identify the MRI imaging findings associated with motor changes in healthy older people. DESIGN: A cross-sectional study. SETTING: A study of neurologic function in very healthy older people, the Oregon Brain Aging Study. PARTICIPANTS: Clinical and MRI data were examined in 50 very healthy older subjects (mean age = 85.1, SD = 7.2 years). MEASUREMENTS: Clinical measures (finger tapping, hand opening and closing, steps and time to walk 30 feet and timed standing on one foot) were dependent variables in multiple regression analyses using age and the following MRI measures as independent variables: total brain volume (TBV)/intracranial volume; ventricular volume/TBV; periventricular high signal/TBV; deep high signal/TBV. RESULTS: The number of steps and the time to walk 30 feet were each associated with periventricular high signal (steps: r = .58, P < .001; time: r = .60, P < .001) and ventricular volume (steps: r = .54, P < .001; time: r = .58, P < .001). These associations remained significant after adjusting for age. None of the other clinical variables was associated with the MRI volumes. CONCLUSIONS: Gait measures were associated significantly with periventricular high signal and ventricular volume. These CNS changes contribute to the cause of these important markers of aging.

Memory testing in dementia: how much is enough?

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.

Longitudinal analysis of the effects of the aging process on neuropsychological test performance in the healthy young-old and oldest-old.

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.

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.

Natural history of cognitive decline in the old old.

OBJECTIVE: To prospectively examine the occurrence and outcome of cognitive decline in healthy, community-dwelling elders. METHODS: Ninety-five elders (mean age 84 years) who at entry had no cognitive impairment were followed for up to 13 years. Cognitive decline was defined as obtaining either a Clinical Dementia Rating (CDR) = 0.5 or Mini-Mental State Examination (MMSE) score < 24 on two examinations. RESULTS: Three outcomes of aging were determined: intact cognition, persistent cognitive decline without progression to dementia, and dementia. Whereas 49% remained cognitively intact, 51% developed cognitive decline. Mean follow-up to first CDR 0.5 was 3.8 years and age at conversion was 90.0 years. Those who remained cognitively intact had better memory at entry and were less likely to have APOE4 than those who developed cognitive decline. Of the 48 participants with cognitive decline, 27 (56%) developed dementia (CDR > or =1) a mean of 2.8 years later. Participants with cognitive decline who progressed to dementia had poorer confrontation naming at the time of their first CDR 0.5 than those with persistent cognitive decline who did not progress during follow-up. CONCLUSION: The old old are at high risk for developing cognitive decline but many will not progress to dementia in the next 2 to 3 years or even beyond. These findings are important for understanding the prognosis of cognitive decline and for the design of treatment trials for AD. APOE genotype is a risk factor for cognitive decline.