Hana Markova

Neuropsychological correlates of hippocampal atrophy in memory testing in nondemented older adults.

BACKGROUND AND OBJECTIVE Cognitive deficits in older adults attributable to Alzheimers disease (AD) pathology are featured early on by hippocampal impairment. Among tests used to evaluate memory, verbal memory tests with controlled encoding and cued recall are believed to be specific for hippocampal impairment. The objective of this study was to assess the relation between left and right hippocampal volumes and several frequently used memory tests. METHODS Fifty six nondemented older adults (30 with amnestic mild cognitive impairment and 26 cognitively healthy older adults) underwent neuropsychological testing including: (1) The Enhanced Cued Recall test (ECR), a memory test with controlled encoding and recall; (2) the Auditory Verbal Learning Test (AVLT), a verbal memory test without controlled encoding and with delayed recall; and (3) The Rey-Osterrieth Complex Figure test (ROCF), a visuospatial memory test-recall condition. 1.5T brain MRI scans were used to measure estimated total intracranial volume (eTIV) along with hippocampal right and left volumes, which were measured with quantitative volumetry using FreeSurfer package (version 4.4.0). Spearman partial correlation controlled for age was used to correct for non-normal score distribution and effect of age. RESULTS We found moderate correlations of hippocampal volumes with AVLT 1-5 scores, AVLT delayed recall, ECR free and total recall, and ROCF reproduction. Total recall in ECR using cued recall was not superior to any of the free recall tests. No correlation in any memory test was achieved with eTIV. CONCLUSION Verbal memory tests, either with controlled encoding and cued delayed recall (ECR), or without it (AVLT), as well as nonverbal memory test with delayed recall (ROCF), equally reflect hippocampal atrophy in nondemented older adults.

Subjective Cognitive Complaints in Cognitively Healthy Older Adults and Their Relationship to Cognitive Performance and Depressive Symptoms

BACKGROUND Subjective cognitive complaints (SCCs) may be an early marker of prodromal Alzheimers disease. OBJECTIVES Using a 10-item yes/no SCCs questionnaire (Le Questionnaire de Plainte Cognitive [QPC]), we evaluated the prevalence and distribution of SCCs in cognitively healthy Czech older adults and examined total score and specific QPC items in relation to depressive symptomology and cognitive performance. METHODS A sample of 340 cognitively healthy older community-dwelling volunteers aged 60 or older from the third wave of the longitudinal project National Normative Study of Cognitive Determinants of Healthy Aging, who underwent a comprehensive neuropsychological assessment and completed the QPC and the 15-item Geriatric Depression Scale (GDS-15). Regression analysis was controlled for age when GDS-15 was the outcome and for age and GDS-15 with cognitive domains as the outcome. RESULTS 71% reported 1 + SCCs, with prevalence of individual complaints ranging from 4% to 40%. The number of SCCs was associated with GDS-15 (p < 0.001). Personality change (p < 0.001) and Limitation in daily activities (p = 0.002) were significantly associated with higher GDS-15 score and Spatial orientation difficulties (p = 0.019) and Impression of worse memory in comparison to peers (p = 0.012) were significantly associated with lower memory performance. CONCLUSIONS We identified some cognitive complaints that were very common in our sample. Overall, a higher number of SCCs in well cognitively functioning individuals was most closely related to depressive symptomatology, while some specific complaints reflected lower memory performance and should be considered when screening for people at risk of cognitive decline.

Clock Drawing Test and the diagnosis of amnestic mild cognitive impairment: Can more detailed scoring systems do the work?

Introduction: The Clock Drawing Test is a frequently used cognitive screening test with several scoring systems in elderly populations. We compare simple and complex scoring systems and evaluate the usefulness of the combination of the Clock Drawing Test with the Mini-Mental State Examination to detect patients with mild cognitive impairment. Method: Patients with amnestic mild cognitive impairment (n = 48) and age- and education-matched controls (n = 48) underwent neuropsychological examinations, including the Clock Drawing Test and the Mini-Mental State Examination. Clock drawings were scored by three blinded raters using one simple (6-point scale) and two complex (17- and 18-point scales) systems. The sensitivity and specificity of these scoring systems used alone and in combination with the Mini-Mental State Examination were determined. Results: Complex scoring systems, but not the simple scoring system, were significant predictors of the amnestic mild cognitive impairment diagnosis in logistic regression analysis. At equal levels of sensitivity (87.5%), the Mini-Mental State Examination showed higher specificity (31.3%, compared with 12.5% for the 17-point Clock Drawing Test scoring scale). The combination of Clock Drawing Test and Mini-Mental State Examination scores increased the area under the curve (0.72; p < .001) and increased specificity (43.8%), but did not increase sensitivity, which remained high (85.4%). Conclusions: A simple 6-point scoring system for the Clock Drawing Test did not differentiate between healthy elderly and patients with amnestic mild cognitive impairment in our sample. Complex scoring systems were slightly more efficient, yet still were characterized by high rates of false-positive results. We found psychometric improvement using combined scores from the Mini-Mental State Examination and the Clock Drawing Test when complex scoring systems were used. The results of this study support the benefit of using combined scores from simple methods.

Mastoiditis complicated with Gradenigo syndrome and a hypertrophic pachymeningitis with consequent communicating hydrocephalus

We present the clinical, radiological and pathological features of a case of a cranial hypertrophic pachymeningitis that developed in the course of mastoiditis and petrous apex inflammation and responded to immunosuppressive therapy only. Documented by the development of clinical findings, magnetic resonance imaging, cerebrospinal fluid changes, histopathology findings, by otosurgical intervention and finally by the insertion of a ventriculo-peritoneal shunt, the case illustrates a gradual development of pachymeningitis with consequent hydrocephalus and intracranial hypertension. We consider this disease development an example of immune-induced proliferative fibrotic changes in meninges.

Homocysteine and Real-Space Navigation Performance among Non-Demented Older Adults

BACKGROUND High plasma homocysteine (Hcy) level is related to higher risk of Alzheimers disease (AD) and lower cognitive performance in older adults. OBJECTIVE To assess the association between plasma Hcy level and real-space navigation performance and the role of vascular risk and protective factors, APOE status, and white matter lesions (WML) on this association. METHODS Ninety-two non-demented older adults (29 with amnestic mild cognitive impairment, 46 with subjective cognitive decline, and 17 cognitively normal older adults) underwent spatial navigation testing of egocentric, allocentric, and mixed navigation in a real-space analogue of the Morris water maze, neuropsychological examination, blood collection, and MRI brain scan with evaluation of WML. RESULTS In the regression analyses controlling for age, gender, education, and depressive symptoms, higher plasma Hcy level was related to worse mixed and egocentric (β= 0.31; p = 0.003 and β= 0.23; p = 0.017) but not allocentric (p > 0.05) navigation performance. Additional controlling for vascular risk and protective factors, WML, and APOE status did not modify the results. High total cholesterol and low vitamin B12 and folate levels increased the adverse effect of Hcy on egocentric and mixed navigation. WML did not explain the association between plasma Hcy level and navigation performance. CONCLUSION Elevated plasma Hcy level may affect real-space navigation performance above and beyond vascular brain changes. This association may be magnified in the presence of high total cholesterol and low folate or vitamin B12 levels. Attention to the level of plasma Hcy may be a viable intervention strategy to prevent decline in spatial navigation in non-demented older adults.

Perspective taking abilities in amnestic mild cognitive impairment and Alzheimer's disease

Perspective taking is the ability to imagine what a scene looks like from a different viewpoint, which has been reported to be impaired in Alzheimers disease (AD). This study compared overhead and first-person view perspective taking abilities in patients with mild cognitive impairment (MCI) and AD. A newly developed Arena Perspective Taking Task (APTT), using an environment of a circular arena, was used to compare 23 AD patients and 38 amnestic MCI patients with 18 healthy controls. The results were contrasted with a published perspective taking test (Standardized Road-Map Test of Direction Sense, RMTDS). The AD group was impaired in both overhead and first-person view APTT versions, but the impairment in the overhead view version applied specifically to women. Patients with aMCI were impaired in the first-person view but not in the overhead view version. Substantial sexual differences were found in the overhead but not in the first-person view APTT version. The RMTDS resembled both APTT versions: patients with aMCI were impaired in this test and also women in both patient groups were less accurate than men. Using the receiver operating characteristic analysis, the highest predictive power for MCI and AD patients diagnosis versus controls was observed for their success rate in the first-person view version. The results suggest distinction between overhead and first-person view perspective taking in the impairment of aMCI patients and the sex differences. The first-person view perspective taking is a potentially important candidate psychological marker for AD.

Clock drawing test in screening for Alzheimer's dementia and mild cognitive impairment in clinical practice.

The clock drawing test (CDT) is a commonly used brief cognitive measure. We evaluated diagnostic accuracy of subjective ratings of CDT by physicians (with/without specialty in cognitive neurology) and neuropsychologists in discriminating amnestic mild cognitive impairment (aMCI), Alzheimers dementia (AD) and cognitively healthy older adults. We further compared the diagnostic accuracy of subjective categorical ratings with complex scoring of CDT.

Semantic verbal fluency impairment is detectable in patients with subjective cognitive decline

ABSTRACT Patients with subjective cognitive decline (SCD) are at higher risk for conversion to dementia due to Alzheimer’s disease (AD). Semantic verbal fluency (SVF) seems to be impaired in the early stages of AD. The goal of the present study was to identify the discriminative potential of verbal fluency (VF) in patients with SCD to show if very early signs of cognitive decline may be detected in SCD. We examined 93 normal controls (NC) and 61 participants with SCD. Each participant was administered a comprehensive neuropsychological battery. All participants underwent tests of VF: phonemic verbal fluency (PVF), letters K and P and SVF (animals and vegetables categories). In addition to the total score, two 30-second intervals, and clustering and switching indices in SVF were evaluated. SCD generated fewer words in the total score and 30- to 60-second interval in vegetables category and they performed more switches in animals category. There was no significant difference between the SCD and the NC groups in all other VF measures. Quantitative measures of SVF (a decreased number of vegetables) as well as qualitative measures were detected in SCD group and could be considered as an early neuropsychological marker of subtle cognitive impairment.

The effect of TOMM40 on spatial navigation in amnestic mild cognitive impairment

Background:We developed the Audio Recorded Cognitive Screen (ARCS) to facilitate efficient cognitve testing with minimal time demands on the clinician. The ARCS tests five cognitive domains using an audio device. Patients are unsupervised throughout the testing and respond to the questions on the audio by writing their responses in a special booklet for later scoring. On completion, patients record their socio-demographic details and complete multiple choice questions at the back of the response booklet. Questions include: Do you have problems with your memory (yes/no)? How well do you think you performed on the test of memory and concentration? Could you hear the instructions on the recording clearly? Did you find the directions on the recording confusing or difficult to follow? Here we explore the relationship between responses to these questions and age, gender, educational attainment, and actual performance on the ARCS. Methods: The ARCS was administered to outpatientson clinical grounds and in the absence of contraindications such as illiteracy, inability to write because of motor or other problems or profound hearing deficit. Testing was conducted in a quiet room, unsupervised. Scoring was undertaken by trained scorers who entered raw scores into an excel ’calculator’ program for computation of demographically-scaled scores. The responses to the questions above were grouped into categories and associations were sought using chi-square, t-tests and multivariate statistical techniques. Results:We analysed data from 539 individuals (58% male), aged 15-88 yr (mean 52.6 yr), 40% with 10 years education or less. Eighty-three percent reported memory problems, 26% thought they had done very well (6%) or quite well (20%) on the test, 96% reported no difficulty hearing the instructions, and 87% reported that they understood the instructions clearly, while 8% ’sometimes’ had difficulty and 3% had difficulty understanding the instructions ’most of the time’. Reports of difficulty hearing or understanding the instructions and lower self-rated performance (but not memory complaints) were associated with poorer performance on testing. Conclusions: Additional caution in the interpretation of ARCS scores should be taken when patients report having difficulty hearing or understanding the instructions provided.

Spatial navigation deficits in amnestic mild cognitive impairment with neuropsychiatric comorbidity

ABSTRACT Aims: To find out whether neuropsychiatric comorbidity (comMCI) influences spatial navigation performance in amnestic mild cognitive impairment (aMCI). Methods: We recruited aMCI patients with (n = 21) and without (n = 21) neuropsychiatric comorbidity or alcohol abuse, matched for global cognitive impairment and cognitively healthy elderly participants (HE, n = 22). They completed the Mini-Mental State Examination and a virtual Hidden Goal Task in egocentric, allocentric, and delayed recall subtests. Results: In allocentric navigation, aMCI and comMCI performed significantly worse than HE and similarly to each other. Although aMCI performed significantly worse at egocentric navigation than HE, they performed significantly better than patients with comMCI. Conclusions: Despite the growing burden of dementia and the prevalence of neuropsychiatric symptoms in the elderly population, comMCI remains under-studied. Since trials often assess “pure” aMCI, we may underestimate patients’ navigation and other deficits. This finding emphasizes the importance of taking account of the cognitive effects of psychiatric disorders in aMCI.