Intensity of recreational physical activity throughout life and later life cognitive functioning in women

Long-term physical activity may affect risk of cognitive impairment but few studies have examined later life cognition in relation to intensity of life-long physical activity. We examined the associations between the intensity of long-term recreational physical activity and neuropsychological functioning in 90 healthy postmenopausal women on tests found to be useful in the early identification of dementia. Information was collected about their participation in strenuous and moderate activities between high school and menopause. Summary measures of long-term strenuous and moderate activity were constructed for each participant. All analyses were adjusted for relevant covariates. The six linear regression analyses showed significant positive associations between moderate activity and Wechsler Adult Intelligence Scale Revised (WAIS-R), Digit Span backward, WAIS-R Digit Symbol, and Trail Making Test Part B. Significant negative relationships were found between strenuous activity and Rey Auditory Verbal Learning Test delayed verbal recall, Complex Figure Test delayed visual memory, WAIS-R Digit Span backward, category fluency, and WAIS-R Digit Symbol. The associations found in the present study suggest that while moderate activity may be protective, long-term strenuous activity before menopause may lower cognitive performance later in life. These results support further investigation of the effects of life-long exercise intensity on cognition in later life.     

Attention and executive control predict Alzheimer disease in late life: results from the Berlin Aging Study (BASE).

OBJECTIVE: Longitudinal studies of neuropsychological changes in the preclinical phase of Alzheimer disease (AD) have yielded mixed results. Although some studies report tests of episodic memory, others report tests of attention and executive functions as reliable predictors of subsequent AD. Following theoretical models of neuropsychological processes before AD onset, the authors examined the predictive value of attention and executive function in the preclinical phase of AD in old age. METHODS: Authors studied the cognitive performance of 187 initially normal participants of the Berlin Aging Study, a community-based representative sample of Berlin citizens age 70 to 103, over a period of 4 years. Tests of attention and executive function (Digit Letter Test, Trailmaking Part B Test, Digit Symbol Substitution Test, and Identical Pictures Test) and of learning and recall functions (Activity Recall, Memory for Text, and Paired-Associate Learning) were administered at baseline. Diagnosis of AD was made according to NINCDS-ADRDA criteria (probable AD). Receiver operating characteristics curve analyses and Cox regression analyses were used to assess the diagnostic accuracy and predictive value of the neuropsychological tests at baseline for incident AD after 4 years. RESULTS: After 4 years, 15 participants had developed AD. Tests of attention and executive function discriminated best between nonconverters and incident AD cases. A similar pattern was found in survival analyses; attention and executive function tests, together with tests of learning and recall, significantly predicted incident AD over and above age, gender, and education. CONCLUSION: These results support theoretical models of attention and executive function in the preclinical phase of AD in old age.     

Fine tuning of the digit symbol paired associate recall test for practitioner purposes in clinical and research settings

Guidelines are presented to facilitate the use of the WAIS Digit Symbol measure of paired associate recall as a neuropsychological instrument. Currently three formal variants of the test exist with accompanying normative data (the original WAIS-R-NI form; a WAIS-R Short Form; a longer WAIS-III form), providing a potential source of confusion which may limit its application. To circumvent this, the present article critically evaluates: (i) variations in test forms and their advantages; (ii) available norms in terms of age and education, with pointers for more differentiated guidelines in this regard; and (iii) the desirability of incorporating a delayed recall variant of the test. Finally, a synopsis of data is presented that supports the screening potential of Digit Symbol paired associate recall in cases of mild neurocognitive dysfunction. For the purposes of this paper, the term WAIS is used with broad reference to all variations of the original Wechsler Adult Intelligence Scale (1955) upon which they were based, including the WAIS-R (1981) and WAIS-III (1997) updated editions, and the South African WAIS (1969). The terms South African WAIS (South African Wechsler Adult Intelligence Scale), WAIS-R (Wechsler Adult Intelligence Scale - Revised), and WAIS-III (Wechsler Adult Intelligence Scale-III), refer to these specific versions of the test.     

Neuropsychological Functioning in Depressed Versus Nondepressed Participants with Alzheimer's Disease

Differences in cognitive functioning between participants with Alzheimer's Disease (AD) reporting depressive symptomatology (AD-Dep; n = 37) and a control group of nondepressed participants with AD (AD-Con; n = 98) were investigated based on hypothesized impairments of attention/concentration, psychomotor speed, and simple motor speed. Groups did not differ in age, education, overall severity of dementia, auditory comprehension, or use of psychotropic medications. AD-Dep participants performed significantly more poorly than AD-Con participants on 3 of the 13 measures on which they were hypothesized to exhibit greater impairment (WAIS-R Block Design, WAIS-R Digit Symbol, and speeded motor programming); and there were trends toward poorer performance on four additional measures (WAIS-R Object Assembly, WAIS-R Picture Arrangement, WAIS-R Digit Span-backward, and letter fluency). There was only one significant effect for the 13 measures on which no group differences were hypothesized; the AD-Dep participants unexpectedly obtained better WMS-R Logical Memory delayed recall scores than the AD-Con participants. Finally, AD-Dep participants exhibited an unexpected pattern of greater right hand advantage on the Finger Tapping Test.     

Neuropsychological functioning in depressed versus nondepressed participants with Alzheimer's disease

Differences in cognitive functioning between participants with Alzheimer's Disease (AD) reporting depressive symptomatology (AD-Dep; n = 37) and a control group of nondepressed participants with AD (AD-Con; n = 98) were investigated based on hypothesized impairments of attention/concentration, psychomotor speed, and simple motor speed. Groups did not differ in age, education, overall severity of dementia, auditory comprehension, or use of psychotropic medications. AD-Dep participants performed significantly more poorly than AD-Con participants on 3 of the 13 measures on which they were hypothesized to exhibit greater impairment (WAIS-R Block Design, WAIS-R Digit Symbol, and speeded motor programming); and there were trends toward poorer performance on four additional measures (WAIS-R Object Assembly, WAIS-R Picture Arrangement, WAIS-R Digit Span-backward, and letter fluency). There was only one significant effect for the 13 measures on which no group differences were hypothesized; the AD-Dep participants unexpectedly obtained better WMS-R Logical Memory delayed recall scores than the AD-Con participants. Finally, AD-Dep participants exhibited an unexpected pattern of greater right hand advantage on the Finger Tapping Test.     

A 24-month, double-blind, placebo-controlled multicentre pilot study of the efficacy and safety of nicergoline 60 mg per day in elderly hypertensive patients with leukoaraiosis

In this pilot study, 72 non-demented and non-depressive elderly hypertensive patients with evidence of leukoaraiosis on cerebral computed tomography scan (Rezek score: > 16) were randomly assigned to receive either nicergoline 30 mg b.i.d. (n = 36) or a placebo (n = 36) for 24 months. All patients received antihypertensives and their hypertension was controlled under treatment. They were evaluated by nine neuropsychological tests exploring memory, concentration, verbal and motor performances, administered at baseline and at every six-month interval during the study period. At baseline, the two groups were comparable for all demographic and clinical characteristics, including cognitive functions, except for the delayed recall of the Auditory Verbal Learning Test (AVLT), which was better in the placebo group (P = 0.04). Changes in scores over time were compared between the two groups. At the last visit, patients on nicergoline (n = 31) were found to have deteriorated less or to have improved more on test scores than the patients on placebo (n = 30). Significant differences were observed for memory function (AVLT short term recall, P = 0.026; AVLT delayed recall, P = 0.013; and, Benton Visual Retention Test, P = 0.002) and attention and concentration (Letter Cancellation Test, P = 0.043; and, WAIS-R Digit Symbol subtest, P = 0.006). The Rezek score remained unchanged in the two groups. Tolerance of nicergoline was similar to that of placebo. In conclusion, this study shows that nicergoline 30 mg b.i. d. administered over a 24-month period attenuates the deterioration in cognitive functions in elderly hypertensive patients with leukoaraiosis. Whether these effects were specific for this type of white matter changes could not be determined in the context of this pilot study.     

The subcortical dysfunction hypothesis of memory deficits in depression: neuropsychological validation in a subgroup of patients.

The subcortical dysfunction hypothesis of verbal learning and memory deficits in depression was evaluated by comparing the memory test profiles of unipolar depressives (n = 40) and bipolar depressives (n = 9) with those of patients with a prototypical subcortical dementia (Huntington's disease, HD), patients with a prototypical cortical dementia (Alzheimer's disease, AD), and normal controls. In a discriminant function analysis that well-differentiated the HD, AD, and normal subjects, it was found that 28.6% of the depressed patients were classified as HD patients (DEP-HD subjects), 49.0% were classified as normals (DEP-N subjects), none were classified as AD patients, and 22.4% were not well-classified. The DEP-HD group closely resembled the HD group on additional indices of verbal learning and memory, and differed from the DEP-N group, which strongly resembled the normal control group. DEP-N patients also performed significantly better than DEP-HD patients on a number of other neuropsychological tests (e.g., WAIS-R Digit Symbol, category fluency, Trail Making Test Part B). The findings provide support for the subcortical dysfunction hypothesis, but only for a subgroup of depressed patients. Implications for differentiating depressive "pseudodementia" from AD are discussed.     

Executive and emotional dysfunction in Machado-Joseph disease.

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia. Few studies have examined the neuropsychological and neurobehavioral profiles of patients with MJD. In this study, six individuals with MJD were given a battery of neuropsychological tests. Relative impairments on timed verbal attention tasks and verbal fluency (Stroop, Oral Symbol Digit Modalities, and Controlled Oral Word Association Test) were found. Other executive impairments also were seen on the Wisconsin Card Sorting Test, independent of motor dysfunction severity. Moderate- to severe levels of depressive symptoms were endorsed by four of the six patients, and caregivers observed increased apathy in the patients. Impaired executive and emotional functioning in MJD does not appear to be related to ataxia severity. These patients did not meet the criteria for dementia. General cognitive abilities, language, list learning, story recall, and untimed tasks of attention were within normal limits. Impaired executive abilities and emotional functioning in MJD patients is consistent with disruption of frontal-subcortical systems.     

Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment

CONTEXT: The likelihood of conversion to Alzheimer disease (AD) in mild cognitive impairment (MCI) and the "optimal" early markers of conversion need to be established. OBJECTIVES: To evaluate conversion rates to AD in subtypes of MCI and to identify neuropsychological measures most predictive of the time to conversion. DESIGN: Patients were followed up semiannually and controls annually. Subtypes of MCI were determined by using demographically adjusted regression norms on neuropsychological tests. Survival analysis was used to identify the most predictive neuropsychological measures. SETTING: Memory disorders clinic. PARTICIPANTS: One hundred forty-eight patients reporting memory problems and 63 group-matched controls. MAIN OUTCOME MEASURE: A consensus diagnosis of probable AD. RESULTS: At baseline, 108 patients met criteria for amnestic MCI: 87 had memory plus other cognitive domain deficits and 21 had pure memory deficits. The mean duration of follow-up for the 148 patients was 46.6 +/- 24.6 months. In 3 years, 32 (50.0%) of 64 amnestic-"plus" and 2 (10.0%) of 20 "pure" amnestic patients converted to AD (P = .001). In 148 patients, of 5 a priori predictors, the percent savings from immediate to delayed recall on the Selective Reminding Test and the Wechsler Adult Intelligence Scale-Revised Digit Symbol Test were the strongest predictors of time to conversion. From the entire neuropsychological test battery, a stepwise selection procedure retained 2 measures in the final model: total immediate recall on the Selective Reminding Test (odds ratio per 1-point decrease, 1.10; 95% confidence interval, 1.05-1.14; P < .0001) and Digit Symbol Test coding (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .01). The combined predictive accuracy of these 2 measures for conversion by 3 years was 86%. CONCLUSIONS: Mild cognitively impaired patients with memory plus other cognitive domain deficits, rather than those with pure amnestic MCI, constituted the high-risk group. Deficits in verbal memory and psychomotor speed/executive function abilities strongly predicted conversion to AD.     

Early HIV-related neuropsychological impairment: relationship to stage of viral infection

Sixty male outpatients with no past neuropsychiatric history were examined for evidence of early HIV-related neuropsychological impairment. Significant cognitive deficit, as measured by the RAVLT and WAIS-R Digit Symbol Substitution tests, and moderate correlation with indices of immune function, were observed in a group of patients with AIDS-Related Complex [ARC]. Patients with asymptomatic HIV-infection demonstrated no significant differences in performance compared to a group of HIV-seronegative controls. No significant group differences in age, education, predicted-IQ or self-rated depression and anxiety were observed. These results support the hypothesis that HIV-related cognitive disturbance occurs within the context of immunosuppression.     

Memory and executive function impairment predict dementia in Parkinson's disease.

We analyzed the association of neuropsychological test impairment at baseline with the development of dementia in idiopathic Parkinson's disease (PD) patients. A cohort of nondemented PD patients from northern Manhattan, NY was followed annually with neurological and neuropsychological evaluations. The neuropsychological battery included tests of verbal and nonverbal memory, orientation, visuospatial ability, language, and abstract reasoning. The association of baseline neuropsychological tests scores with incident dementia was analyzed using Cox proportional hazards models. The analysis controlled for age, gender, education, duration of PD, and the total Unified Parkinson's Disease Rating Scale motor score at baseline. Forty-five out of 164 patients (27%) became demented during a mean follow-up of 3.7 +/- 2.3 years. Four neuropsychological test scores were significantly associated with incident dementia in the Cox model: total immediate recall (RR: 0.92, 95% CI: 0.87-0.97, P = 0.001) and delayed recall (RR: 0.73, 95% CI: 0.59-0.91, P = 0.005) of the Selective Reminding Test (SRT), letter fluency (RR: 0.87, 95% CI: 0.77-0.99, P = 0.03), and Identities and Oddities of the Mattis Dementia Rating Scale (RR: 0.85, 95% CI: 0.73-0.98, P = 0.03). When the analysis was performed excluding patients with a clinical dementia rating of 0.5 (questionable dementia) at baseline evaluation, total immediate recall and delayed recall were still predictive of dementia in PD. Our results indicate that impairment in verbal memory and executive function are associated with the development of dementia in patients with PD.     

Prodromal frontal/executive dysfunction predicts incident dementia in Parkinson's disease.

To identify the cognitive characteristics predictive of incident dementia in Parkinson's disease (PD), we examined the baseline neuropsychological profiles of 18 initially non-demented patients with PD who met diagnostic criteria for dementia (PDD) at one-year follow-up. PDD participants' baseline neuropsychological test scores were compared to the baseline performance of 18 patients with PD who did not meet criteria for dementia at one-year follow-up (PDND) and 18 normal controls (NC). The three groups were matched on baseline demographic and disease variables. Relative to the PDND group, the incident PDD participants demonstrated significantly poorer performance on digits backward (Wechsler Memory Scale-Revised), word list learning and recognition (California Verbal Learning Test), and perseverative errors on the Wisconsin Card Sorting Test. Each of these baseline neuropsychological variables exhibited adequate diagnostic classification accuracy in predicting PDD and PDND group membership at follow-up. These results suggest that subtle frontal/executive dysfunction is evident during the immediate PDD prodrome and may be of prognostic value in identifying PD patients at risk for dementia. Accordingly, neuropsychological evaluation may facilitate early identification of PDD and thereby inform appropriate dispositional planning.     

Selective attention and the three-process memory model for the interpretation of verbal free recall in amyotrophic lateral sclerosis

The present study investigates selective attention and verbal free recall in amyotrophic lateral sclerosis (ALS) and examines the contribution of selective attention, encoding, consolidation, and retrieval memory processes to patients' verbal free recall. We examined 22 non-demented patients with sporadic ALS and 22 demographically related controls using Stroop Neuropsychological Screening Test (SNST; selective attention) and Rey Auditory Verbal Learning Test (RAVLT; immediate & delayed verbal free recall). The item-specific deficit approach (ISDA) was applied to RAVLT to evaluate encoding, consolidation, and retrieval difficulties. ALS patients performed worse than controls on SNST (p < .001) and RAVLT immediate and delayed recall (p < .001) and showed deficient encoding (p = .001) and consolidation (p = .002) but not retrieval (p = .405). Hierarchical regression analysis revealed that SNST and ISDA indices accounted for: (a) 91.1% of the variance in RAVLT immediate recall, with encoding (p = .016), consolidation (p < .001), and retrieval (p = .032) significantly contributing to the overall model and the SNST alone accounting for 41.6%; and (b) 85.2% of the variance in RAVLT delayed recall, with consolidation (p < .001) and retrieval (p = .008) significantly contributing to the overall model and the SNST alone accounting for 39.8%. Thus, selective attention, encoding, and consolidation, and to a lesser extent of retrieval, influenced both immediate and delayed verbal free recall. Concluding, selective attention and the memory processes of encoding, consolidation, and retrieval should be considered while interpreting patients' impaired free recall. (JINS, 2012, 18, 1-10).     

The use of neuropsychological tests across Europe: the need for a consensus in the use of assessment tools for dementia

Background and purpose: The centres dedicated to dementia throughout Europe use different neuropsychological tests in clinical practice. The European Federation of Neurological Societies task force on neuropsychological tests produced this survey on neuropsychological tests currently being used in different European countries to gather knowledge on the practice of dementia centres and to promote the harmonization of such instruments and future multicentre collaborations. Methods: National representatives of 34 countries received a questionnaire and 25 (73.5%) sent it back. Results: A few instruments, Mini‐Mental State Examination (MMSE), Trail Making Test (TMT), Verbal Fluency and Clock Drawing Test, were available in all countries. Wechsler Adult Intelligence Scales and MMSE were reported to be valid, respectively, in 20 (80%) and 19 (76%) countries, whereas Verbal Fluency and Stroop Test are valid in 18 (72%) of them. Of the 25 countries, 17 have validation norms for Clock Drawing Test and TMT (68%), and Neuropsychiatric Inventory, Alzheimer’s Disease Assessment Scale – Cognitive Subscale, Rey Complex Figure Test, Digit Symbol and Beck Depression Inventory were standardized in 16 countries (64%). The remaining tests were validated, at most, in about half of them. Not all countries certificate neuropsychology. Conclusions: Despite the substantial differences in the tools used by the EFNS countries for most domains surveyed by the questionnaire, there is at least one neuropsychological instrument used by about 80% of the countries. There is clearly the need for a broader consensus in the use of neuropsychological tests for dementia diagnosis.     

Dementia and effort test performance

Research on the performance of patients with dementia on tests of effort is particularly limited. We examined archival data from 214 non-litigating patients with dementia on 18 effort indices derived from 12 tests (WAIS-III/WAIS-R Digit Span and Vocabulary, Dot Counting Test, Warrington Recognition Memory Test-Words, WMS-III Logical Memory, Rey Word Recognition Memory Test, Finger Tapping, b-Test, Rey 15-Item, Test of Memory Malingering, Rey Auditory Verbal Learning Test, and Rey Complex Figure Test). Results indicated that recommended cut-offs for Digit Span indicators (Vocabulary Minus Digit Span and four-digit forward span time score) provided > or =90% specificity across participants, while the majority of other effort tests displayed specificities in the 30-70% range. Analyses of test specificity as a function of Mini Mental Status Examination (MMSE) score and specific dementia diagnosis are provided, as well as adjustments to cut-offs to maintain specificity where feasible.     

Symbol vs. digit substitution task performance in diverse cultural and linguistic groups

In spite of limited empirical data to guide their use, nonverbal neuropsychological measures are frequently utilized in the assessment of non-native English speakers in an effort to minimize cultural and linguistic factors that may influence performance. In this study, three groups of participants from different cultural and linguistic backgrounds were compared on two brief, nonverbal substitution tasks sensitive to cerebral dysfunction: WAIS-R Digit Symbol and the Symbol Digit Modalities Test. Within each group, participants exhibited a similar pattern of performance, earning higher scores on Digit Symbol. However, when dominant Spanish speakers were further subdivided into higher and lower education groups, less educated Spanish speakers achieved lower scores compared to all other groups on both tasks, and failed to show the performance advantage for Digit Symbol. In spite of differences in the respective countries of educational experience, the more highly educated dominant Spanish speakers performed as well as monolingual nonHispanic and Hispanic bilingual participants on both tasks. Years of formal education appears to be the most relevant variable in explaining performance differences across cultural and linguistic groups on these tasks.     

Auditory P3 indexes personality traits and cognitive function in healthy men and women

The relationship of the auditory P3 event-related potential to major personality dimensions and neuropsychological performance was examined in psychiatrically healthy men and women (28 male, 15 female) recruited from the community. An auditory oddball paradigm was used to collect P3 amplitude and latency data. Personality traits were measured with the NEO Five-Factor Inventory. Several Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtests, the Digit Symbol Test, and the Trail Making Test comprised the neuropsychological tests. A multivariate statistical procedure (Partial Least Squares) was used to quantify the relationships between P3 variables and personality and neuropsychological performance variables. P3 amplitude was negatively related to Neuroticism and positively related to Extraversion, Openness, Agreeableness and Conscientiousness. Better neuropsychological performance was associated with greater P3 amplitude and earlier latency. Thus, greater P3 amplitude was associated with less deviant personality scores and better neuropsychological performance in healthy subjects. Earlier P3 latency was also associated with better neuropsychological performance. The physiological significance of these relationships is not yet clear, but these results suggest that neural assemblies indexed by P3 may subserve both elemental cognition and healthy personality function.     

Cognitive function and frontal lobe atrophy in normal elderly adults: Implications for dementia not as aging-related disorders and the reserve hypothesis

We examined the relations between cognitive function and age and education in the normal elderly population. As per the community-based stroke, dementia, and bed confinement prevention in the town of Tajiri, neuropsychological assessments, including the Cognitive Ability Screening Instrument (CASI), were performed for 99 randomly selected normal elderly subjects. We assessed the frontal function (working memory, word fluency, Trail-Making Tests, CASI subitems of list-generating fluency, attention, and concentration/mental manipulation), language function (proverbs, CASI subitem language), non-language function (the digit symbol test of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), CASI subitem visual construction), memory (Alzheimer's Disease Assessment Scale recall/recognition, story recall, CASI subitems short and long-term memory, the Rey-Osterrieth Complex Figure Test), and the global function (CASI subitems orientation and abstraction and judgment). We found that the only test affected by age was the digit symbol test of the WAIS-R. The effects of education were distributed among various tests. There was a significant correlation between age and the frontal lobe atrophy in the lower educated group. The present findings suggest that cognitive function is spared by the aging process itself and dementia should be considered as age-related, not aging-related disorders, and that education might have a protective effect on cognitive change, supporting the reserve hypothesis.     

Symbol vs. Digit Substitution Task Performance In Diverse Cultural and Linguistic Groups

In spite of limited empirical data to guide their use, nonverbal neuropsychological measures are frequently utilized in the assessment of non-native English speakers in an effort to minimize cultural and linguistic factors that may influence performance. In this study, three groups of participants from different cultural and linguistic backgrounds were compared on two brief, nonverbal substitution tasks sensitive to cerebral dysfunction: WAIS-R Digit Symbol and the Symbol Digit Modalities Test. Within each group, participants exhibited a similar pattern of performance, earning higher scores on Digit Symbol. However, when dominant Spanish speakers were further subdivided into higher and lower education groups, less educated Spanish speakers achieved lower scores compared to all other groups on both tasks, and failed to show the performance advantage for Digit Symbol. In spite of differences in the respective countries of educational experience, the more highly educated dominant Spanish speakers performed as well as monolingual nonHispanic and Hispanic bilingual participants on both tasks. Years of formal education appears to be the most relevant variable in explaining performance differences across cultural and linguistic groups on these tasks.     

Early HIV-related neuropsychological impairment: Relationship to stage of viral infection

Abstract

Sixty male outpatients with no past neuropsychiatric history were examined for evidence of early HIV-related neuropsychological impairment. Significant cognitive deficit, as measured by the RAVLT and WAIS-R Digit Symbol Substitution tests, and moderate correlation with indices of immune function, were observed in a group of patients with AIDS-Related Complex [ARC]. Patients with asymptomatic HIV-infection demonstrated no significant differences in performance compared to a group of HIV-seronegative controls. No significant group differences in age, education, predicted-IQ or self-rated depression and anxiety were observed. These results support the hypothesis that HIV-related cognitive disturbance occurs within the context of immunosuppression.