Pamela M. Greenwood

The frontal aging hypothesis evaluated.

That the human frontal lobes are particularly vulnerable to age-related deterioration has been frequently invoked as an explanation of functional decline in aging. This frontal aging hypothesis is evaluated in this review by examining evidence of selectively reduced frontal lobe function in aging. The frontal aging hypothesis predicts that functions largely dependent on frontal regions would decline in aging, while functions largely independent of frontal lobes would remain relatively spared. The hypothesis further predicts that age-related brain change would selectively impact frontal regions. The literatures on working memory, visuospatial attention, face recognition, and implicit memory were reviewed as exemplars of functions dependent on prefrontal, parietal, temporal and occipitotemporal cortices, respectively, with a view to establishing mediating structures and effects of aging. Age sensitivity was seen both in functions dependent on frontal integrity as well as in functions apparently independent of frontal integrity. Further, although prefrontal areas exhibit age-related decreases in regional volume, blood flow and metabolism, nonfrontal cortical regions undergo similar declines. It is concluded that while the frontal lobes are subject to age-related changes reflected in both behavior and pathology, there is only weak and conflicting evidence that frontal regions are selectively and differentially affected by aging. It is argued that a network-based theory of cognitive aging has advantages over the localizationist approach inherent in the frontal aging hypothesis.

Effects of apolipoprotein E genotype on spatial attention, working memory, and their interaction in healthy, middle-aged adults: results From the National Institute of Mental Health's BIOCARD study.

The cognitive consequences of the apolipoprotein E-epsilon4 (APOE-epsilon4) allele were examined in middle age, before likely onset of symptoms of Alzheimers disease. The authors identified 3 cognitive processes--visuospatial attention, spatial working memory, and the effect of visuospatial attention on working memory--and devised behavioral assays of the integrity of components of these processes. Redirecting visuospatial attention, retention of memory for location, and attentional modulation of memory of target location were affected by APOE genotype. Visuospatial attention showed additive effects of epsilon4 gene dose; each additional epsilon4 allele inherited further slowed disengagement from invalidly cued space. In contrast, working memory performance was affected only in epsilon4 homozygotes. Effect sizes for the APOE gene were moderate to large, ranging from 14% to 24%. Effects of APOE genotype on component processes of cognition in healthy, middle-aged adults is consistent with the emergence in adulthood of an APOE-epsilon4 cognitive phenotype.

Changes in visuospatial attention over the adult lifespan

Shifts of visual attention elicited by spatial cues were examined for detection and letter-discrimination tasks in 90 normal adults ranging in age over each decade from the 20s to the 70s. Spatial cues were valid, invalid, or neutral in indicating probable target location and were presented either centrally at fixation or peripherally 6.7 degrees to the left or right of fixation. Stimulus-onset asynchrony (SOA) between cue and target was varied between 200, 500 and 2000 msec. Reaction time (RT) costs and benefits associated with spatial cueing did not vary with age for: (1) the detection task; (2) the letter-discrimination task with peripheral cues; and (3) the letter-discrimination task with central cues at a short (200 msec) SOA. RT costs and benefits increased with age only for SOAs greater than 200 msec with central cueing in the discrimination task. In general, the efficiency of cue-based shifts of visuospatial attention appears relatively resistant to the effects of adult age up to 79 years. When an age effect was found, RT costs and benefits increased steadily across all age decades, the correlation with age being 0.25 and 0.38 for the 500 and 2000 msec SOAs, respectively. The findings suggest a qualitative difference in the influence of normal adult aging and effects of dementia noted in previous studies; normal aging has only a weak influence on voluntary attention shifts, whereas dementia affects both voluntary and involuntary modes of attention shifting.

The Apolipoprotein E Gene, Attention, and Brain Function

The epsilon4 allele of the apolipoprotein E (ApoE) gene is associated with alterations in brain function and is a risk factor for Alzheimers disease (AD). Changes in components of visuospatial attention with ApoE-epsilon4, aging, and AD are described. Healthy middle-aged adults without dementia who have the ApoE-epsilon4 gene show deficits in spatial attention and working memory that are qualitatively similar to those seen in clinically diagnosed AD patients. The findings support an association between ApoE polymorphism and specific components of visuospatial attention. Molecular mechanisms that may mediate the ApoE-attention link by modulating cholinergic neurotransmission to the posterior parietal cortex are discussed. Studies of attention and brain function in ApoE-epsilon4 carriers without dementia can advance knowledge of the genetics of visual attention, may enhance understanding of the preclinical phase of AD, and may lead to better methods for early AD detection.

Normal genetic variation, cognition, and aging.

This article reviews the modulation of cognitive function by normal genetic variation. Although the heritability of g is well established, the genes that modulate specific cognitive functions are largely unidentified. Application of the allelic association approach to individual differences in cognition has begun to reveal the effects of single nucleotide polymorphisms on specific and general cognitive functions. This article proposes a framework for relating genotype to cognitive phenotype by considering the effect of genetic variation on the protein product of specific genes within the context of the neural basis of particular cognitive domains. Specificity of effects is considered, from genes controlling part of one receptor type to genes controlling agents of neuronal repair, and evidence is reviewed of cognitive modulation by polymorphisms in dopaminergic and cholinergic receptor genes, dopaminergic enzyme genes, and neurotrophic genes. Although allelic variation in certain genes can be reliably linked to cognition--specifically to components of attention, working memory, and executive function in healthy adults--the specificity, generality, and replicability of the effects are not fully known.

Controlling the focus of spatial attention during visual search: Effects of advanced aging and Alzheimer disease.

It was hypothesized that slowed visual search in healthy adult aging arises from reduced ability to adjust the size of the attentional focus. A novel, cued-visual search task manipulated the scale of spatial attention in a complex field in healthy elderly individuals and patients with dementia of the Alzheimer type (DAT). Precues indicated with varying validity the size and location of the area to be searched. Location precues exerted the strongest effects on conjunction search and the weakest effects on feature search. As the size of valid location cues decreased, conjunction search was facilitated. These effects declined progressively with advanced age and the onset of DAT. As the size of invalid cues increased, conjunction search was first facilitated, then slowed, but neither age nor DAT altered this effect. These results indicate that both Alzheimers disease and, to a lesser degree, advanced aging, reduce control of the spatial focus of attention.

Scale of attentional focus in visual search.

The effects of the spatial scale of attention on feature and conjunction search were examined in two experiments. Adult participants in three age groups—young, young-old, and old-old—were given precues of varying validity and precision in indicating the location of a target letter subsequently presented in a visual array. Systematic decreases in the size of a valid precue (toward the size of the target) progressively facilitated both feature and conjunction search, with a greater benefit accruing to conjunction search. Age-related slowing in conjunction search was mitigated by precise (small and valid) precues, presumably because they reduced the need for participants in the young-old group to focus and to shift attention. Nevertheless, this benefit was reduced in the old-old group. The effects of valid location precue size varied with cue-target stimulus onset asynchrony (SOA) in a manner that interacted with search difficulty: Effects of cue size developed more rapidly in feature search but more slowly in conjunction search. Finally, when precues were invalid for target location, search was faster with larger sized precues. Thus, in both easy feature search and hard conjunction search, the scale of visuospatial attention modulates the speed of visual search. Furthermore, when the SOA is sufficiently long for cue effects to develop, the ability to dynamically adjust the scale of visuospatial attention appears to decline in advanced age. These results go beyond current models in suggesting that visuospatial attention possesses two dynamic properties—shifting in space and varying in scale—that are deployed independently, depending on task demands.

Sustained-attention capacity in young and older adults.

The sustained-attention capacity of young (21-29 years) and older (65-78 years) adults was examined using a high-event rate digit-discrimination vigilance task presented at three levels of stimulus degradation. Increased stimulus degradation led to a reduction in the hit rate and to a greater decline in hit rate over blocks (increased vigilance decrement). Sensitivity (d) declined over blocks only at the highest level of stimulus degradation. Older adults had a lower hit rate and showed greater vigilance decrement than young adults, particularly when stimuli were highly degraded. However, both age groups showed the same pattern of stability in sensitivity when stimulus degradation was moderate, and sensitivity decrement over time when stimulus degradation was high. The results suggest that the process of sustained allocation of capacity--as reflected in temporal changes in sensitivity--operates similarly in young and older adults.

Specificity of the Effect of a Nicotinic Receptor Polymorphism on Individual Differences in Visuospatial Attention

Cortical neurotransmitter availability is known to exert domain-specific effects on cognitive performance. Hence, normal variation in genes with a role in neurotransmission may also have specific effects on cognition. We tested this hypothesis by examining associations between polymorphisms in genes affecting cholinergic and noradrenergic neurotransmission and individual differences in visuospatial attention. Healthy individuals were administered a cued visual search task which varied the size of precues to the location of a target letter embedded in a 15-letter array. Cues encompassed 1, 3, 9, or 15 letters. Search speed increased linearly with precue size, indicative of a spatial attentional scaling mechanism. The strength of attentional scaling increased progressively with the number of C alleles (0, 1, or 2) of the alpha-4 nicotinic receptor gene C1545T polymorphism (n = 104). No association was found for the dopamine beta hydroxylase gene G444A polymorphism (n = 135). These findings point to the specificity of genetic neuromodulation. Whereas variation in a gene linked to cholinergic transmission systematically modulated the ability to scale the focus of visuospatial attention, variation in a gene governing dopamine availability did not. The results show that normal variation in a gene controlling a nicotinic receptor makes a selective contribution to individual differences in visuospatial attention.

Alzheimer disease constricts the dynamic range of spatial attention in visual search.

A cued visual search task was used to examine the dynamic range over which spatial attention affects target identification during visual search. Precues varied in validity (valid, invalid, or neutral) and in precision (cue size) of target localization. Participants were young-old (65-74 years) and old-old (75-85 years) elderly adults and individuals in the mild stage of dementia of the Alzheimer type (DAT). For all participants, search was speeded as the precision with which a precue surrounding the location of a subsequently appearing target increased (precue size decreased). The cue size effect was evident in both feature and conjunction search, but was greatly reduced in both old-old and DAT groups compared to the young-old. However, whereas all non-demented adults showed a progressive modulation of search efficiency over the entire range of cue sizes, the dynamic range of spatial attention was restricted to the most precise cue in the DAT group. The restriction in the dynamic range of spatial attention may represent an underlying component of the impairment in perceptual and memory functioning found in early-stage DAT.