Serum anticholinergic activity, white matter hyperintensities, and cognitive performance.

The authors investigated whether the cognitive impairments associated with white matter hyperintensities (WMH) in normal elderly subjects are exacerbated by any anticholinergic medications being taken by the subjects. Results showed serum anticholinergic activity (SAA) and WMH volume to have a synergistic interaction such that the cognitive decrements associated with increasing WMH volume were greatest in those older individuals in the highest quartile of the SAA distribution.

Alcohol consumption and cognitive function in late life: a longitudinal community study.

OBJECTIVE: To examine the association between alcohol use and cognitive decline in a longitudinal study of a representative elderly community sample free of dementia at baseline. METHODS: Cognitive functions and self-reported drinking habits were assessed at 2-year intervals over an average of 7 years of follow-up. Cognitive measures, grouped into composites, were examined in association with alcohol consumption. Trajectory analyses identified latent homogeneous groups with respect to alcohol use frequency over time, and their association with average decline over the same period in each cognitive domain. Models controlled for age, sex, education, depression, smoking, general mental status (Mini-Mental State Examination [MMSE]), performance on the given test at baseline, and subsequent new-onset dementia during follow-up. RESULTS: The authors found three homogeneous trajectories that they characterized as no drinking, minimal drinking, and moderate drinking. Few heavy drinkers were identified in this elderly cohort. Compared to no drinking, both minimal and moderate drinking were associated with lesser decline on the MMSE and Trailmaking tests. Minimal drinking was also associated with lesser decline on tests of learning and naming. These associations were more pronounced when comparing current drinkers to former drinkers (quitters) than to lifelong abstainers. CONCLUSION: In a representative elderly cohort over an average of 7 years, a pattern of mild-to-moderate drinking, compared to not drinking, was associated with lesser average decline in cognitive domains over the same period.

Cognitive correlates of human brain aging: a quantitative magnetic resonance imaging investigation.

The relations between age-related changes in brain structure and neuropsychological test performance in 320 elderly nonclinical volunteers (ages 66-90) were examined by using quantitative MRI data and measures of attention, information processing speed, language, memory, and visuospatial ability. Final path analyses revealed significant brain-behavior relationships for two of the six cognitive measures: the Trail Making Test part B and visual delayed memory. Poorer performance on Trails B was associated with smaller cerebral hemisphere volumes and larger volumes of peripheral CSF, lateral ventricles, and third ventricle. Poorer recall on visual delayed memory was associated with larger volumes of the lateral ventricles and third ventricle. The findings demonstrate a relationship between age-related changes in brain structure and an age-related decline in attention, psychomotor speed, and visual delayed memory. The neurobiological basis for this relationship requires further investigation.

Speed and capacity of language processing test: normative data from an older American community-dwelling sample.

This study presents normative data for the Speed and Capacity of Language Processing (SCOLP) testfrom an older American sample. The SCOLP comprises 2 subtests: Spot-the-Word, a lexical decision task, providing an estimate of premorbid intelligence, and Speed of Comprehension, providing a measure of information processing speed. Slowed performance may resultfrom normal aging, brain damage (e.g., head injury), or dementing disorders or may represent the intact performance of someone who always performed at the low end of normal. The SCOLP enables the clinician to differentiate between these possibilities. Adequate age-appropriate norms to differentiate dementia from normal aging do not exist. We present data from 424 older community-dwelling Americans (75-94 years old). The results confirm that information processing speed slows with increasing age. By contrast, increasing age has little effect on lexical decision. Thus, our data suggest that the SCOLP shows promise as a tool to help distinguish between normal aging and the early stages of dementia.

Relation of education to brain size in normal aging: implications for the reserve hypothesis.

OBJECTIVE: To examine the relations between education and age-related changes in brain structure in a nonclinical sample of elderly adults. BACKGROUND: Education may protect against cognitive decline in late life--an observation that has led to the "reserve" hypothesis of brain aging. Little is known, however, about the effect of education on age-related changes in brain structure. METHODS: Quantitative MRI of the brain was performed in 320 elderly volunteers (age range, 66 to 90 years) living independently in the community (Mini-Mental State Examination scores > or =24), all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images using computer-assisted edge detection and trace methodology. High measurement reliabilities were obtained. RESULTS: Regression analyses (adjusting for the effects of intracranial size, sex, age, age-by-sex interactions, and potential confounders) revealed significant main effects of education on peripheral (sulcal) CSF volume-a marker of cortical atrophy. Each year of education was associated with an increase in peripheral CSF volume of 1.77 mL (p<0.03). As reported previously, main effects of age (but not education) were observed for all of the remaining brain regions examined, including cerebral hemisphere volume, frontal region area, temporoparietal region area, parieto-occipital region area, lateral (Sylvian) fissure volume, lateral ventricular volume, and third ventricle volume. CONCLUSIONS: The authors' findings demonstrate a relation between education and age-related cortical atrophy in a nonclinical sample of elderly persons, and are consistent with the reserve hypothesis as well as with a small number of brain imaging studies in patients with dementia. The neurobiological basis and functional correlates of this education effect require additional investigation.

Recombination between subtypes creates a mosaic lineage of LINE-1 that is expressed and actively retrotransposing in the mouse genome.

LINE-1, or L1, elements are retrotransposons that have amplified to high-copy number during the evolution of mammals. L1 appears to amplify in waves, spawning large numbers of progeny such that elements with distinct sequence features dominate the dispersal process in a given window of time. This process generates discrete subfamilies of L1 within mammalian genomes, with the oldest being remnants, or fossils, of earlier waves of amplification. In mice, at least three distinct subfamilies of L1 were distinguished by their unique 5' ends, A, F and V. These subfamilies amplified at distinct times in the evolution of mice, with A being the youngest and V the oldest; both V and F subfamilies were believed extinct. Recent data established that a variant of the F family, TF, is actively retrotransposing. We demonstrate here that members of the TF subfamily are abundantly expressed in mouse cells and encode the major protein constituent of L1 ribonucleoprotein particles. Although members of the TF subfamily are not as numerous in the genomes of laboratory mice as are members of the older A and F subfamilies, they appear to have been activated some time ago during mouse evolution, in the common ancestor of Mus spretus and Mus domesticus. Phylogenetic analysis demonstrates that this modern, active form of TF-type L1 has a composite evolutionary history, showing evidence of multiple recombinations between distinct L1 variants, including members of the A and F subfamilies.

Sex differences in brain aging: a quantitative magnetic resonance imaging study.

BACKGROUND: Little is known about the effect of sex on age-related changes in brain structure. METHODS: Quantitative magnetic resonance imaging of the brain was performed in 330 elderly (age range, 66-96 years) volunteers living independently in the community, all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images by means of computer-assisted edge detection and trace methods. High measurement reliabilities were obtained. RESULTS: Age-specific changes in brain size were significantly greater in men than women for the peripheral (sulcal) cerebrospinal fluid volume, the lateral (sylvian) fissure cerebrospinal fluid volume, and the parieto-occipital region area. Main effects of age were observed for all the remaining brain regions examined (cerebral hemisphere volume, frontal region area, temporoparietal region area, lateral ventricular volume, and third ventricle volume), but these effects were similar in men and women. Asymmetries in brain structures were not affected by aging in either sex. CONCLUSIONS: Our results are generally consistent with the few published studies on sex differences in brain aging and suggest that, for at least some structures, aging effects may be more apparent in men than women. The neurobiological bases and functional correlates of these sex differences require further investigation.