The Visual Spatial Learning Test: differential impairment during the premanifest and manifest stages of Huntington's disease.

Visual spatial memory was assessed using the Visual Spatial Learning Test (VSLT) in individuals with mild to moderate Huntington's disease (HD), pre-manifest gene carriers for HD, and demographically similar controls. The VSLT has been demonstrated to be a valid, normed measure of non-verbal memory involving minimal motoric responses. The VSLT assesses immediate and delayed memory for designs, positions of the designs, and design/position associations. The HD group was significantly impaired (p < .05) relative to both the control and Pre-HD groups on immediate and delayed memory for the designs, positions, and design/position associations. Although there were no differences between the Pre-HD and control groups on immediate or delayed memory for designs or positions, the Pre-HD group was significantly impaired (p < .05) relative to the control group on immediate and delayed memory for design/position associations. The results offer novel insight into a relatively unexamined memory deficit that may occur in gene carriers for HD prior to phenoconversion. The data indicate that the VSLT may be a useful measure of visuospatial memory during the premanifest and manifest stages of HD.

The utility of the Mattis Dementia Rating Scale in Parkinson's disease mild cognitive impairment.

BACKGROUND: The Movement Disorders Society (MDS) recently proposed guidelines for diagnosis of mild cognitive impairment in Parkinson's disease (PD-MCI) that includes two assessment levels: abbreviated (Level I) and comprehensive (Level II). The aim of this study was to determine the utility of the Mattis Dementia Rating Scale (MDRS), a recommended Level I test, for detecting Level II PD-MCI diagnosis. METHODS: The study sample included 30 patients diagnosed with PD-MCI based on Level II MDS criteria and 68 PD patients with normal cognition (PD-NC). Receiver operator curve (ROC) analyses were generated to measure the sensitivity and specificity of various MDRS cutoff scores. To examine the utility of the MDRS as a screening tool, the optimal cutoff point was defined as the lowest value providing ≥80% sensitivity. For use of the MDRS as a diagnostic tool, the optimal cutoff point was defined as the highest value providing ≥80% specificity. RESULTS: ROC analyses showed that the optimal MDRS cutoff score for screening purposes and diagnostic purposes were ≤140 and ≤137, respectively. However, an examination of sensitivity/specificity values for the screening cutoff scores suggested that a total score of ≤139 for screening purposes yielded a better balance between sensitivity (77%) and specificity (65%). CONCLUSIONS: In a clinical setting, in which detection of PD-MCI may be important, a total MDRS score of ≤139 can be used to detect PD-MCI. In research and other settings in which diagnostic certainty is more important, a score of ≤137 may be more useful.

Instrumental activities of daily living are impaired in Parkinson's disease patients with mild cognitive impairment.

OBJECTIVE: Although it is well known that Parkinson's disease (PD) with dementia results in functional decline, little is known about the impact of mild cognitive impairment in PD (PD-MCI) on day-to-day functioning. METHOD: Forty-one individuals with PD-MCI, 56 PD patients with normal cognition (PD-NC), and 47 healthy older adults were administered two performance-based measures of instrumental activities of daily living (IADLs) that evaluated medication and financial management. Informants of the PD patients were also administered an IADL questionnaire. RESULTS: There were no significant differences between PD-NC and healthy older adults on the performance-based measures of medication and financial management. However, PD-MCI patients demonstrated significantly lower scores on the performance-based measures of medication and financial management compared with healthy older adults. PD-MCI patients were also impaired compared with PD-NC patients on performance-based medication management, but no difference between these groups was observed for ability to manage finances. Performance-based financial and medication management did not correlate with scores on neuropsychological measures in PD-MCI patients. PD-MCI and PD-NC patients showed comparable scores on the informant-based IADL questionnaire. CONCLUSIONS: Performance-based measures of IADLs, particularly medication management ability, are sensitive to subtle functional declines in PD-MCI. Although impairment in performance-based measures is associated with cognitive status in PD, IADLs may be a separate domain of functioning from cognitive functioning in PD-MCI as these measures did not correlate with performance on the neuropsychological measures. Overall, performance-based assessment of IADLs may add to the clinical evaluation of PD-MCI.

"Forgetting to remember" in Huntington's disease: a study of laboratory, semi-naturalistic, and self-perceptions of prospective memory.

Prospective memory (PM) is dependent on executive processes known to be impaired in Huntington's disease (HD); however, no study to the authors' knowledge has investigated PM in this group. We examined performance-based, semi-naturalistic, and self-reported PM in 20 individuals diagnosed with mild-moderate HD and 20 demographically similar controls. Relative to controls, HD participants demonstrated significantly lower scores in time-based PM, event-based PM (at a trend level), and the semi-naturalistic PM trial, all of which were marked by omission errors. HD participants demonstrated comparable recognition memory for the PM intentions relative to controls. HD and control participants also showed comparable scores in self-reported PM complaints. The results suggest that HD is associated with deficits in the strategic aspects of PM. HD-associated PM deficits also are evident in real-world situations, which may relate to an apparent meta-memory deficit for PM functioning as indicated by HD participants' overestimation of their PM performance on self-report.

Predictors of performance-based measures of instrumental activities of daily living in nondemented patients with Parkinson's disease.

Few studies have examined instrumental activities of daily living (iADLs) in nondemented Parkinson's disease (PD), and the majority of these studies have used report-based measures, which can have limited validity. The present study had two main goals: (a) to examine the performance of nondemented PD patients on two performance-based measures of iADLs, which are considered more objective functional measures, and (b) to examine the cognitive, motor, and psychiatric correlates of iADL impairment in PD. Ninety-eight nondemented PD patients and 47 healthy older adults were administered performance-based measures that assess the ability to manage medications (Medication Management Ability Assessment) and finances (University of California, San Diego, UCSD, Performance-based Skills Assessment), the Mattis Dementia Rating Scale to assess global cognitive functioning, the Unified Parkinson's Disease Rating Scale Part III to assess motor symptom severity, and the Geriatric Depression Scale to assess depressive symptoms. Nondemented PD patients demonstrated significantly impaired scores relative to the healthy comparison group on the performance-based measure of financial management, but there were no significant group differences in medication management. Global cognitive functioning, motor severity, and depressive symptoms did not correlate with scores on either of the functional measures, except for a small correlation between depressive symptoms and financial management. The two performance-based measures of iADL functioning did not correlate with one another. These findings suggest that medication and financial management may not be predicted based on global cognitive functioning and that iADLs may not be represented by a single construct. Furthermore, these findings suggest the potential need for a multidimensional approach to assessing iADLs.

Temporal sequence learning in healthy aging and amnestic mild cognitive impairment.

UNLABELLED: BACKGROUND/STUDY CONTEXT: Temporal sequence learning is a critical aspect of episodic memory that may be dependent on the temporal and frontal lobes. Because amnestic mild cognitive impairment (aMCI) and normal aging may result in changes within the temporal and frontal lobes, the present study investigated temporal sequence learning in patients with aMCI, cognitively normal older adults, and young adults. METHODS: On each trial of a temporal sequence task, circles appeared one at a time at the end of each arm of a computerized radial eight-arm maze. Participants were asked to reproduce the temporal sequence by placing numbered circles (1 to 8) on the arms of the eight-arm maze. Participants were presented with the same fixed sequence on each trial until the sequence was replicated without any errors, or until 15 trials were presented. RESULTS: Individuals with aMCI required significantly more trials to learn the temporal sequence compared with older adults (p < .05). Older adults required significantly more trials to learn the sequence than young adults (p < .05). Older adults and individuals with aMCI committed significantly more Trial 1 errors (p < .05) than young adults; however, there were no significant differences between the aMCI and older adult groups on Trial 1. CONCLUSION: The results suggest that temporal sequence learning deficits are detectable in aMCI. These deficits may disrupt a number of cognitive processes, such as episodic memory, that are important for the execution of daily activities. The results suggest that although temporal sequence learning declines with normal aging, this decline is greater in individuals who have a diagnosis of aMCI and are at higher risk for developing Alzheimer's disease.

Visual object pattern separation varies in older adults.

Young and nondemented older adults completed a visual object continuous recognition memory task in which some stimuli (lures) were similar but not identical to previously presented objects. The lures were hypothesized to result in increased interference and increased pattern separation demand. To examine variability in object pattern separation deficits, older adults were divided into impaired and unimpaired groups based on performance on a standardized serial list-learning task. Impaired older adults showed intact recognition memory, but were impaired relative to young and unimpaired older adults when identifying similar lure stimuli, demonstrating that object pattern separation varies in older adults.

Visuospatial temporal order memory deficits in older adults with HIV infection.

OBJECTIVE: To compare temporal order memory in older adults with and without human immunodeficiency virus (HIV) infection. BACKGROUND: The frontal and temporal lobes play a key role in temporal order memory for items in a sequence. HIV-associated episodic memory deficits correlate with damage to neocortical interneurons in the fronto-striato-thalamo-cortical pathway and with atypical activation of the medial temporal lobes. Therefore, temporal order memory may be sensitive to neuropathological changes in individuals with HIV. METHODS: In this study, 50 HIV-seropositive individuals aged ≥ 50 years and 50 seronegative controls performed a computerized visuospatial temporal order memory task. During the sample phase of each trial, participants were shown circles presented 1 at a time in a random sequence at the end of each of the 8 arms of a radial maze. During the choice phase, they were shown the maze with a circle at the ends of 2 of the arms and asked which circle had appeared earlier than the other in the original sequence. RESULTS: Performance in both groups improved as a function of greater temporal separation between circle presentations. However, the HIV group had significantly worse memory impairment across all temporal separations, and the impairment was independently associated with clinical deficits in executive function and delayed retrospective memory. CONCLUSIONS: Our results extend prior findings that HIV is associated with deficits in strategic aspects of memory encoding and retrieval. The neural mechanisms warrant further research, as do potential impacts on everyday function, eg, adherence to antiretroviral drug regimens.

The effect of interference on temporal order memory in premanifest and manifest Huntington's disease.

BACKGROUND: Frontal-striatal dysfunction has been linked to cognitive impairment in Huntington's disease (HD). The frontal lobes play a role in memory for the temporal order in which items occur in a sequence. However, little is known about temporal order memory in HD or how it may be affected by interference. OBJECTIVE: The study assessed temporal order memory in patients with manifest HD (n = 20), premanifest gene carriers for HD (Pre-HD; n = 18), and controls (n = 25) using a computerized radial 8-arm maze. METHODS: On the sample phase of each trial, participants viewed a random sequence of circles appearing one at a time at the end of each arm. On the choice phase, participants viewed two sample phase circles and chose the circle occurring earliest in the sequence. Manipulations of the temporal lag (defined as the number of circles occurring in the sample phase sequence between the two choice phase circles) were conducted to systematically vary interference. Temporally proximal lags were hypothesized to generate more interference relative to temporally distal lags. RESULTS: The Pre-HD group was significantly impaired (p < 0.05) compared to controls on proximal temporal lags (high interference) but matched controls on distal lags (low interference). HD patients improved as a function of increased lag but demonstrated significant impairments (p < 0.05) across lags relative to controls. CONCLUSIONS: Temporal order memory is differentially affected by interference during the premanifest and manifest stages of HD. The study identifies a fundamental, yet relatively unexamined, deficit associated with HD.

Postural limits of stability in premanifest and manifest Huntington's disease.

BACKGROUND: Huntington's disease (HD) is associated with neuronal death in basal ganglia circuits important for postural control. Despite evidence of postural instability associated with HD, postural control at the limits of stability has not been investigated in this disease. OBJECTIVE: To use computerized dynamic posturography to measure postural control at the limits of stability during the premanifest and manifest stages of HD. METHODS: Patients with manifest HD, premanifest gene carriers, and matched controls stood on mechanically locked force plates while viewing a computer screen. The participant's estimated center of gravity was represented on the screen as a cursor along with eight target icons arranged in a circular pattern at the theoretical edge of limits of stability. On each trial, one of the eight targets was highlighted and the participant was instructed to control the cursor by rapidly shifting his/her weight in the direction of the target. Measures included reaction time, movement velocity, endpoint excursion, maximum excursion, and directional control. RESULTS: Analysis of variance revealed significant impairment on endpoint excursion, maximum excursion, and directional control (p≤0.001) in the Huntington's disease group, but not in the premanifest gene carrier group as compared to controls. No differences were found on reaction time or movement velocity measures. Group signal to noise ratios also were examined for the measures. CONCLUSIONS: HD patients, but not premanifest gene carriers, showed impaired postural control at the limits of stability. Impaired performance in HD patients has potential functional consequences including increased risk of falling during weight-shifting activities.

Prospective memory deficits are associated with poorer everyday functioning in Parkinson's disease.

Although individuals with Parkinson's disease (PD) evidence moderate deficits in prospective memory (PM), it is not known whether PM deficits confer an increased risk of poorer everyday functioning. In the current study, 33 individuals with PD and 26 demographically similar normal controls (NC) were administered performance-based and self-report measures of PM and everyday functioning, including medication and financial management. As compared to NC, PD participants demonstrated significantly lower scores on performance-based measures of PM and financial capacity, worse performance at a trend level on performance-based medication management and endorsed significantly greater self-reported declines in PM and instrumental activities of daily living (iADLs). In the PD sample, the laboratory measure of PM significantly correlated with performance-based measures of financial capacity and medication management and a self-report measure of medication management. Self-reported PM failures significantly correlated with perceived declines in iADLs, worse medication management, and poorer health-related quality of life. Although future studies are needed to examine the incremental ecological validity of PM in PD, findings from this study extend prior research by providing preliminary evidence that PM impairment may play a significant role in a range of critical everyday functions in PD.

The effect of interference on temporal order memory for random and fixed sequences in nondemented older adults.

Two experiments tested the effect of temporal interference on order memory for fixed and random sequences in young adults and nondemented older adults. The results demonstrate that temporal order memory for fixed and random sequences is impaired in nondemented older adults, particularly when temporal interference is high. However, temporal order memory for fixed sequences is comparable between older adults and young adults when temporal interference is minimized. The results suggest that temporal order memory is less efficient and more susceptible to interference in older adults, possibly due to impaired temporal pattern separation.

Age-related source memory deficits persist despite superior item memory.

Source and item memory for faces of former United States Presidents were assessed in nondemented older adults over 65 years of age (n = 20) and young adults 18 to 25 years of age (n = 20). During the study phase, a male and a female source each presented pictures of faces to the participant one at a time. To assess source memory, the participant was asked to indicate whether a face from the study phase was presented by the male or female. To assess item memory, a study phase face and distractor face were presented and the participant was asked to indicate which was presented previously. Older adults displayed significantly better item memory for the faces of presidents compared to young adults. However, despite showing superior item memory, source memory still was impaired in older adults compared to young adults. The ability of older adults to efficiently integrate source and item information may be compromised to such a large extent that enhanced item memory does not appear to minimize or negate age-related source memory deficits. The findings demonstrate the robust effects of aging on source memory.

Behavioral measures of saccade latency and inhibition in manifest and premanifest Huntington's disease.

Initiation and inhibition of saccadic eye movements has been shown to be impaired in patients with Huntington's disease (HD) and premanifest gene carriers (PMGC), and may provide biomarkers useful in tracking phenotypic change. Computerized behavioral tests of prosaccade latency and disinhibition presented to 31 non-gene carriers (NGC), 25 PMGC, and 12 HD patients. These tests provided quantitative performance measures without use of eye-tracking equipment. Significant differences on saccade tests were found, with PMGC intermediate between NGC and HD patients. Saccade latency discriminated PMGC from NGC, whereas saccade disinhibition discriminated PMGC from HD patients. Results suggest utility of behavioral saccade measures as premanifest indicators of phenoconversion in HD.

The effects of aging on memory for sequentially presented objects in rats.

The current study investigated memory for sequentially presented objects in young rats 6 months old (n = 12) and aged rats 24 months old (n = 12). Rats were tested on a task involving three exploratory trials and one probe test. During the exploratory trials, the rat explored a set of three sequentially presented object pairs (A-A, B-B, and C-C) for 5 min per pair with a 3-min delay between each pair. Following the exploratory trials, a probe test was conducted where the rat was presented simultaneously with one object from the first exploratory trial (A) and one object from the third exploratory trial (C). Results from the exploratory trials showed no significant age-related differences in exploration, indicating that 24-month-old rats explored the object pairs as much as 6-month-old rats. The probe test demonstrated that 6-month-old rats spent significantly more time exploring object A compared to object C, indicating that young rats show intact temporal order memory for the exploratory trial objects. However, 24-month-old rats showed no preference for object A and spent a relatively equal amount of time exploring objects A and C. The results suggest that temporal order memory declines as a result of age-related changes in the rodent brain. The findings also may reflect differences in attraction to objects with different memory strengths. Since age-related differences were not detected during the exploratory trials, age-related differences on the probe trial were not due solely to decreased exploration, motivation, or locomotion.

Developmental differences in memory for cross-modal associations.

Associative learning is critical to normal cognitive development in children. However, young adults typically outperform children on paired-associate tasks involving visual, verbal and spatial location stimuli. The present experiment investigated cross-modal odour-place associative memory in children (7-10 years) and young adults (18-24 years). During the study phase, six odours were individually presented and paired with one of 12 spatial locations on a board. During the test phase, participants were presented with the six stimuli individually and were asked to place each stimulus on the correct spatial location. Children committed significantly more errors on the odour-place task than did young adults. However, item recognition memory for the odours or spatial locations involved in the odour-place associative memory task was similar between children and young adults. Therefore, poor odour-place associative memory in children did not result from impaired memory for the individual odours or spatial locations involved in the associations. The results suggest that cross-modal associative memory is not fully developed in children.

Age-related changes in associative learning for olfactory and visual stimuli in rodents.

Memory for olfactory stimuli may be particularly affected by age-related brain changes in humans and may be an early indicator of cognitive impairment and Alzheimer's disease. Studies involving rats have offered insights into impaired cognition in aged animals, but few have examined odor memory. Therefore, it is unclear whether aged rats are a good model for possible age-related changes in odor memory in humans. Young (6-month-old) and old (24-month-old) rats were tested on associative learning tasks involving visual and olfactory stimuli. The first task examined age-related differences in discrimination and reversal learning for olfactory and visual stimuli; the second task utilized an associative contextual learning task involving olfactory and visual cues. Although old rats were able to perform the olfactory and visual discrimination tasks as well as young rats, old rats displayed significant age-related impairment on the reversal learning and contextual learning tasks. The results suggest that aging may have a similar deleterious effect on odor memory in rats and in humans. The findings may have important implications for the selection of memory paradigms for future research studies on aging. In addition, the use of an animal model to investigate the effects of aging on odor memory will allow researchers the ability to investigate how age-related neuroanatomical and neurochemical changes may result in impaired odor memory.

Temporal order memory deficits prior to clinical diagnosis in Huntington's disease.

The current study examined temporal order memory in preclinical Huntington's disease (pre-HD). Participants were separated into less than 5 years (pre-HD near) and more than 5 years (pre-HD far) from estimated age of clinical diagnosis. Participants completed a temporal order memory task on a computerized radial eight-arm maze. On the study phase of each trial, participants viewed a random sequence of circles appearing one at a time at the end of each arm. On the choice phase, participants viewed two circles at the end of the study phase arms and chose the circle occurring earliest in the sequence. The task involved manipulations of the temporal lag, defined as the number of arms occurring in the sample phase sequence between the two choice phase arms. Research suggests that there is more interference for temporally proximal stimuli relative to temporally distal stimuli. There were no significant differences between the pre-HD far group and controls on the temporal order memory task. The pre-HD near group demonstrated significant impairments relative to the other groups on closer temporal lags, but were normal on the furthest temporal lag. Therefore, temporal order memory declines with increased temporal interference in pre-HD close to estimated diagnosis of HD.

Visual object pattern separation deficits in nondemented older adults.

Young and nondemented older adults were tested on a continuous recognition memory task requiring visual pattern separation. During the task, some objects were repeated across trials and some objects, referred to as lures, were presented that were similar to previously presented objects. The lures resulted in increased interference and an increased need for pattern separation. For each object, the participant was asked to indicate whether (1) this was the first time the object was seen (new), (2) the object was seen previously (old), or (3) the object was similar to a previous object (similar). Older adults were able to correctly identify objects as old or new as well as young adults; however, older adults were impaired when identifying lures as similar. Therefore, pattern separation may be less efficient in older adults resulting in poorer recognition memory performance when interference is increased.

Differential effects of normal aging on memory for odor-place and object-place associations.

Odor-place and object-place associative memory were compared in healthy older (over the age of 65) and young (18 to 25 years of age) adults. Twelve spatial locations were defined on a tabletop board. Either six odors or six objects were presented one at a time and each was paired with a location on the board. The participant then was presented with each stimulus individually and asked to place it in its paired location. Older adults showed impaired odor-place associative memory but unimpaired object-place memory compared to young adults. Item recognition memory for the individual stimuli or locations used on the associative memory task was similar in both groups. The results suggest that odor-place associative memory is particularly affected by age-related brain changes.