Valeria Isella

Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease

Apathy is a salient feature of various neuropsychiatric disorders, from depression to Alzheimers disease. We formally assess its prevalence in idiopathic Parkinsons disease (PD) together with its clinical, neuropsychological, and morphometric correlates. Thirty patients with PD and 25 normal controls were assessed using an extensive neuropsychological battery and Marins Apathy Scale; parkinsonian patients also underwent MRI scan, followed by linear measurement of various frontotemporal structures. Approximately 45% of the PD sample showed apathy. For comparison analysis, given the unimodal distribution of the apathy scores, the PD sample was divided into three groups on the basis of the apathy tertiles. All three PD groups had worse cognitive and depression scores than controls, whereas they did not differ in terms of demographic, neurological, general cognitive, or affective features. By contrast, a significant positive association was found between apathy scores and performance on tests of executive function. As regards the morphometric data, we failed to find any specific measure of frontotemporal atrophy correlating with the presence or severity of apathy. Thus, apathy seems to be a frequent and important companion of PD, in many cases probably due to a primary motivational impairment, possibly related to a frontosubcortical dysfunction.

Increased susceptibility to plasma lipid peroxidation in Alzheimer disease patients.

Oxidative stress, linked to Abeta-lipid interactions, plays a pathogenetic role in Alzheimers disease. We investigated modifications of lipid peroxidation products in plasma of 52 AD patients, 42 healthy controls and 16 patients with amyotrophic lateral sclerosis, a neurodegenerative disease where oxidative stress also plays a pathogenetic role. Final lipid peroxidation products were measured in plasma by thiobarbituric acid reactive substances (TBARS) assay before and after ex vivo oxidative stress catalysed by copper. There were no significant changes at basal conditions, but after copper-induced oxidation TBARS levels were higher in AD patients (19.0 microM +/- 2.2) versus both controls (5.2 microM +/- 0.8, p<0.001) and ALS patients (7.6 microM +/- 2.1, p<0.01). Stimulated TBARS levels were significantly higher in mild and moderate AD (p<0.0001) with respect to controls, but not in severe AD patients, with a significant inverse correlation between disease severity and lipid peroxidation (p<0.005, r2=0.21). Treatment of a subgroup (13) of mild and moderate AD patients with vitamin C and E for three months decreased plasma lipoperoxidation susceptibility by 60%. Thus, oxidative stress, expressed as ex vivo susceptibility to lipid peroxidation, appears to be an early phenomenon, probably related to AD pathogenetic mechanisms.

Qualitatively different forms of pure alexia

In this study we investigated two patients with pure alexia, F.C. and L.D.S., in order to make inferences about how processes and levels involved in the early stage of visual word recognition are organized and how they can be selectively damaged. Moreover, we investigated whether pure alexia can be caused by different functional deficits. F.C. and L.D.S. were presented with tasks of letter processing and tasks of orthographic integration. There was a clear double dissociation between the pattern of performance of F.C. and L.D.S. F.C. was able to process single letters rapidly and accurately, but was unable to group together the letters that he had correctly identified. By contrast, L.D.S. was slower and more impaired at letter identification, but she could use letter groups to assist reading. Thus, two different forms of pure alexia emerged: F.C. has a higher level deficit in integrating letters, whereas L.D.S. has a lower level deficit in letter processing. The results support the assumption of a functional organization of the reading process that involves a series of orthographic units (i.e., single letters, sublexical letter groups, and the lexical unit), which can be selectively damaged. Finally, our data present difficulties for models of pure alexia that assume all patients to have a low-level processing deficit.

Screening cognitive decline in dementia: preliminary data on the Italian version of the IQCODE.

Abstract. The IQCODE is a retrospective questionnaire for caregivers about changes which occurred in a patients cognitive and functional efficiency in the previous 10 years of life. Previous studies demonstrated the validity of the IQCODE for the screening of dementia similar to that of traditional cognitive screening tests, with the additional advantage of allowing the detection of cognitive change, rather than just cognitive impairment. The present paper deals with the preliminary results of the validation of the Italian version of the questionnaire in a sample of 45 mild to severely demented patients and 13 patients with mild cognitive impairment (MCI), compared to 20 cognitively intact elderly subjects. The IQCODE demonstrated satisfactory discriminative power for dementia as well as for MCI and a good correlation with the MMSE.

Age-related quantitative and qualitative changes in decision-making ability

The “frontal aging hypothesis” predicts that brain senescence affects predominantly the prefrontal regions. Preliminary evidence has recently been gathered in favour of an age-related change in a typically frontal process, i.e. decision making, using the Iowa Gambling Task (IGT), but overall findings have been conflicting. Following the traditional scoring method, coupled with a qualitative analysis, in the present study we compared IGT performance of 40 young (mean age: 27.9 ± 4.7) and 40 old (mean age: 65.4 ± 8.6) healthy adults and of 18 patients affected by frontal lobe dementia of mild severity (mean age: 65.1 ± 7.4, mean MMSE score: 24.1 ± 3.9). Quantitative findings support the notion that decision making ability declines with age; moreover, it approximates the impairment observed in executive dysfunction due to neurodegeneration. Results of the qualitative analysis did not reach statistical significance for the motivational and learning decision making components considered, but approached significance for the attentional component for elderly versus young normals, suggesting a possible decrease in the ability to maintain sustained attention during complex and prolonged tasks as the putative deficit underlying impaired decision making in normal aging.

Lack of evidence for Borrelia burgdorferi seropositivity in Alzheimer disease.

To the Editor: Borrelia burgdorferi sensu lato (BB) is the etiologic agent of Lyme disease. First identified in 1982, this spirochete is strongly neurotropic, resulting in chronic involvement of the central nervous system. Although defined serologic techniques are available, the diagnosis of neuroborreliosis remains difficult, especially for individuals outside an endemic area or when the typical skin lesions are absent. Interestingly, personality changes and cognitive manifestations may be the first, and occasionally, the only symptoms displayed by the patient. Considering this possibility, several authors examined possible BB involvement in disorders characterized by cognitive impairment, such as Alzheimer disease (AD). Available evidence on the relationship between BB chronic infection and AD is controversial with both positive, and negative results, all deriving from small number of subjects. We, therefore, decided to perform a case-control study, assessing the presence for serum antibodies against BB in 50 mild-to-moderate AD patients [on the basis of the National Institute of Neurological and Communicative Disorder and StrokeAlzheimer’s Disease and Related Disorder Association criteria, with computed tomography/magnetic resonance brain scans and complete neuropsychologic test batteries; age: 75± 7.4 y; disease onset: 71±8y; 22/28 M/F; mini-mental state examination (MMSE) 17.4±5.2; mean±SD]. The patients were recruited from our Dementia Outpatient Unit and compared with 2 groups of age-matched, cognitively-spared controls (MMSE> 26): 25 healthy caregivers of the enrolled patients (age: 72±2.4 y; 15/ 10 M/F), and 23 ‘‘neurologic controls’’ from our Department (age: 71±9y; 0/ 23 M/F; 12 affected by polyneuropathy, 4 by amyotrophic lateral sclerosis, 4 by multiple sclerosis, 1 by myopathy, 1 by myasthenia, and 1 by high-grade glioma). Sera were assayed for BB IgG/IgM antibodies by ELFA (Enzyme Linked Fluorescent Assay; VIDAS Lyme Screen, Biomerieux Italia S.p.A.). The BB antibody index was considered positive when >1.00; borderline when between 0.75 and 1; negative when <0.75. All the assayed sera (both patients and controls) presented an index <0.75 (negative result), with the exception of 1 AD patient that displayed a borderline value (1.00). Thus, our results do not support a role for BB in AD, based on the lack of immune response in an appreciable number of AD subjects. It is, however, known that in both the early and late phases of BB infection the antibody index can be within normal limits, suggesting that the direct measurement of BB antigens in the central nervous system would be more definitive. Moreover, our exploratory case-control study might be underpowered to detect a difference between patients and controls. Although specific data are not available, BB seropositivity in our urban/ suburban region is plausibly very low, so that an extremely high number of subjects would need to be recruited to acquire sufficient power to confirm or refute these preliminary results. Nevertheless, the prevalence estimation calculated based on our results in the AD population is extremely low (2% borderline index), allowing us to suggest that, although a specific role for BB in AD pathogenesis cannot yet be rejected, its putative global impact seems to be almost negligible, arguing strongly against population-based strategies aimed at diagnosis or treatment of this illness for the purpose of ameliorating AD.

Lesions to right prefrontal cortex impair real-world planning through prematurecommitments

While it is well accepted that the left prefrontal cortex plays a critical role in planning and problem-solving tasks, very little is known about the role of the right prefrontal cortex. We addressed this issue by testing five neurological patients with focal lesions to right prefrontal cortex on a real-world travel planning task, and compared their performance with the performance of five neurological patients with focal lesions to left prefrontal cortex, five neurological patients with posterior lesions, and five normal controls. Only patients with lesions to right prefrontal cortex generated substandard solutions compared to normal controls. Examination of the underlying cognitive processes and strategies revealed that patients with lesions to right prefrontal cortex approached the task at an excessively precise, concrete level compared to normal controls, and very early locked themselves into substandard solutions relative to the comparison group. In contrast, the behavior of normal controls was characterized by a judicious interplay of concrete and abstract levels/modes of representations. We suggest that damage to the right prefrontal system impairs the encoding and processing of more abstract and vague representations that facilitate lateral transformations, resulting in premature commitment to precise concrete patterns, and hasty albeit substandard conclusions (because the space of possibilities has not been properly explored).

When Rey-Osterrieth's Complex Figure Becomes a Church: Prevalence and Correlates of Graphic Confabulations in Dementia.

Verbal confabulation (VC) has been described in several pathological conditions characterized by amnesia and has been defined as ‘statements that involve distortion of memories’. Here we describe another kind of confabulation (graphic confabulation, GC), evident at the recall of the Rey-Osterrieth complex figure (ROCF). In a retrospective study of 267 patients with mild-to-moderate dementia, 14 patients (4.9 %) recalled the abstract ROCF as drawings with recognizable semantic meaning. VC was evident at the story recall test in 19.8% of the study participants. VC and GC were homogeneously distributed among the different types of dementia. VC has been proposed to originate from complex interactions of amnesia, motivational deficit and dysfunction of monitoring systems. On the contrary, GC seems to be the result of a deficit in visual memory replaced by the semantic translation of isolated parts of the ROCF along with a source monitoring deficit.

Cognitve estimation: comparison of two tests in nondemented parkinsonian patients

Abstract.The Time and Weight Estimation test (STEP) and the Cognitive Estimation Task (CET) are two recently devised tests for the assessment of cognitive estimation. In the present study, we compared their performance in 30 non-demented idiopathic parkinsonian (PD) patients, also evaluated with the Frontal Assessment Battery (FAB) as an index of executive impairment, with the aim of verifying the putative frontal circuitry of cognitive estimation processes. Six patients (20%) showed a pathological performance on either or both tests. After division of the PD sample into tertiles based on the FAB score, no significant difference was detected by either estimation test. Furthermore, the two questionnaires were unrelated to each other. Thus, deficits of cognitive estimation ability appear to be mild in PD without dementia and do not correlate with executive impairment. Unexpectedly, the CET and the STEP seem to have no unique underlying construct.

Ineffectiveness of an Italian NART-equivalent for the Estimation of Verbal Learning Ability in Normal Elderly

Comparison between current and premorbid memory ability may be of help when trying to make a timely diagnosis of cognitive decline in questionable dementia. In the present study, we evaluated the possibility of estimating episodic verbal memory scores at the Rey Auditory Verbal Learning Test (RAVLT) from an irregular words reading task held to resist to deterioration, that is the Italian analogue of the NART, the TIB (Test d’Intelligenza Breve - brief intelligence test). A regression analysis was performed in a large sample of healthy elderly, using RAVLT scores as dependent variable and TIB score, MMSE score, age and education as predictors. We failed to find a relationship between the two tests that was strong enough for a reliable estimation of memory ability.