Cognitive training in Alzheimer's disease: a controlled randomized study.

This controlled randomized single-blind study evaluated the effects of cognitive training (CT), compared to active music therapy (AMT) and neuroeducation (NE), on initiative in patients with mild to moderate Alzheimer's disease (AD). Secondarily, we explored the effects of CT on episodic memory, mood, and social relationships. Thirty-nine AD patients were randomly assigned to CT, AMT, or NE. Each treatment lasted 3 months. Before, at the end, and 3 months after treatment, neuropsychological tests and self-rated scales assessed initiative, episodic memory, depression, anxiety, and social relationships. At the end of the CT, initiative significantly improved, whereas, at the end of AMT and NE, it was unchanged. Episodic memory showed no changes at the end of CT or AMT and a worsening after NE. The rates of the patients with clinically significant improvement of initiative were greater after CT (about 62%) than after AMT (about 8%) or NE (none). At the 3-month follow-up, initiative and episodic memory declined in all patients. Mood and social relationships improved in the three groups, with greater changes after AMT or NE. In patients with mild to moderate AD, CT can improve initiative and stabilize memory, while the non-cognitive treatments can ameliorate the psychosocial aspects. The combining of CT and non-cognitive treatments may have useful clinical implications.

The course of language functions after temporal lobe epilepsy surgery: a prospective study.

BACKGROUND AND PURPOSE: Anterior temporal lobectomy (ATL) within the language-dominant hemisphere can impair naming. This prospective study examined the pre-operative to post-operative course of different language components, clarifying which changes are relevant within the short-term and long-term outcome of language. METHODS: Patients with drug-resistant temporal lobe epilepsy (TLE) were evaluated using the Token, Boston Naming and Word Fluency tests assessing sentence comprehension and word-finding on visual, semantic or phonemic cues. RESULTS: A total of 106 patients were evaluated before and 6 months, 1 and 2 years after ATL; 60 patients were also evaluated after 5 years and 38 controls were assessed at baseline. Seizure outcome was comparable between the left and right TLE patients. Before surgery, naming and word fluency were impaired in the left and right TLE patients, whereas sentence comprehension was normal. After left or right ATL, word fluency progressively improved, naming showed early worsening and late improvement after left ATL and progressive improvement after right ATL, and sentence comprehension did not change. At the 5-year follow-up, naming improvement was clinically significant in 31% and 71% of the left and right TLE patients, respectively. Pre-operative naming, ATL laterality, schooling, and post-operative seizure frequency and number of antiepileptic drugs predicted post-operative naming. Pre-operative word fluency and schooling predicted post-operative word fluency. CONCLUSIONS: Left or right TLE can impair word-finding but not sentence comprehension. After ATL, word-finding may improve for a long time, depending on TLE laterality, seizure control and mental reserve. These findings may clarify prognosis prior to treatment.

Preoperative language lateralization in temporal lobe epilepsy (TLE) predicts peri-ictal, pre- and post-operative language performance: An fMRI study.

In patients with temporal lobe epilepsy (TLE), assessment of language lateralization is important as anterior temporal lobectomy may lead to language impairments. Despite the widespread use of fMRI, evidence of its usefulness in predicting postsurgical language performance is scant. We investigated whether preoperative functional lateralization is related to the preoperative language performance, peri-ictal aphasia, and can predict language outcome one year post-surgery. We studied a total of 72 TLE patients (42 left, 30 right), by using three fMRI tasks: Naming, Verb Generation and Fluency. Functional lateralization indices were analyzed with neuropsychological scores and presence of peri-ictal aphasia. The key findings are:1)Both left and right TLE patients show decreased left lateralization compared to controls.2)Lateralization correlates with language performance before surgery. In left TLE, decreased left lateralization correlates with better fluency performance. In right TLE, increased left lateralization during the Naming task correlates with better naming.3)Left lateralization correlates with peri-ictal aphasia in left TLE patients.4)Lateralization correlates with language performance after surgery. In a subgroup of left TLE who underwent surgery (17 left), decreased left lateralization is predictive of better naming performance at 6 and 12 months after surgery. The present study highlights the clinical relevance of fMRI language lateralization in TLE, especially to predict language outcome one year post-surgery. We also underline the importance of using fMRI tasks eliciting frontal and anterior temporal activations, when studying left and right TLE patients.

Music, music therapy and dementia: a review of literature and the recommendations of the Italian Psychogeriatric Association.

This study reviews the most recent (from 2000 to 2011) Clinical Controlled Trials (CCT) and Randomized Controlled Trials (RCT) concerning the use of music and music-therapy (MT) in the context of dementia and related issues. Studies which explored the efficacy of music and MT on behavioral and psychological symptoms of dementia (BPSD) are prevalent, while those aiming at assessing a potential effect of these approaches on cognitive and physiological aspects are scant. Although with some limitations, the results of these studies are consistent with the efficacy of MT approach on BPSD. In this context, the ability of the music therapist to directly interact with the patients appears to be crucial for the success of the intervention. This review was endorsed by the Italian Psychogeriatric Association (AIP) and represents its view about the criteria to select appropriate music and MT approaches in the field of dementia. Accordingly, we have developed a list of recommendations to facilitate the current use of these techniques in the context of non-pharmacological treatments for patients with dementia.

Cognitive abilities of musicians.

Playing music may involve different cognitive domains, but previous studies of musicians and patients with brain lesions have reported inconsistent associations between music performances and other cognitive functions. Fine musical performance may be associated with high executive and control functions. 21 skilled musicians and 21 age- and education-matched healthy controls with no specific musical competence were compared on attentive, executive, linguistic, perceptual, praxic, memory, and theory of mind functions, using standardized neuropsychological tests. No differences between the musicians and controls, music composers and performers, or between soloists or orchestral players were observed. In musicians, there was no correlation between the test scores and amount of music education. Findings based on these musician groups, carefully evaluated, suggest further exploration of associations of distinct components of music comprehension and expression with different cognitive functions and behavioral aspects.

Preserved memory in temporal lobe epilepsy patients after surgery for low-grade tumour. A pilot study.

The objective was to carry out a pilot study exploring memory outcome in patients with temporal lobe epilepsy (TLE) and low-grade tumour. A prospective study using a competence-related memory assessment was carried out in the Laboratory of Neuropsychology, Epilepsy Center and Neurosurgical Department of the "C. Besta" National Neurological Institute in 24 TLE patients undergoing surgical resection for left (n=12) or right (n=12) low-grade tumours and 36 healthy subjects. Patients underwent mesial or lateral temporal lobe lesionectomy. Neuropsychological tests exploring verbal and visual short-term memory, learning, delayed recall and ability to control interference in memory were applied. Before and after surgery, significant verbal impairment was present in left TLE patients compared to controls and right TLE patients, and visual deficits were present in both groups compared to controls. After surgery, there was no significant decrease in mean verbal or visual memory scores related to the operated side. Some memory abilities subserved by the contralateral temporal lobe improved. Postoperative memory scores were related to preoperative scores, side of operation, age and education. In patients with TLE and low-grade tumour, temporal lobe surgery does not necessarily induce memory deficits. Improvement of memory abilities subserved by the unoperated temporal lobe may be expected.

Methotrexate based chemotherapy and deferred radiotherapy for primary central nervous system lymphoma (PCNSL): single institution experience.

In the following study, we present our experience in the treatment of PCNSL patients using a multi-step schedule combining chemotherapy and deferred radiotherapy. Patients were treated with two modified M-BACOD cycles and then differently according to radiological response For PR, SD and PD patients, chemotherapy was interrupted and radiotherapy initiated immediately (45 Gy Whole-brain RT). With CR patients, chemotherapy was continued with a combination of HMTX, VCZ, PCB and HD Ara-C up to a total of nine cycles. In 36 patients suitable for evaluation (2 patients had undergone tumour resection): 69.4% (25 of 36) had a complete response (CR), 19.4% (7 of 36) had a partial response(PR), 8.3% (3 of 36) had stable disease(SD), and 2.7% (one of 36) had progressive disease (PD). The PR, SD and PD patients were immediately treated by radiotherapy. In this cohort of patients, we observed 6 CR, 4 PR and 2 PD, respectively, following radiotherapy. At first relapse, a total of 16 CR patients were treated by radiotherapy for a total dose of 45 Gy. The OS was 42.1 months for the entire group of patients. In CR patients treated at the moment of recurrence by salvage radiotherapy, the TTP (time lasting from histological diagnosis until recurrence of disease before RT) was 28.3 months, with a 43.4% of disease free patients observed at 2 years. The median disease-free time observed after complete response to radiotherapy was 10.5 months. In 16 patients (34%), further progression of disease was observed following radiotherapy. Two patients developed extra-CNS disease in the breast and testis. When taking into account the patients with radiotherapy delayed at recurrence, the OS was 48 months and the survival rates were 70% and 60% at 2 years and 5 years, respectively.

Facets and determinants of quality of life in patients with recurrent high grade glioma.

OBJECTIVES: To assess patients with recurrent high grade brain glioma with the aim of evaluating facets of quality of life (QOL) and their association with mood, cognition, and physical performance. METHODS: Ninety four glioma patients (four groups with different duration of glioma recurrence) were compared with 24 patients with other chronic neurological diseases and 48 healthy subjects. The Functional Living Index-Cancer (FLIC) provided QOL self evaluations, and standardised scales and neuropsychological tests assessed physical performance, mood, and cognition. RESULTS: In glioma patients, factor analysis of the FLIC items documented five domains: Psychological well being, Role/sociability, Inner experience of disease, Isolation/sharing, and Nausea. Higher FLIC total scores were related to better cognition, physical performances, and mood, and lower grading; poorer Psychological well being and worse Inner experience of disease to depressed mood; minor Role/sociability to worse cognitive and physical performances and higher grading; worse Nausea to longer disease duration. Compared with healthy subjects, all glioma groups were cognitively impaired and more anxious, and two groups with short duration of recurrence were also more depressed. Patients with chronic neurological diseases showed worse mood and cognitive abilities compared with healthy subjects, but performed attention tests better than glioma patients. Glioma and chronic disease patients showed similar FLIC scores and autonomy. CONCLUSIONS: These results show that QOL of recurrent high grade glioma patients is multifaceted and determined by multiple factors. Disease severity does not necessarily eliminate the possibility of expressing personal feelings and opinions which could provide criteria for clinical decision making and psychological support.

A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene.

Three members of an Italian family with autosomal dominant dementia and multiple strokes had the A713T mutation of the APP gene. The neuropathologic examination of the proband disclosed Alzheimer disease (AD) with severe cerebral amyloid angiopathy and multiple infarcts. This indicates that the A713T mutation of the APP gene, lying at the gamma-secretase cleavage site, can be responsible for AD with symptomatic cerebral amyloid angiopathy.

Relation of sorting impairment to hippocampal damage in temporal lobe epilepsy.

One hundred and twelve patients with left (n=65) or right (n=47) temporal lobe epilepsy (TLE), associated with mesial or lateral temporal lobe lesion, were compared to 53 patients with left (n=30) or right (n=23) frontal lobe epilepsy (FLE), in order to explore the contributions of hippocampal lesions and of memory deficits to sorting impairment. Thirty-six healthy subjects of similar age and education were controls. The Modified Wisconsin Card Sorting Test (MWCST) was used to explore sorting ability. The two-syllable word span and consistent long-term retrieval from the selective reminding procedure for word-list learning were used to evaluate memory. Raven's Coloured Progressive Matrices and Attentive Matrices served to control for abstract reasoning and attention. Left FLE patients and TLE patients with left hippocampal sclerosis were significantly impaired on MWCST, short-term memory, and word learning. TLE patients with other left hippocampal lesions were also impaired on MWCST, although not significantly so. Analysis of individual scores showed that 42% of TLE patients with left hippocampal sclerosis, 14% of TLE patients with other hippocampal lesions, 63% of left FLE patients, and 30% of right FLE patients were impaired on the MWCST. In patients with left hippocampal sclerosis, MWCST score was associated with the learning score provided by the selective reminding procedure and Raven's Coloured Progressive Matrices score, whereas in FLE patients, MWCST score was associated with Attentive Matrices score. These results suggest that only some TLE patients, i.e. those with hippocampal damage, may be expected to be impaired on card sorting. The impaired sorting ability of these TLE patients may be due to involvement of the hippocampal function in forming associations or in registering new information.

Positive response to immunomodulatory therapy in an adult patient with Rasmussen's encephalitis.

Rasmussen's encephalitis (RE) is a rare and progressive neurologic condition of uncertain etiology that typically has a childhood onset. The authors describe a 45-year-old woman with adult-onset progressive aphasia, right hemiparesis, severe drug refractory epilepsy, and left cerebral hemisphere atrophy. High-dose corticosteroids and plasmapheresis were not effective. She improved with high-dose therapy with human IV immunoglobulin.

Preserved semantic access in global amnesia and hippocampal damage.

C.B., a right-handed 33-year-old man, presented with anterograde amnesia after acute heart block. Cognitive abilities were normal except for serious impairment of long-term episodic memory. The access to semantic information was fully preserved. Magnetic resonance showed high signal intensity and marked volume loss in the hippocampus bilaterally; the left and right parahippocampal gyrus, lateral occipito-temporal gyrus, inferior temporal gyrus, and lateral temporal cortex were normal. This case underlines that global amnesia associated with hippocampal damage does not affect semantic memory. Although the hippocampus is important in retrieving context-linked information, its role is not so crucial in retrieving semantic contents. Cortical areas surrounding the hippocampus and lateral temporal areas might guide the recall of semantic information.

Quality of life and memory performance in patients with temporal lobe epilepsy.

OBJECTIVE: To explore the contribution of memory performance to quality of life (QOL) in patients with left or right temporal lobe epilepsy (TLE). SUBJECTS AND METHODS: Sixty-five patients with left or right TLE compiled the QOL in Epilepsy-89 Inventory (QOLIE-89), the State-Trait Anxiety Inventory (STAI) and the Hopelessness Scale (BDI) for self-evaluation of QOL and mood. Memory was assessed by tests of verbal and non-verbal memory and the Questionnaire of Memory Efficiency (QME). A neuropsychological battery was also administered to assess general intelligence, attention, visual perception, language, set shifting, word fluency and conceptual-motor tracking. RESULTS: On factor analysis, the neuropsychological battery and mood scales consisted of six factors (Memory, Mental Speed, Mood, Praxis, Sorting and Perception), while the QOLIE-89 consisted of five factors (Psychosocial Satisfaction, Epilepsy-Related Effects, Role, Physical Performance, Cognition). On regression analysis, overall QOLIE-89 score was predicted by the factor Mood and QME score. The QOLIE-89 factor Cognition was predicted by QME score and the Memory, Mental Speed, Perception and Praxis factors of the neuropsychological battery. CONCLUSION: In TLE patients self-reported memory, as assessed by QME, is an important predictor of QOL, and also correlates with performance on memory tests. This suggests that memory improvement by specific training may help to improve QOL in these patients.

Verbal semantic memory in temporal lobe epilepsy.

OBJECTIVES: Temporal lobe epilepsy (TLE) may determine memory difficulties not explained by episodic memory impairment. The present study was aimed to verify the presence of specific semantic memory dysfunctions in TLE and to explore their relations to epilepsy variables. SUBJECTS AND METHODS: Forty-seven patients with lateralized temporal (n = 26) or extra-temporal lobe epilepsy (n = 21) and 23 healthy subjects were compared. Picture Naming and Pointing to a Picture were used to explore expressive and receptive vocabulary and the Semantic Questionnaire evaluated semantic judgment of verbally presented items. The Selective Reminding Procedure for word list learning and Story Recall were used to assess episodic memory. Spontaneous speech and the Token Test controlled for language disturbances, and Raven's Coloured Progressive Matrices were used to evaluate abstract reasoning ability. RESULTS: Multivariate analysis of variance of test scores showed significant impairment of semantic memory in patients with left TLE compared to healthy controls, whereas episodic memory was impaired in left temporal and extra-temporal epilepsy (as measured by word learning) and all epilepsy groups (as measured by Story Recall). In the TLE groups, naming abilities were more compromised than single-word comprehension and semantic judgment - which were not significantly affected. No deficits in language abilities or in abstract reasoning were found in any patient group. Factor analysis of memory tests scores in the patients produced two factors, one semantic and the other episodic. Regression analysis revealed that the semantic factor was related to abstract reasoning, left hemisphere lateralization of seizures, and age of seizure onset; while the episodic factor was related to age. CONCLUSIONS: Left TLE may determine significant verbal semantic memory compromise, maybe due to impaired access to the semantic-lexical storage. In non-aphasic epilepsy patients, comparison of performance on semantic and episodic memory tests may be useful for assessing the nature of memory failures, and may complement clinical and neurophysiological means for defining the epileptic center.

Quality of life in patients with stable disease after surgery, radiotherapy, and chemotherapy for malignant brain tumour.

OBJECTIVES: to evaluate quality of life in patients with malignant brain tumour with stable disease after combined treatments in comparison to patients with other chronic neurological conditions, and to explore the relation of quality of life to clinical, pathological, affective and cognitive factors. METHODS: fifty seven patients who were stable after surgery, radiotherapy and chemotherapy and 24 controls with spastic paraparesis, peripheral neuropathies, myasthenia, ataxia, Parkinson's disease, or multiple sclerosis, were studied. Patients were evaluated by functional living index-cancer, Karnofsky performance status, activity of daily living, self-rating depression scale, state-trait anxiety inventory, and tests for cognitive abilities. RESULTS: separate Mann-Whitney test comparisons did not show any difference in measures of health related quality of life (functional living index-cancer), autonomy in daily life (activity of daily living), or mood between tumour and control patients, although the first had slower mental speed and worse attention. Seventy three per cent of patients with brain tumour and 58% of the control patients continued or resumed previous work activity. Quality of life was significantly associated with depression, state anxiety, and performance status in the patients with brain tumour, whereas in control patients, state anxiety was the only factor related to quality of life. CONCLUSIONS: after intensive multimodality treatments, selected patients with brain tumour with stable disease may have satisfactory quality of life that may be not worse than in patients with other chronic neurological illnesses. During the period of stable disease, depressed mood, possibly a reaction to impaired physical and cognitive performance, seems to play a major role in determining quality of life.

Learning and memory impairment in patients with temporal lobe epilepsy: relation to the presence, type, and location of brain lesion.

PURPOSE: To study the influence of epileptogenic lesions on learning and memory alterations in patients with temporal lobe epilepsy (TLE). METHODS: We studied 131 patients (55 with left and 39 with right lesional TLE; 22 with left and 15 with right cryptogenic TLE) and 36 healthy subjects. We compared these groups by using a battery of tests to assess verbal and visual learning, delayed recall, and recall after the imposition of interfering activity. RESULTS: Compared with the controls and patients with right TLE, the patients with left TLE were significantly impaired on all verbal tests. On visual tests, patients with right TLE were impaired compared with controls but not more so than patients with left TLE. Separate multivariate analyses of variance (MA-NOVAs) of patients' verbal and visual test scores, taking the TLE side and morphologic features of the temporal lobes (i.e., normal, hippocampal sclerosis, low-grade glioma, or cavernous angioma) as independent factors, did not show any significant effect of these features. Separate comparisons of verbal and visual test scores of patients with lesional TLE, taking the side and location (mesial or lateral) of the epileptogenic lesion as independent factors, did not show any significant effect of location. CONCLUSIONS: Our findings show that some learning and memory abilities are impaired in patients with TLE irrespective of the presence of overt damage. This supports the theory that focal epileptic discharges, rather than the lesions themselves, affect these functions. The pathologic characteristics and intratemporal location of an associated lesion do not seem to play an important role in determining learning and memory impairment when clinical and treatment-related factors are taken into account.