Debra A. Fleischman

White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study.

Diffusion tensor imaging (DTI) can detect, in vivo, the directionality of molecular diffusion and estimate the microstructural integrity of white matter (WM) tracts. In this study, we examined WM changes in patients with Alzheimers disease (AD) and in subjects with amnestic mild cognitive impairment (MCI) who are at greater risk for developing AD. A DTI index of WM integrity, fractional anisotropy (FA), was calculated in 14 patients with probable mild AD, 14 participants with MCI and 21 elderly healthy controls (NC). Voxel-by-voxel comparisons showed significant regional reductions of FA in participants with MCI and AD compared to controls in multiple posterior white matter regions. Moreover, there was substantial overlap of locations of regional decrease in FA in the MCI and AD groups. These data demonstrate that white matter changes occur in MCI, prior to the development of dementia.

Double Dissociation Between Memory Systems Underlying Explicit and Implicit Memory in the Human Brain

Amnesic patients have impaired explicit memory that is evident in poor recall and recognition of words, yet can have intact implicit memory for words as measured by repetition priming, the enhanced efficiency for reprocessing those words The dissociation between explicit and implicit memory for words is a fundamental characteristic of normal cognition that could reflect two different functional architectures of the human brain two separate processing systems or two levels of operation of a single system with implicit memory less demanding of that system We present a patient who has a lesion in the right occipital lobe and who showed intact explicit and impaired implicit memory for words The deficit was specific to visual priming The double dissociation between explicit and implicit visual memory for words indicates that separate processing systems mediate these two forms of memory, and that a memory system in right occipital cortex mediates implicit visual memory for words

Repetition priming in normal aging and Alzheimer's disease: A review of findings and theories.

On repetition priming tasks, memory is measured indirectly as a change in performance due to recent experience. It is often functionally and neurally dissociated from performance on explicit memory tasks, which directly measure conscious recall or recognition of recent events. Repetition priming has therefore been extensively studied in normal aging and Alzheimers disease, which feature mild to severe changes in explicit memory. Initial studies indicated that repetition priming was immune to the effects of aging and greatly reduced in Alzheimers disease (AD). As more studies have been performed, however, these initial conclusions appear less clear than before and, in the case of AD, actually misleading. The purpose of this article is to provide a comprehensive review of this rapidly expanding literature, articulate the issues that are critical to interpreting the empirical results, and discuss what new conclusions are suggested by the overall pattern of findings.

Common variants at 12q14 and 12q24 are associated with hippocampal volume

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimers disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10−7. In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10−11) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10−11). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10−7) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10−7); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.

MRI predictors of risk of incident Alzheimer disease: A longitudinal study

Objective: To determine if baseline entorhinal and hippocampal volumes and their rate of atrophy could predict the risk of incident Alzheimer disease (AD). Methods: The authors used proportional odds models to assess the relationship between entorhinal and hippocampal size and risk of incident AD among 58 nondemented elderly people. All participants were followed with annual clinical evaluations and structural MRI scans for up to 5 years (baseline and 5 years of follow-up). At baseline, 23 of 58 participants received a diagnosis of amnestic mild cognitive impairment (MCI) and 35 of 58 were healthy control subjects with no cognitive impairment. Structural MRI scans were acquired with a T1-weighted three-dimensional spoiled gradient-recalled echo pulse sequence in a 1.5 T scanner. Entorhinal and hippocampal volumes were derived from 1.6-mm gapless coronal images reformatted to be perpendicular to the long axis of the hippocampus and were normalized by dividing with intracranial volume. Results: Fourteen of 58 nondemented participants developed AD during the follow-up period. Initial diagnosis of MCI was a significant predictor of incident AD. In addition, both baseline entorhinal volume and its slope of decline were independent predictors of incident AD, but initial hippocampal size and its rate of decline were not, after controlling for entorhinal volume. Conclusion: In nondemented individuals, entorhinal cortex atrophy is associated with risk of Alzheimer disease.

Association between Late-Life Social Activity and Motor Decline in Older Adults

BACKGROUND Loss of motor function is a common consequence of aging, but little is known about the factors that predict idiopathic motor decline. Our objective was to test the hypothesis that late-life social activity is related to the rate of change in motor function in old age. METHODS Longitudinal cohort study with a mean follow-up of 4.9 years with 906 persons without stroke, Parkinson disease, or dementia participating in the Rush Memory and Aging Project. At baseline, participants rated the frequency of their current participation in common social activities from which a summary measure of social activity was derived. The main outcome measure was annual change in a composite measure of global motor function, based on 9 measures of muscle strength and 9 motor performances. RESULTS Mean (SD) social activity score at baseline was 2.6 (0.58), with higher scores indicating more frequent participation in social activities. In a generalized estimating equation model, controlling for age, sex, and education, global motor function declined by approximately 0.05 U/y (estimate, 0.016; 95% confidence interval [CI], -0.057 to 0.041 [P = .02]). Each 1-point decrease in social activity was associated with approximately a 33% more rapid rate of decline in motor function (estimate, 0.016; 95% CI, 0.003 to 0.029 [P = .02]). The effect of each 1-point decrease in the social activity score at baseline on the rate of change in global motor function was the same as being approximately 5 years older at baseline (age estimate, -0.003; 95% CI, -0.004 to -0.002 [P<.001]). Furthermore, this amount of motor decline per year was associated with a more than 40% increased risk of death (hazard ratio, 1.44; 95% CI, 1.30 to 1.60) and a 65% increased risk of incident Katz disability (hazard ratio, 1.65; 95% CI, 1.48 to 1.83). The association of social activity with the rate of global motor decline did not vary along demographic lines and was unchanged (estimate, 0.025; 95% CI, 0.005 to 0.045 [P = .01]) after controlling for potential confounders including late-life physical and cognitive activity, disability, global cognition depressive symptoms, body composition, and chronic medical conditions. CONCLUSION Less frequent participation in social activities is associated with a more rapid rate of motor function decline in old age.

Convergent behavioral and neuropsychological evidence for a distinction between identification and production forms of repetition priming

Four experiments examined a distinction between kinds of repetition priming which involve either the identification of the form or meaning of a stimulus or the production of a response on the basis of a cue. Patients with Alzheimers disease had intact priming on picture-naming and category-exemplar identification tasks and impaired priming on word-stem completion and category-exemplar production tasks. Division of study-phase attention in healthy participants reduced priming on word-stem completion and category-exemplar production tasks but not on picture-naming and category-exemplar identification tasks. The parallel dissociations in normal and abnormal memory cannot be explained by implicit-explicit or perceptual-conceptual distinctions but are explained by an identification-production distinction. There may be separable cognitive and neural bases for implicit modulation of identification and production forms of knowledge.

A longitudinal study of implicit and explicit memory in old persons.

Decline in explicit memory with advancing age is a common finding, but it is unclear whether implicit memory (repetition priming) declines or remains stable. Meta-analyses of studies that examined differences between extreme groups (young-old), typically at a single point in time and on a single test, suggest that a mild reduction in priming occurs with advancing age. The authors examined explicit memory and priming, on multiple tests over 4 annual data-collection waves, in a large group of older persons without dementia at baseline. Explicit memory declined significantly, but priming remained stable. Findings indicate that explicit memory and priming are dissociable on the basis of age-related change and that mildly reduced priming is not an inevitable consequence of growing older.

Repetition priming in aging and Alzheimer's disease: an integrative review and future directions.

Two decades of research examining repetition priming in aging and Alzheimers disease (AD) has yielded a large body of contradictory findings due to differences between studies in participant and task characteristics. Recent research that has employed methodological advances indicates that this form of implicit memory is preserved in healthy aging. When a priming deficit does occur in studies of aging, it is likely a very early signal of neurological disease. Future directions for research in this area include linking priming ability to known risk factors for development of AD, integrating priming measures into clinical neuropsychological assessment batteries, and implementing programs of cognitive retraining that enhance memory using stimulus repetition techniques.

Physical Activity and Leg Strength Predict Decline in Mobility Performance in Older Persons

OBJECTIVES: To assess the extent to which physical activity and leg strength are associated with change in mobility in older persons.