Visual Perceptual Organization Ability in Autopsy-Verified Dementia with Lewy Bodies and Alzheimer's Disease.

OBJECTIVES: Prominent impairment of visuospatial processing is a feature of dementia with Lewy bodies (DLB), and diagnosis of this impairment may help clinically distinguish DLB from Alzheimer's disease (AD). The current study compared autopsy-confirmed DLB and AD patients on the Hooper Visual Organization Test (VOT), a test that requires perceptual and mental reorganization of parts of an object into an identifiable whole. The VOT may be particularly sensitive to DLB since it involves integration of visual information processed in separate dorsal and ventral visual "streams". METHODS: Demographically similar DLB (n=28), AD (n=115), and normal control (NC; n=85) participants were compared on the VOT and additional neuropsychological tests. Patient groups did not differ in dementia severity at time of VOT testing. High and Low AD-Braak stage DLB subgroups were compared to examine the influence of concomitant AD pathology on VOT performance. RESULTS: Both patient groups were impaired compared to NC participants. VOT scores of DLB patients were significantly lower than those of AD patients. The diagnostic sensitivity and specificity of the VOT for patients versus controls was good, but marginal for DLB versus AD. High-Braak and low-Braak DLB patients did not differ on the VOT, but High-Braak DLB performed worse than Low-Braak DLB on tests of episodic memory and language. CONCLUSIONS: Visual perceptual organization ability is more impaired in DLB than AD but not strongly diagnostic. The disproportionate severity of this visual perceptual deficit in DLB is not related to degree of concomitant AD pathology, which suggests that it might primarily reflect Lewy body pathology. (JINS, 2016, 22, 609-619).

The effect of interference on temporal order memory in individuals with Parkinson's disease.

Memory for the temporal order of items or events in a sequence has been shown to be impaired in older adults and individuals with Parkinson's disease (PD). The present study examined the effects of high and low interference on temporal order memory in individuals diagnosed with PD (n=20) and demographically similar healthy older adults (n=20) utilizing a computerized task used in previously published studies. During the sample phase of each trial, a series of eight circles were randomly presented one at a time in eight different spatial locations. Participants were instructed to remember the sequence in which the circles appeared in the locations. During the choice phase, participants were presented with two circles in two different locations and were asked to indicate which circle appeared earliest in the sample phase sequence. The two circles were separated by one of four possible temporal separation lags (0, 2, 4, and 6), defined as the number of circles occurring in the sample phase sequence between the two choice phase circles. Shorter temporal lags (e.g., 0 and 2 lags) were hypothesized to result in higher interference compared to longer temporal lags (e.g., 4 and 6 lags). The results demonstrated that on trials involving high interference, no differences were found between the two groups. However, healthy older adults significantly outperformed individuals with PD (p<0.05) on trials involving low interference. Although differences were found between the PD and healthy older adult groups, both groups significantly improved on low interference trials compared to high interference trials (p<0.001). The findings indicate that temporal order memory improves in healthy older adults and individuals with PD when interference is reduced. However, individuals with PD demonstrated poorer temporal order memory even with less interference. Therefore, temporal order memory is differentially affected by interference in healthy older adults and individuals with PD. Given that both groups did improve with lessened interference, behavioral interventions that minimize temporal interference potentially could improve memory function in older adults and to a lesser extent in individuals with PD.

Early visuospatial deficits predict the occurrence of visual hallucinations in autopsy-confirmed dementia with Lewy bodies.

OBJECTIVES: The current study explored the value of visuospatial findings for predicting the occurrence of visual hallucinations (VH) in a sample of patients with dementia with Lewy bodies (DLB) compared with patients with Alzheimer disease (AD). PARTICIPANTS/MEASUREMENTS: Retrospective analysis of 55 autopsy-confirmed DLB and 55 demographically similar, autopsy-confirmed AD cases determined whether severe initial visuospatial deficits on the WISC-R Block Design subtest predicted the development of VH. Visuospatial deficits were considered severe if Block Design z scores were 2.5 or more standard deviations below the mean of a well-characterized normal control group (severe visuospatial deficits [severe-VIS]; DLB: n = 35, AD: n = 26) and otherwise were considered mild (mild visuospatial deficits [mild-VIS]; DLB: n = 20, AD: n = 29). RESULTS: Forty percent of the severe-VIS DLB group had baseline VH compared with 0% of mild-VIS DLB patients. Only 8% of the severe-VIS and 3% mild-VIS AD patients had baseline VH. During the follow-up period (mean = 5.0 years), an additional 61% of the severe-VIS but only 11% of the mild-VIS DLB patients developed VH. In that period, 38% of the severe-VIS and 20% of the mild-VIS AD patients developed VH. After considering initial MMSE score and rate of decline, logistic regression analyses found that performance on Block Design significantly predicted the presence of VH in the DLB group but not the AD group. CONCLUSIONS: The presence of early, severe deficits on neuropsychological tests of visuospatial skill increases the likelihood that patients with suspected DLB will develop the prototypical DLB syndrome. The presence of such deficits may identify those DLB patients whose syndrome is driven by α-synuclein pathology rather than AD pathology and may inform treatment plans as well as future research.

Perception of Fragmented Letters by Patients With Pathologically Confirmed Dementia With Lewy Bodies or Alzheimer Disease.

BACKGROUND AND OBJECTIVE: Patients with dementia with Lewy bodies perform worse than those with Alzheimer disease (AD) on tests of visual perception, but the clinical utility of these tests remains unknown because studies often had clinically diagnosed groups that may inadvertently cross-contaminate Lewy body disease (LBD) with pure AD pathology, used experimental tests not easily adaptable for clinical use, and had no way to examine relationships between the severity of LBD pathology and degree of cognitive impairment. Therefore, we sought to determine whether performance on a widely used clinical test of visuoperceptual ability effectively differentiates between patients with autopsy-confirmed LBD or AD and correlates with the severity of LBD pathology. METHODS: Patients with mild to moderate dementia (n = 42) and cognitively healthy controls (n = 22) performed a Fragmented Letters Test in which they identified letters of the alphabet that were randomly visually degraded by 70% and additional visuospatial and episodic memory tests. At autopsy, dementia cases were confirmed to have LBD (n = 19), all with concomitant AD, or only AD (n = 23). Severity of α-synuclein pathology in the hippocampus and neocortex was rated on an ordinal scale. RESULTS: Patients with LBD performed worse than those with AD (B = -2.80 ± 0.91, p = 0.009) and healthy controls (B = -3.34 ± 1.09, p = 0.01) on the Fragmented Letters Test after adjustment for age, sex, education, Mini-Mental State Examination score, and ability to name intact letters. Patients with AD did not differ from controls (B = -0.55 ± 1.08, p = 0.87). The test effectively distinguished between patients with LBD or AD with 73% sensitivity and 87% specificity, and the area under the curve in receiver operating characteristic analyses was 0.85 (95% CI 0.72-0.95), higher than for standard tests of visuospatial ability (Block Design; 0.72; CI 0.35-0.75) or memory (California Verbal Learning Test, trials 1-5; 0.55; CI 0.57-0.88). Fragmented Letters Test scores were negatively correlated with LBD pathology density ratings in hippocampus and neocortical regions (Spearman rs = -0.53 to -0.69). DISCUSSION: Fragmented Letters Test performance can effectively differentiate patients with LBD pathology from those with only AD pathology at a mild to moderate stage of dementia, even when LBD occurs with significant concomitant AD pathology, and may also be useful for gauging the severity of cortical α-synuclein pathology in those with LBD.

Motion discrimination in dementia with Lewy bodies and Alzheimer disease.

OBJECTIVE: Visual processing abilities of patients with dementia with Lewy bodies (DLB) or Alzheimer disease (AD) dementia were assessed psychophysically using a simple horizontal motion discrimination task that engages the dorsal visual processing stream. METHODS: Participants included patients with mild dementia with DLB, AD dementia or Parkinson disease (PD) with dementia (PDD), without dementia with PD, and normal controls. Participants indicated the left or right direction of coherently moving dots that were embedded within dynamic visual noise provided by randomly moving dots. The proportion of coherently moving dots was increased or decreased across trials to determine a threshold at which participants could correctly indicate their direction with greater than 80% accuracy. RESULTS: Motion discrimination thresholds of patients with DLB and PDD were comparable and significantly higher (i.e., worse) than those of patients with AD dementia. The thresholds of patients with AD dementia and patients with PD were normal. These results were confirmed in subgroups of patients with DLB/PDD and AD dementia with autopsy-confirmed disease. A motion discrimination threshold greater than 0.23 distinguished between DLB/PDD and AD dementia with 67% sensitivity and 85% specificity. CONCLUSIONS: Differential deficits in detecting direction of simple horizontal motion suggest that dorsal processing stream dysfunction is greater in DLB and PDD than in AD dementia. Therefore, impaired performance on simple visual motion discrimination tasks that specifically engage occipitoparietal brain regions suggests the presence of Lewy body pathology.

Visual search in Dementia with Lewy Bodies and Alzheimer's disease.

Visual search is an aspect of visual cognition that may be more impaired in Dementia with Lewy Bodies (DLB) than Alzheimer's disease (AD). To assess this possibility, the present study compared patients with DLB (n = 17), AD (n = 30), or Parkinson's disease with dementia (PDD; n = 10) to non-demented patients with PD (n = 18) and normal control (NC) participants (n = 13) on single-feature and feature-conjunction visual search tasks. In the single-feature task participants had to determine if a target stimulus (i.e., a black dot) was present among 3, 6, or 12 distractor stimuli (i.e., white dots) that differed in one salient feature. In the feature-conjunction task participants had to determine if a target stimulus (i.e., a black circle) was present among 3, 6, or 12 distractor stimuli (i.e., white dots and black squares) that shared either of the target's salient features. Results showed that target detection time in the single-feature task was not influenced by the number of distractors (i.e., "pop-out" effect) for any of the groups. In contrast, target detection time increased as the number of distractors increased in the feature-conjunction task for all groups, but more so for patients with AD or DLB than for any of the other groups. These results suggest that the single-feature search "pop-out" effect is preserved in DLB and AD patients, whereas ability to perform the feature-conjunction search is impaired. This pattern of preserved single-feature search with impaired feature-conjunction search is consistent with a deficit in feature binding that may be mediated by abnormalities in networks involving the dorsal occipito-parietal cortex.

Kinematics of signature writing in healthy aging.

Forensic document examiners (FDE) called upon to distinguish a genuine from a forged signature of an elderly person are often required to consider the question of age-related deterioration and whether the available exemplars reliably capture the natural effects of aging of the original writer. An understanding of the statistical relationship between advanced age and handwriting movements can reduce the uncertainty that may exist in an examiner's approach to questioned signatures formed by elderly writers. The primary purpose of this study was to systematically examine age-related changes in signature kinematics in healthy writers. Forty-two healthy subjects between the ages of 60-91 years participated in this study. Signatures were recorded using a digitizing tablet, and commercial software was used to examine the temporal and spatial stroke kinematics and pen pressure. Results indicated that vertical stroke duration and dysfluency increased with age, whereas vertical stroke amplitude and velocity decreased with age. Pen pressure decreased with age. We found that a linear model characterized the best-fit relationship between advanced age and handwriting movement parameters for signature formation. Male writers exhibited stronger age effects than female writers, especially for pen pressure and stroke dysfluency. The present study contributes to an understanding of how advanced age alters signature formation in otherwise healthy adults.

Prototype learning and dissociable categorization systems in Alzheimer's disease.

Recent neuroimaging studies suggest that prototype learning may be mediated by at least two dissociable memory systems depending on the mode of acquisition, with A/Not-A prototype learning dependent upon a perceptual representation system located within posterior visual cortex and A/B prototype learning dependent upon a declarative memory system associated with medial temporal and frontal regions. The degree to which patients with Alzheimer's disease (AD) can acquire new categorical information may therefore critically depend upon the mode of acquisition. The present study examined A/Not-A and A/B prototype learning in AD patients using procedures that allowed direct comparison of learning across tasks. Despite impaired explicit recall of category features in all tasks, patients showed differential patterns of category acquisition across tasks. First, AD patients demonstrated impaired prototype induction along with intact exemplar classification under incidental A/Not-A conditions, suggesting that the loss of functional connectivity within visual cortical areas disrupted the integration processes supporting prototype induction within the perceptual representation system. Second, AD patients demonstrated intact prototype induction but impaired exemplar classification during A/B learning under observational conditions, suggesting that this form of prototype learning is dependent on a declarative memory system that is disrupted in AD. Third, the surprisingly intact classification of both prototypes and exemplars during A/B learning under trial-and-error feedback conditions suggests that AD patients shifted control from their deficient declarative memory system to a feedback-dependent procedural memory system when training conditions allowed. Taken together, these findings serve to not only increase our understanding of category learning in AD, but to also provide new insights into the ways in which different memory systems interact to support the acquisition of categorical knowledge.

Apolipoprotein E epsilon4 influences on episodic recall and brain structures in aging pilots.

The apolipoprotein (APOE) epsilon4 allele is associated with cognitive deficits and hippocampal atrophy in nondemented middle-aged and older adults. It is not known to what extent this genetic risk factor for Alzheimer's disease (AD) impacts performance in late middle-aged and older workers in cognitively demanding occupations. This cross-sectional analysis examines brain-cognitive-genetic relationships in actively flying general aviation pilots, half of whom are APOE epsilon4 carriers. Fifty pilots were studied with structural MRI and memory tasks. Average visual paired associate memory recall performance was lower in APOE epsilon4 carriers than non-carriers. Memory performance correlated positively with hippocampal volume, but no structural differences were found in hippocampal or frontal volumes with respect to APOE epsilon4 allele. These results were evident in healthy professionals without any presenting memory problems and without selection for a family history of AD. These findings point to basic memory testing as a sensitive tool for detecting APOE epsilon4-related influences on memory in aging workers.