The effect of Parkinson’s disease subgroups on verbal and nonverbal fluency

Background. Parkinson’s disease (PD) leads to deficits in executive function, including verbal and nonverbal fluency, as a result of compromised frontostriatal circuits. It is unknown whether deficits in verbal and nonverbal fluency in PD are driven by certain subgroups of patients, or how strategy use may facilitate performance. Participants. Sixty-five nondemented individuals with PD, including 36 with right-body onset (RPD; 20 with tremor as their initial symptom, 16 nontremor) and 29 with left-body onset (LPD; 14 with tremor as their initial symptom, 15 nontremor), and 52 normal control participants (NC) took part in the study. Measurements. Verbal fluency was assessed using the FAS and Animals tests. Nonverbal fluency was assessed using the Ruff Figural Fluency Test. Results. Both RPD and LPD were impaired in generating words and in using clustering and switching strategies on phonemic verbal fluency, whereas different patterns of impairment were found on nonverbal fluency depending on the interaction of side of onset and initial motor symptom (tremor vs. nontremor). Strategy use correlated with number of correct responses on verbal fluency in LPD, RPD, and NC. By contrast, on nonverbal fluency, strategy use correlated with correct responses for RPD and LPD, but not for NC. Conclusion. Our findings demonstrate the importance of considering subgroups in PD and analyzing subcomponents of verbal and nonverbal fluency (correct responses, errors, and strategies), which may depend differently on the integrity of dorsolateral prefrontal cortex, inferior frontal cortex, and anterior cingulate cortex.     

Attenuated prefrontal activation during a verbal fluency task in remitted major depression

The aim of the present study was to investigate whether a functional abnormality in the left prefrontal cortex observed in patients with major depression performing a verbal fluency task is present after remission of depression. Functional magnetic resonance imaging was used to study changes in cerebral blood oxygenation in eight remitted patients with major depression and 10 healthy control subjects during a verbal fluency task. Compared to the control subjects, the patients had a reduced response in the left prefrontal cortex (middle frontal gyrus, Brodmann area 10). These findings suggest the presence of dysfunction in the left prefrontal cortex during remission in major depression.     

Putative Tests of Frontal Lobe Function: A PET-Study of Brain Activation During Stroop's Test and Verbal Fluency

Stroop's test and the Verbal Fluency test are commonly argued to be measures of the integrity of the prefrontal cortex. This assumption has only to some degree been confirmed by lesion studies. In the present study, Positron Emission Tomography (PET) with H 2 15 O was used to further validate Stroop's test and the Verbal Fluency as measures of frontal lobe function; both tests were implemented as activation paradigms during scanning of normal middleaged individuals. Stroop interference was found to activate the left anterior cingulate cortex, the supplementary motor cortex, thalamus, and the cerebellum. Although the prominent anterior cingulate activation is in the frontal lobe, it is not prefrontal. Verbal Fluency activated the left inferior frontal cortex and the left dorsolateral prefrontal cortex, the supplementary motor cortex, the anterior cingulate cortex and the cerebellum. These results bring this latter test closer to being a specific test of prefrontal function.     

Putative tests of frontal lobe function: a PET-study of brain activation during Stroop's Test and verbal fluency

Stroop's test and the Verbal Fluency test are commonly argued to be measures of the integrity of the prefrontal cortex. This assumption has only to some degree been confirmed by lesion studies. In the present study, Positron Emission Tomography (PET) with H(2)(15)O was used to further validate Stroop's test and the Verbal Fluency as measures of frontal lobe function; both tests were implemented as activation paradigms during scanning of normal middleaged individuals. Stroop interference was found to activate the left anterior cingulate cortex, the supplementary motor cortex, thalamus, and the cerebellum. Although the prominent anterior cingulate activation is in the frontal lobe, it is not prefrontal. Verbal Fluency activated the left inferior frontal cortex and the left dorsolateral prefrontal cortex, the supplementary motor cortex, the anterior cingulate cortex and the cerebellum. These results bring this latter test closer to being a specific test of prefrontal function.     

An fMRI study of prefrontal dysfunction and symptomatic recovery in schizophrenia

Smee C, Krabbendam L, O’Daly O, Prins A‐M, Nalesnik N, Morley L, Samson G, Shergill S. An fMRI study of prefrontal dysfunction and symptomatic recovery in schizophrenia. Objective: Prefrontal cortical dysfunction has been implicated in the pathophysiology of schizophrenia but it is unclear to what extent these are related to changes in symptomatology as well as task demand. Method: We examined the neural correlates of symptom change and task demand during a longitudinal functional magnetic resonance imaging (fMRI) study using a verbal fluency task with differential task demands in patients with schizophrenia and matched healthy control subjects. The fMRI data were acquired using clustered acquisition technique, enabling ongoing monitoring of behavioural responses, in the patient group on two occasions separated by 6–8 weeks, and the control group at baseline. Results: Positive psychotic symptoms were significantly reduced over the 6–8‐week duration of the study. This change was associated with increased activation within the left middle frontal gyrus and decreased activation of the left precuneus. An interaction between symptom change and task demand was evident in the activation of the left middle frontal gyrus. The decrease in positive symptoms was associated with normalisation of activation in the dorsolateral prefrontal cortex and a decrease in parietal activation during the verbal fluency task. Conclusion: The data supports the role of dysfunctional prefronto‐parietal relationships in the genesis of positive psychotic symptoms.     

Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study.

BACKGROUND: Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder. METHODS: Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls. RESULTS: We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes. CONCLUSIONS: While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.     

Only subtle cognitive deficits in non–bulbar amyotrophic lateral sclerosis patients

Neuropsychological investigations of amyotrophic sclerosis (ALS) patients revealed considerable discrepancies regarding neurocognitive functions. Some, but not all studies have suggested executive dysfunctioning and memory impairment, and there is a wide range of applied neuropsychological tests and results. In this study, we investigated the neuropsychological performance of 15 non–bulbar ALS patients, 14 patients with neuromuscular symptoms, and 15 healthy controls. To avoid confounding effects of motor disability, performance was assessed using exclusively motor–free tests of frontal lobe functioning (specific memory functions, conditional–associative learning, attention, and executive functions). ALS patients exhibited poorer performance in two conditions (semantic and alternating condition, respectively) of the Verbal Fluency Test, suggesting a subtle executive deficit. No deficits were found in tests of memory, conditionalassociative learning, or attention. Assessed mood status was not related to neuropsychological performance.Verbal memory (CVLT) and verbal fluency (lexical condition) were positively associated with duration of disease. Our results support the view that there are only subtle cognitive deficits in ALS patients and we assume a possible effect of practice on cognitive tasks following reduced daily motor activity.     

Cognitive endophenotypes in a family with bipolar disorder with a risk locus on chromosome 4

Objectives: We studied cognitive function in high‐risk relatives belonging to a single extended family showing linkage of bipolar disorder to a locus on chromosome 4. High‐risk relatives were defined as those that carried the risk haplotype of polymorphic markers, identified in a previous linkage study. This family provided a rare opportunity to characterize a neuropsychological endophenotype in a homogeneous sample of relatives with a common genetic risk factor. Methods: Fifteen family members carrying the risk haplotype (eight diagnosed with bipolar disorder or depression and seven with no psychiatric diagnosis), unrelated patients with bipolar disorder (n = 36) and major depressive disorder (n = 40), and healthy control subjects (n = 33) were administered the California Verbal Learning Test, Verbal Fluency Test, Hayling Sentence Completion Test, and Brixton Spatial Anticipation Test to assess verbal memory, verbal fluency, and executive function. Results: Compared with healthy controls, family members carrying the risk haplotype were impaired in indices of memory and executive function. There were no significant differences between unaffected and affected haplotype‐carrying family members in any cognitive measure. Pronounced deficits in the encoding stage of verbal memory and category verbal fluency were evident in individuals with the risk haplotype. Conclusions: Verbal learning and semantic verbal fluency impairments may represent a cognitive endophenotype for both bipolar disorder and major depression in relatives of bipolar disorder patients, as impairment was also present in high‐risk relatives who had not developed any affective disorder symptoms. These findings suggest that impairment in semantic organization may be linked to the genetic aetiology of bipolar disorder.     

A neuropsychological investigation of prefrontal cortex involvement in acute mania

OBJECTIVE: Mania has received little attention from a contemporary neuropsychological perspective despite its clear resemblance to the disinhibition syndrome sometimes seen after frontal brain injury, particularly injury to the inferior aspect of the prefrontal cortex. The purpose of this investigation was to describe the neuropsychological profile of severe acute mania by using a range of tasks selected primarily for the detection of localized neural disruption within the prefrontal cortex. METHOD: Fifteen acutely manic inpatients were compared with 30 nonpsychiatric subjects on tasks from the Cambridge Automated Neuropsychological Test Battery (Tower of London, spatial working memory, intradimensional-extradimensional attentional shift, and rapid visual information processing tasks) and on the Iowa Gambling Task, Stroop Color and Word Test, a verbal fluency task, and the California Verbal Learning Test. RESULTS: Discriminant function analysis identified deficits in sustained attention (on the rapid visual information processing task) and verbal learning (on the California Verbal Learning Test) as the best indicators of manic performance, rather than deficits on any of the tests of executive functioning. The model correctly classified 91% of subjects overall and 87% of manic subjects. Manic patients did not resemble patients with ventromedial prefrontal cortex damage in their performance on the Iowa Gambling Task. CONCLUSIONS: Acute mania is characterized by core deficits in verbal memory and sustained attention against a background of milder impairments in functions that are traditional measures of prefrontal cortex integrity (attentional set shifting, planning, working memory). The data do not implicate ventral prefrontal cortex disruption as a locus of pathology in acute mania. Verbal memory and sustained attention deficits may relate differentially to the state and trait characteristics of bipolar disorder.     

Differential impairment in semantic, phonemic, and action fluency performance in Friedreich's ataxia: possible evidence of prefrontal dysfunction.

This study examined phonemic (letters), semantic (animals) and action verbal fluency cues in twenty-four patients with FRDA, and twenty matched healthy control subjects. The Action Fluency Test (AFT) is a newly-developed verbal fluency cue that consists in asking the subject to rapidly generate verbs. Given the high presence of dysarthria and cognitive slowness in FRDA patients, control tasks were administered in order to dissociate motor/articulatory impairment and cognitive slowness from verbal fluency deficit. Results showed that patients and control subjects performed similarly on the semantic fluency task. In contrast, patients performed significantly poorer on phonemic and action fluency tests. Correlational analyses showed that the deficits cannot be attributed to dysarthria or cognitive slowness. Although executive processes are necessary for initiating and monitoring all verbal fluency tasks, phonemic and action fluency may place a greater burden on strategic processes, given that they require a more unusual type of lexicon search. Thus, the deficits found occur in tasks that require greater executive/prefrontal control. This impairment might be the result of an affectation of cerebellum-prefrontal cortex connections, although the possibility of a primary prefrontal dysfunction remains to be investigated.     

Modulation of verbal fluency networks by transcranial direct current stimulation (tDCS) in Parkinson’s disease

BackgroundVerbal fluency relies on the coordinated activity between left frontal and temporal areas. Patients with Parkinson’s disease (PD) present phonemic and semantic fluency deficits. Recent studies suggest that transcranial direct current stimulation (tDCS) enhances adaptative patterns of brain activity between functionally connected areas.ObjectiveThe aim of this study was to assess the differences in the effects induced by tDCS applied to frontal and temporo-parietal areas on phonemic and semantic fluency functional networks in patients with PD.MethodSixteen patients were randomized to receive tDCS to left dorsolateral prefrontal cortex (DLPFC) and left temporo-parietal cortex (TPC) in a counterbalanced order. Immediately following stimulation, patients underwent a verbal fluency paradigm inside a fMRI scanner. Changes induced by tDCS in activation and deactivation task-related pattern networks were studied using free-model independent component analyses (ICA).ResultsFunctional connectivity in verbal fluency and deactivation task-related networks was significantly more enhanced by tDCS to DLPFC than to TPC. In addition, DLPFC tDCS increased performance on the phonemic fluency task, after adjusting for baseline phonemic performance.ConclusionsThese findings provide evidence that tDCS to specific brain regions induces changes in large scale functional networks that underlay behavioural effects, and suggest that tDCS might be useful to enhance phonemic fluency in PD.     

Basal-corticofrontal circuits in schizophrenia and obsessive-compulsive disorder: a controlled, double dissociation study.

BACKGROUND: Several lines of research suggest that prefrontal cortex dysfunctions observed in obsessive compulsive disorder (OCD) and schizophrenia (SKZ) are linked to two partially independent neuroanatomic systems: the ventromedial prefrontal cortex and the dorsolateral prefrontal cortex, with different neuroanatomic connections, including the striatum. The primary aim of this study was to test this hypothesis using a double dissociation study of neuropsychological tasks performance of the dorsolateral prefrontal cortex and ventromedial prefrontal cortex. METHODS: We administered the Wisconsin Card Sorting Test, the Gambling Task, and the four-disk version of the Tower of Hanoi to 110 SKZ and 67 OCD patients and 56 control subjects. RESULTS: A clear double dissociation of Wisconsin Card Sorting Test and Gambling Task performances was found, with SKZ patients performing the Wisconsin Card Sorting test significantly worse than OCD patients and control subjects and OCD patients performing the Gambling Task significantly worse than SKZ and control subjects. Both SKZ and OCD patients performed the Tower of Hanoi significantly worse than control subjects. CONCLUSIONS: Results from our double dissociation study confirm the hypothesis of involvement of different frontal lobe subsystems within basal-corticofrontal circuits function in SKZ and OCD.     

Temporally anticorrelated brain networks during working memory performance reveal aberrant prefrontal and hippocampal connectivity in patients with schizophrenia

Functional neuroimaging studies on cognitive dysfunction in schizophrenia have suggested regional brain activation changes in the dorsolateral prefrontal cortex and the medial temporal lobe. However, less is known about the functional coupling of these areas during cognitive performance. In this study, we used functional magnetic resonance imaging, a verbal working memory (WM) task and multivariate statistical techniques to investigate the functional coupling of temporally anticorrelated neural networks during cognitive processing in patients with schizophrenia (n = 16) compared to healthy controls (n = 16). Independent component analysis identified 18 independent components (ICs) among which two ICs were selected for further analyses. These ICs included temporally anticorrelated networks which were most highly associated with the delay period of the task in both healthy controls and patients with schizophrenia. Functional network abnormalities in patients with schizophrenia were detected within a “task-positive” lateral frontoparietal network, where increased functional connectivity was found in bilateral dorsolateral prefrontal regions. In addition, aberrant functional coupling of the hippocampal cortex in patients with schizophrenia was detected within a “task-negative” medial frontotemporal network. In patients with schizophrenia, functional connectivity indices in the left dorsolateral prefrontal cortex and the right hippocampal cortex were positively correlated with accuracy during the WM task, while the connectivity strength in the right dorsolateral prefrontal cortex was negatively correlated with measures of symptom severity. These data suggest that within two temporally anticorrelated network states, patients with schizophrenia exhibit increased and persistent dorsolateral prefrontal and hippocampal connectivity during WM performance.     

抑郁症对海马及背外侧前额叶皮质神经元变与1HMRS表现及明尼苏达多项个性测量的相关性

Background and Purpose The present study was undertaken to elucidate neuro-structural and neuro-chemical characteristics of hippocampi and dorsolateral prefrontal cortex in patients with depressive disorder by using 1H-MRS and to study the association between 1H-MRS and Minnesota Mutiphasic Personality Inventory-2 in relation to the severity of the depression.. Methods Magnetic resonance imaging and 1H-MRS were performed on 33 patients with depressive disorder and age-18 and gender-matched healthy controls. Minnesota Mutiphasic Personality Inventory-2 test was performed on all depressive subjects and control subjects. Results Magnetic resonance imaging and 1H-MRS examinations showed widened sulcus and cisterns as well as the absence of abnormal signal in depressive patients. In addition, the N-acetyl aspartate/total creatine ratios in the bilateral hippocampi and dorsolateral prefrontal cortex were significantly lower in depressive patients than in the control subjects (P<0.01). In contrast, the choline-containing compounds/total creatine ratios in dorsolateral prefrontal cortex were remarkably higher in depressive patients than in the control subjects (Left: P<0.01, Right: P<0.01), the ratios of which were also significantly positively correlated with the depression scores of the patients assessed by Minnesota Mutiphasic Personality Inventory-2 scale (Right: r = 0.8787, Left: r = 0.9347). Conclusions 1H-MRS can be used to reveal reduced neuronal viability or function in the hippocampus and dorsolateral prefrontal cortex and altered membrane phospholipid metabolism in the dorsolateral prefrontal cortex in patients with depressive disorder. The 1H-MRS findings partially reflect the severity of the depressive disorder.     

The special involvement of the rostrolateral prefrontal cortex in planning abilities: an event-related fMRI study with the Tower of London paradigm

Planning abilities are essential for the successful management of everyday life activities. Although several neuroimaging studies provide evidence that the prefrontal cortex is crucially involved in planning, the differential roles of its subregions are still a matter of debate. The aim of this study was to investigate the neural correlates of planning by focusing on the functional differentiation between the dorsolateral and rostrolateral prefrontal cortex using the Tower of London (ToL) task and a parametric event-related functional MRI design. In order to control for activations unspecific to planning, two control conditions were presented, which were matched for the length of single events in the ToL task. Seventeen right-handed healthy subjects participated in this study. All statistics were reported with corrections for multiple comparisons (p < 0.05). Compared to control conditions, activations in the ToL task were observed in the dorsolateral prefrontal cortex bilaterally, the right ventrolateral and left rostrolateral prefrontal cortex along with the thalamus, as well as in the parietal and premotor cortex bilaterally. Task complexity dependent analyses revealed that only the left rostrolateral prefrontal cortex showed a BOLD signal increase over the four planning levels, which could not be observed in the control conditions. Hence, current findings suggest that planning involves an extensive fronto-parieto-thalamic network. Within this network, the rostrolateral prefrontal cortex seems to be the only region that is exclusively reactive to planning specific processes, which we described in terms of simultaneous monitoring of internally generated and externally presented information.     

Verbal fluency and executive dysfunction in amyotrophic lateral sclerosis (ALS)

Neuropsychological investigations of amyotrophic lateral sclerosis (ALS) patients have revealed variable results on specific tests, despite a similar overall cognitive profile of predominantly executive dysfunction with some evidence of memory impairment. The most striking and consistent deficit is found using tests of verbal fluency. The current investigation explored why verbal fluency is particularly sensitive to the impairment in ALS, by investigating some of the underlying cognitive processes: (i) intrinsic response generation; (ii) phonological loop functions; and (iii) simple word retrieval. Twenty-two ALS patients and 25 healthy controls were investigated. The battery included: (i) written and spoken letter-based fluency, category fluency, design fluency; (ii) the Phonological Similarities effect and Word Length Effect; and (iii) computerised sentence completion and confrontational naming. The tests were designed to control for motor speed and to accommodate for the range of disabilities that are present in ALS patients. Significant impairments were found on some tests of intrinsic response generation, namely the Written Verbal Fluency Test, Category Fluency Test (generation of animal names) and Design Fluency Test. Phonological loop functions appeared to be intact with evidence of both the Phonological Similarities and Word Length Effects, but the ALS patients displayed significantly reduced working memory capacity. No deficits were found on tests of simple word retrieval. The findings indicate that verbal fluency impairments in ALS patients result from a higher order dysfunction, implicating deficits in the supervisory attentional system or central executive component of working memory, and are not caused or exaggerated by an impairment in phonological loop functions or in primary linguistic abilities. The study also demonstrates the importance of controlling for differences in motor speed, which may have served to exaggerate the presence of cognitive deficits in ALS patients reported by some other studies.     

Impairments in an early stage of the decision-making process in patients with ventromedial prefrontal damage: preliminary results

Lesions of the ventromedial prefrontal cortex can result in a deficient decision-making behavior. So far, most experimental results in the neuropsychological decision-making research have been obtained with gambling tasks. Due to their high complexity, it is difficult to evaluate the underlying processes of the decision-making deficits. The aim of this study was to assess if patients with ventromedial prefrontal damage compared to patients with dorsolateral prefrontal damage and controls show a deficit in an early stage of the decision-making process. Nine patients with ventromedial prefrontal damage, three with dorsolateral prefrontal damage, and eleven healthy controls were tested with a newly developed decision task in which they had to search actively for the information they needed for their decisions. Our results show that patients with ventromedial prefrontal damage compared to the brain-lesioned dorsolateral prefrontal control group and healthy controls searched less for information with regard to risk defusing operators or consequences of their decisions indicating impairment already in the early stage of the decision-making process.     

Attenuated left prefrontal activation during a verbal fluency task in patients with depression

Functional neuroimaging studies on patients with depression have found abnormal activity in the left prefrontal and anterior cingulate cortex compared with healthy controls. Other studies have shown that these regions become active in healthy subjects during verbal fluency tasks, while patients with depression show impaired performance on such tasks. We used functional magnetic resonance imaging to investigate changes in cerebral blood oxygenation associated with a verbal fluency task in depressed patients and healthy volunteers. In contrast to 10 age- and sex-matched healthy control subjects who activated the left prefrontal cortex and the anterior cingulate cortex during word generation, 10 depressed subjects showed attenuated activation in the left prefrontal cortex and did not show significant activation in the anterior cingulate cortex. These findings suggest that impaired performance during verbal fluency task in depressed patients is associated with abnormal neural responses within these regions.     

Implicit sequence‐specific motor learning after subcortical stroke is associated with increased prefrontal brain activations: An fMRI Study

Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence‐specific motor learning as compared to general improvements in motor control. Nine healthy participants and nine individuals with chronic, right focal subcortical stroke performed a continuous joystick‐based tracking task during an initial functional magnetic resonance images (fMRI) session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence‐specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequence during early practice and again at the retention test. Both groups demonstrated implicit sequence‐specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased blood oxygenation level dependent (BOLD) response in left dorsal premotor cortex (PMd; BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence‐specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal‐based attentional network for implicit motor learning after stroke. This study is the first to highlight the importance of the prefrontal cortex for implicit sequence‐specific motor learning after stroke. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

On the nature of memory disturbance in multiple sclerosis

Abstract

Thirty-seven patients with multiple sclerosis (MS) were compared to 26 normal controls of equivalent age, education, and verbal intelligence on measures of verbal learning and memory (Digit Span and Supraspan, Brown-Peterson Distractor Task, Selective Reminding Test, Story Recall, and Free Verbal Recall) and verbal fluency (Letter and Animal Fluency). The MS patients exhibited deficits on measures of secondary (long-term) memory and verbal fluency, but performed normally on measures of primary (short-term) memory, recognition memory, and rate of forgetting from secondary memory. These results suggest that the memory disturbance in MS results primarily from an impaired ability to access information from secondary memory, while encoding and storage capacity is intact. Degree of memory impairment was unrelated to length of illness, severity of disability, or self-reported depression.