Normative data for healthy older adults and an abbreviated version of the Stroop test.

Normative data for the Kaplan version of the Stroop Test are presented for 153 healthy, cognitively intact older adults aged 50-89 years. Increasing age was associated with decreased performance on all three subtests (Stroop A, Stroop B, and Stroop C), while years of education was only associated with Stroop B performance. Hence the normative data were stratified by age into three groups (50-64, 65-74, 75-89). Completion times for the first half of each trial (half-time scores) were found to have good split-half reliability and correlated highly with the original full administration scores. Means and standard deviations for the half-time administration are also presented for this sample. The current study provides more comprehensive normative data for older adults than previously available, as well as normative information for half-time scores that may have future clinical utility as an alternative, abbreviated version of the Kaplan Stroop Test.

Age-related slowing in cognitive processing speed is associated with myelin integrity in a very healthy elderly sample.

Performance on measures of cognitive processing speed (CPS) slows with age, but the biological basis associated with this cognitive phenomenon remains incompletely understood. We assessed the hypothesis that the age-related slowing in CPS is associated with myelin breakdown in late-myelinating regions in a very healthy elderly population. An in vivo magnetic resonance imaging (MRI) biomarker of myelin integrity was obtained from the prefrontal lobe white matter and the genu of the corpus callosum for 152 healthy elderly adults. These regions myelinate later in brain development and are more vulnerable to breakdown due to the effects of normal aging. To evaluate regional specificity, we also assessed the splenium of the corpus callosum as a comparison region, which myelinates early in development and primarily contains axons involved in visual processing. The measure of myelin integrity was significantly correlated with CPS in highly vulnerable late-myelinating regions but not in the splenium. These results have implications for the neurobiology of the cognitive changes associated with brain aging.

Gender and iron genes may modify associations between brain iron and memory in healthy aging.

Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders that impact memory including Alzheimer's disease (AD). Higher brain iron levels are associated with male gender and presence of highly prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2)). In this study, we examined whether in healthy older individuals memory performance is associated with increased brain iron, and whether gender and gene variant carrier (IRON+) vs noncarrier (IRON-) status (for HFE H63D/TfC2) modify the associations. Tissue iron deposited in ferritin molecules can be measured in vivo with magnetic resonance imaging utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in hippocampus, basal ganglia, and white matter, and IRON+ vs IRON- status was determined in a cohort of 63 healthy older individuals. Three cognitive domains were assessed: verbal memory (delayed recall), working memory/attention, and processing speed. Independent of gene status, worse verbal-memory performance was associated with higher hippocampal iron in men (r=-0.50, p=0.003) but not in women. Independent of gender, worse verbal working memory performance was associated with higher basal ganglia iron in IRON- group (r=-0.49, p=0.005) but not in the IRON+ group. Between-group interactions (p=0.006) were noted for both of these associations. No significant associations with white matter or processing speed were observed. The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups.

Lifespan trajectory of myelin integrity and maximum motor speed.

OBJECTIVE: Myelination of the human brain results in roughly quadratic trajectories of myelin content and integrity, reaching a maximum in mid-life and then declining in older age. This trajectory is most evident in vulnerable later myelinating association regions such as frontal lobes and may be the biological substrate for similar trajectories of cognitive processing speed. Speed of movement, such as maximal finger tapping speed (FTS), requires high-frequency action potential (AP) bursts and is associated with myelin integrity. We tested the hypothesis that the age-related trajectory of FTS is related to brain myelin integrity. METHODS: A sensitive in vivo MRI biomarker of myelin integrity (calculated transverse relaxation rates (R(2))) of frontal lobe white matter (FLwm) was measured in a sample of very healthy males (N=72) between 23 and 80 years of age. To assess specificity, R(2) of a contrasting early-myelinating region (splenium of the corpus callosum) was also measured. RESULTS: FLwm R(2) and FTS measures were significantly correlated (r=.45, p<.0001) with no association noted in the early-myelinating region (splenium). Both FLwm R(2) and FTS had significantly quadratic lifespan trajectories that were virtually indistinguishable and both reached a peak at 39 years of age and declined with an accelerating trajectory thereafter. CONCLUSIONS: The results suggest that in this very healthy male sample, maximum motor speed requiring high-frequency AP burst may depend on brain myelin integrity. To the extent that the FLwm changes assessed by R(2) contribute to an age-related reduction in AP burst frequency, it is possible that other brain functions dependent on AP bursts may also be affected. Non-invasive measures of myelin integrity together with testing of basic measures of processing speed may aid in developing and targeting anti-aging treatments to mitigate age-related functional declines.

Persistence of neuropsychological testing deficits in mild cognitive impairment.

BACKGROUND: The significant variability across studies of mild cognitive impairment (MCI) in rates of progression to Alzheimer's disease (AD) and reversion to normal cognition may be due to differences in specific neuropsychological tests and thresholds used to define MCI. METHODS: We assessed 115 subjects with amnestic (AMN) or non-amnestic (NON) MCI on a standardized neuropsychological battery at baseline and after a mean follow-up of 16.4 months to determine the prevalence and persistence of deficits identified with specific tests. RESULTS: The prevalence of impaired performance varied widely across tests. Deficits were more persistent in the AMN group than in the NON group. Baseline deficits in Visual Reproduction II and the California Verbal Learning Test were the best predictors of persistent memory impairment. Subjects who at baseline were impaired on multiple memory tests or had poorer overall memory performance were more likely to exhibit persistent memory deficits. CONCLUSIONS: The use of different neuropsychological tests and thresholds to diagnose MCI identified subsets of subjects with different rates of persistence of cognitive impairment. Standardization of the operational definition of cognitive impairment in MCI may result in more consistent predictions of progression to AD.

Apolipoprotein E affects both myelin breakdown and cognition: implications for age-related trajectories of decline into dementia.

BACKGROUND: Age-related myelin breakdown is most evident in later-myelinating white matter (LMwm) brain regions. This process might degrade cognitive processing speed (CPS) underlying age-related cognitive decline and the predominance of age as a risk factor for Alzheimer's disease (AD). Apolipoprotein E (ApoE) 4 allele is the second most important AD risk factor. We tested the hypothesis that ApoE4 accelerates age-related slowing in CPS through the process of myelin breakdown. METHODS: Calculated transverse relaxation rates (R(2)), an indirect magnetic resonance imaging measure of myelin breakdown in LMwm, and measures of CPS were obtained in 22 ApoE4+ and 80 ApoE4-, healthy "younger-old" individuals. To assess specificity, contrasting early-myelinating white matter region and memory task were also examined. RESULTS: The CPS versus LMwm R(2) remained significant in the ApoE4+ group even after age was statistically adjusted (r = .65, p = .001) and differed from the correlation observed in the ApoE4- group (Fisher's z test = 3.22, p < .002). No significant associations were observed with the contrast region and memory task in either ApoE subgroup. CONCLUSIONS: A specific association between CPS and myelin breakdown in LMwm exists in asymptomatic "younger-old" individuals at increased genetic risk for AD. Although inferences of change over time and causality are limited by the cross-sectional study design, this finding lends support to the hypotheses that myelin breakdown underlies age-related slowing in CPS and that by altering the trajectory of myelin breakdown, ApoE alleles shift the age at onset of cognitive decline. Combined use of biomarkers and CPS measures might be useful in developing and targeting primary prevention treatments for AD.