Cognitive effects of low-dose topiramate monotherapy in epilepsy patients: A 1-year follow-up

The present study was conducted to evaluate the long-term effects of low-dose topiramate (TPM) monotherapy on the cognitive function of epilepsy patients. Forty-seven epilepsy patients received TPM, with target doses of 50, 75, and 100 mg/day. Cognitive tests were performed twice, at baseline and 1 year after starting medication. Thirty-six patients completed the follow-up neuropsychological tests. After a year of treatment, 16 patients (44%) complained of cognitive problems. Although it improved seizure frequency and EEG abnormalities, TPM had significantly negative effects on the digit span and verbal fluency tests. These cognitive effects were dose-related and significantly improved after withdrawal from TPM and substitution with older antiepileptic drugs. In conclusion, even at a low dose, TPM has long-term, negative effects on working memory and verbal fluency.     

Sub-threshold cognitive impairment in multiple sclerosis: the association with cognitive reserve

Multiple sclerosis (MS) patients with high premorbid intellect have the advantage of cognitive reserve that may mitigate the effects of cognitive decline. A fall-off in cognition may nevertheless still occur, even should it fail to meet global impairment thresholds. The present cross-sectional study explores the neurologic and behavioral characteristics of this little known group of patients. A consecutive sample of 144 MS patients underwent neuropsychological testing with the minimal assessment of cognitive function in the MS (MACFIMS) battery. Premorbid IQ was assessed with the ANART reading test. A validated algorithm based on ANART errors and verbal fluency scores was used to predict whether current cognitive function matched premorbid estimates. Three MS groups were thus defined: cognitively intact (n = 53), impaired (n = 46) and cognitively intact on the MACFIMS, but falling short of premorbid predictions (n = 45). Patients who were cognitively intact on the MACFIMS but fell short of verbal fluency predictions had higher premorbid IQ (p = 0.007) and lower EDSS (p = 0.002) than cognitively impaired, but not intact patients. They outperformed impaired patients on every MACFIMS variable, but were more impaired than intact patients on the Paced Auditory Serial Addition Test-3 (PASAT-3) (p = 0.009). They were more likely to be employed (48.9 %) than the impaired (26.1 %) group (p = 0.025). We defined a group of MS patients deemed cognitively intact on conventional neuropsychological testing, but who, nevertheless, had deficits relative to premorbid intellectual abilities. The high premorbid IQ in this group does not prevent, but ‘softens’ the impact of cognitive decline. These findings provide novel evidence supporting cognitive reserve as a protective factor in relation to cognitive dysfunction in MS.     

The neuropsychology of de novo patients with idiopathic Parkinson's disease: the effects of age of onset

One hundred de novo patients with Parkinson's disease (PD) were classified into two groups according to age of onset of symptoms. Seventy two patients were under 70 years and 28 were 70 years and over. All patients were given neurological and neuropsychological assessments, and the severity of the signs was rated on a modified Columbia scale. The neuropsychological assessment was also administered to 50 age-and-education-matched controls. The neuropsychological test battery included tests of verbal learning, visual memory, verbal fluency, visuospatial skill, simple and choice reaction time, language and maze learning. The late-onset patients had significant impairment in nonverbal reasoning, auditory verbal learning, visual memory and choice reaction time in contrast to early-onset patients and controls. A relationship was found between bradykinesia and widespread cognitive impairment. Severity of tremor was found to be significantly correlated with impairment in auditory verbal learning, visual memory and increased choice reaction time, while rigidity was found to be associated with cognitive impairment in verbal fluency and visuospatial skill. Using DSM II criteria, 39% of the late-onset and 8% of the early-onset group were classified as demented. Dementia was more common in patients with bilateral symmetrical disease and in those patients with marked tremor and bradykinesia. The pattern of cognitive impairment in PD was consistent with that associated with a subcortical dementia. This study confirms that the expression of PD is markedly influenced by the age of onset.     

The effects of adjunctive topiramate on cognitive function in patients with epilepsy

PURPOSE: We investigated possible cognitive effects of topiramate (TPM) in polypharmacy on patients with intractable epilepsy. METHODS: Study 1 evaluated 22 consecutively admitted patients whose antiepileptic drugs (AEDs) on admission to the Montreal Neurological Hospital included TPM. Performance on neuropsychological tests administered on and subsequently off TPM was analyzed. Four patients also were tested before taking TPM, allowing comparisons off, then on, and then off the drug again. Measures included intellectual function, verbal and nonverbal memory, language, word and design fluency, somatosensory sensitivity, and motor skills. In Study 2, 16 patients at the Minnesota Epilepsy Group were tested first off, then on TPM with nine cognitive tasks that measured concentration, verbal fluency, language, and psychomotor speed. RESULTS: In Study 1, significant (p < or = 0.01) improvements were observed off TPM on 13 measures including verbal and nonverbal fluency and certain verbal and perceptual tasks. Notably, verbal learning and memory were unaffected; a limited effect was observed on nonverbal memory. Patients tested 3 times scored better in both tests off TPM compared with on this drug. In Study 2, declines on TPM were observed on all measures, significantly (p < or = 0.05) for tests of fluency, sustained concentration, and visual motor processing speed. CONCLUSIONS: TPM was associated with declines in fluency, attention/concentration, processing speed, language skills, and perception; working memory but not retention was affected. As the two studies used an opposite order of testing on versus off TPM, our results clearly show a performance decrement while patients are taking TPM, without respect to which condition is tested first.     

The influence of antiepileptic drugs on cognition: a comparison of levetiracetam with topiramate

Levetiracetam (LEV) and topiramate (TPM) are considered highly effective novel antiepileptic drugs (AEDs) in the treatment of focal epilepsies. To explore potential side effects, this study investigated their influence on cognitive functions comparatively by means of a standardized neuropsychological test battery assessing several cognitive domains. In this observational study, cognitive changes were explored in 30 consecutively recruited patients with focal epilepsy treated with LEV and in 21 patients treated with TPM, comparing functions assessed prior to gradual initiation and after reaching steady state of the individual target dosage. Before titration, patient groups did not differ significantly with respect to cognitive performance. Whereas the LEV group manifested no change in cognitive performance after AED titration, the TPM group worsened in the cognitive domains of cognitive speed and verbal fluency, as well as short-term memory. These findings suggest that TPM, unlike LEV, may impair frontal lobe functions. The lack of cognitive side effects related to LEV treatment may be relevant for treatment decisions.     

Neuropsychological changes 1-year after subthalamic DBS in PD patients: A prospective controlled study

ObjectiveThis study aimed at investigating the neuropsychological effect of DBS of the Subthalamic Nucleus in patients with advanced Parkinson's disease (PD).MethodsA standardized neuropsychological test battery, assessing reasoning, memory and executive functions, was administered to 27 PD patients who underwent DBS-STN (DBS group) and to a matched control group of 31 PD patients under optimal medical treatment (MED group). Patients were evaluated at baseline and at the end of 1 year.ResultsChange score analysis (T1 minus T0 scores) demonstrated a significant decline in phonemic verbal fluency in the DBS group compared with the MED group (p < 0.005), while there were no significant changes between the two groups for the other cognitive tests. Single cases analysis by means of multivariate normative comparisons revealed that 4 out of 27 DBS patients (15%) showed cognitive deterioration one year post surgery. These patients were significantly more compromised from a motor standpoint (UPDRS, section III) than the 23 DBS PD patients who had no cognitive decline post surgery.ConclusionResults of this prospective controlled-study showed that phonemic verbal fluency declined one year after DBS-STN, while the other cognitive domains did not change significantly. Nevertheless, single case analysis highlighted the fact that a subgroup comprising 15% of DBS-STN patients (4/27) showed significant cognitive decline 1 year after surgery.     

Kognitive Beeinträchtigungen unter Add-on-Therapie mit Topiramat

In an open study, 37 epilepsy patients were investigated with regard to cognitive impairments in anticonvulsant add-on therapy with topiramate (TPM). In addition to a preexisting antiepileptic medication, TPM administration was started and increased by 25 mg/week. Cognitive side effects noted by the patient or doctor were assessed by a neuropsychological test battery. In 18/37 patients (49%), cognitive deficits consisting of impaired concentration, psychomotoric slowing, memory deficits, and dysphasia were observed. The adverse effects became apparent at dosages of 50-575 mg TPM/day (average 210 mg). In four patients, they were reversible after reducing the dose of TPM by 25-150 mg/day. In eight patients, the adverse effects led to withdrawal of TPM. In spite of slow titration, the present study showed a higher frequency of cognitive side effects under TPM than was previously reported. In some patients, these side effects led to substantial impairments in daily life and at work. For early recognition of cognitive impairments, neuropsychological baseline and follow-up investigations of verbal fluency, psychomotor processing speed, and verbal memory are recommended.     

抑郁症和早期阿尔茨海默病的记忆和执行功能

目的 研究抑郁症和早期阿尔茨海默病(AD)的神经心理学特征,试图运用神经心理学评估对两者进行鉴别。方法 对32例单相抑郁症、38例早期AD和34例对照进行WHO-UCLA词语学习、词语流畅、复杂图形和逻辑记忆的评估。结果 早期AD组神经心理学测验得分最低,抑郁症组次之,对照组最高,3组之间有显著性差异(P<0.01);抑郁症组仅表现为词语学习和逻辑记忆的自由回忆以及语义流畅的损害(P<0.05),而早期AD组表现为全面的认知功能损害(P<0.01);逐步判别分析提示,复杂图形延迟自由回忆、词语学习长时延迟自由回忆和语义流畅是区分抑郁症组和早期AD组的重要指标。结论 抑郁症和早期AD认知功能损害的特征不同,长时延迟自由回忆、再认和语义流畅能够区分早期AD和抑郁症。     

Neuropsychological profile of patients with juvenile myoclonic epilepsy: a controlled study of 50 patients

The purpose of this study was to verify possible cognitive dysfunction in patients with juvenile myoclonic epilepsy (JME) and its relationship to factors related to epilepsy and schooling. Fifty subjects diagnosed with JME and 50 controls underwent neuropsychological assessment evaluating intellectual functions, attention, memory, executive functions, and language. The patients were further divided into two subgroups on the basis of educational level: < or = 11 and >11 years of formal education. Participants diagnosed with JME scored significantly below age-, education-, and gender-matched controls on neuropsychological measures of attention, immediate verbal memory, mental flexibility, control of inhibition, working memory, processing speed, verbal delayed memory, visual delayed memory, naming, and verbal fluency. A positive correlation was observed between duration of epilepsy and cognitive decline. However, in the group of patients with >11 years of education, this correlation was not significant. In this series of patients with JME, neuropsychological evaluation suggests widespread cognitive dysfunction outside the limits of the frontal lobes. The duration of epilepsy correlated with cognitive decline, and patients with higher education manifested less progression of deficits.     

Cognitive dysfunction in people with convulsive seizures in rural China

One hundred and forty-four people with convulsive seizures (CS) and 144 healthy controls were evaluated for cognitive function, using a battery of neuropsychological tests. People with CS performed significantly worse than the controls on the Mini-Mental State Examination, Hamilton Depression Rating Scale, auditory verbal learning test, digit span test, verbal fluency test, and digit cancellation test. The percentage of patients who had abnormal scores on the Hamilton Depression Rating Scale was higher than that of controls (54.9% vs. 7.6%, p<0.001). Cognitive functional impairment was detected in 65.3% of the patients and 29.2% of the controls (p<0.001). People with CS presented with depressive mood and a wide range of cognitive deficits, particularly deficits in episodic declarative memory, attentional capacity, semantic memory, and mental speed. Years in education were positively associated with the cognitive performance of people with CS (OR=0.655, 95% CI: 0.486-0.882, p=0.005).     

Validity of cognitive complaints in substance-abusing patients and non-clinical controls: The Patient's Assessment of Own Functioning Inventory (PAOFI)

To determine the validity of substance-abusing (SA) patients' self-reports of cognitive impairments, we assessed the independent contributions of depression, actual neurocognitive performance and an index of cognitive decline, in predicting cognitive complaints in groups of SA patients and normal controls. The SA sample comprised 74 veterans enrolled in day treatment. The non-clinical sample consisted of 150 English-speaking adults. Assessment instruments were as follows: A modified version of the Patient's Assessment of Own Functioning Inventory (PAOFI) containing three subscale on: Memory, Language and Communication, and Higher Cognitive Functions; the Beck Depression Inventory; a battery of neuropsychological tests that measured domains of executive function, processing speed, verbal fluency and verbal and visual memory; and a measure of premorbid intellectual functioning. SA patients reported twice as many PAOFI complaints as non-clinical controls. SA patients' neuropsychological performance was lower than that of non-clinical controls. A higher percentage of SA patients had significant cognitive decline. The SA sample reported more depression. There was no association between PAOFI scores and neuropsychological performance for either group. PAOFI results were not associated with cognitive decline. BDI scores accounted for 12% of the variance in PAOFI total score for the SA sample and 44% for the non-clinical sample in multiple regression analysis. Cognitive complaints were related more to depression than cognitive performance for both SA and non-clinical samples. The results do not support self-report as a valid means of neuropsychological assessment in SA samples, although self-reports may provide other information about perceived cognitive difficulties that may be relevant to clinical evaluation.     

Cognitive rehabilitation in Multiple sclerosis

Cognitive impairments are frequent in Multiple sclerosis (MS). However, most studies about efficacy of cognitive rehabilitation interventions have been criticized in terms of methods and/or design. The aim of this study is to evaluate the efficacy of cognitive rehabilitation in MS patients with a cognitive intervention (ProCogSEP* program), compared to a control intervention (discussion program). Twenty MS patients have completed this simple blind study: 10 patients followed 13 sessions (2 hours) of the ProCog-SEP¹ program. Ten other patients followed 13 sessions (2 hours) of a discussion program (Control Group). All patients underwent neuropsychological assessment, before and after their program, in order to evaluate cognitive functions. Two neuropsychologists respectively assessed the patients and conducted the group sessions. Compared to its own baseline, ProCog-SEP Group show improvements in verbal memory [free recall (p = .02), learning (p = .002)], in visual memory [free (p = .05) and delayed recall (p = .007)], in working-memory (p = .03), in verbal fluency (p = .05) and in language (p = .01). Inter group analysis show a benefit of cognitive program mainly in verbal and visual memory, and in verbal fluencies. These results support the interest of a cognitive therapeutic management of MS patients.     

The role of the intracarotid amobarbital procedure in predicting verbal memory decline after temporal lobe resection

PURPOSE: The aim of this study was to compare the utility of baseline neuropsychological measures and scores from the intracarotid amobarbital procedure (IAP) in the prediction of postoperative memory decline in temporal lobe epilepsy surgery patients. METHODS: Logistic regression analyses were used to determine the relation between demographic variables, baseline neuropsychological scores, and scores from the IAP (using mixed verbal and nonverbal stimuli) and postoperative deterioration in verbal learning and verbal recall in 91 patients (48 right, RTL; 43 left, LTL) who had undergone a standard anterior temporal lobe resection for the relief of medically intractable epilepsy and who had been followed up 1 year postoperatively. RESULTS: In the RTL group, the IAP scores were not significant predictors of a postoperative decline in verbal learning or recall. In the LTL group, postoperative decline in verbal learning was associated with good preoperative baseline scores, an older age at the time of surgery, and an unexpected asymmetry on the IAP. Baseline neuropsychological scores and scores from the IAP were associated with a significant postoperative decline in verbal recall in the LTL group. CONCLUSIONS: Scores from the IAP using mixed stimuli were not helpful in the prediction of postoperative verbal memory decline in RTL patients. The significance of IAP scores in predicting verbal memory deficits in LTL patients may be task specific.     

The clinical significance of neuropsychological changes following bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease

Despite the clinical importance of the question, a number of methodological issues have limited firm conclusions regarding the cognitive safety of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD). Amongst these issues, studies have generally failed to consider the postoperative changes that occur within individual patients. This study utilized reliable change indices (RCIs) derived from a PD sample to determine the frequency of clinically significant postoperative decline on a battery of neuropsychological measures. This approach addresses measurement reliability, potential practice effects, and disease progression. The proportion of patients experiencing clinically significant postoperative decline on measures of list learning and verbal fluency was greater than expected based on disease progression; however, the majority of patients (55%) did not experience a significant decline in performance on any of the cognitive tests administered, and only one experienced decline on more than one test. Therefore, the statistically significant declines on measures of list learning and verbal fluency observed in the sample as a whole were the result of clinically significant declines experienced by a minority of participants.     

Neuropsychological and quality of life outcomes 12 months after unilateral thalamic stimulation for essential tremor

OBJECTIVES: To evaluate the one year cognitive, mood state, and quality of life (QoL) outcomes of unilateral thalamic deep brain stimulation (DBS) for essential tremor (ET). METHODS: 40 patients diagnosed with ET completed comprehensive neuropsychological assessments about one month before and three and 12 months after DBS electrode implantation. Data were subjected to multivariate analyses, and significant results were further analysed using univariate techniques. RESULTS: Analyses revealed statistically significant improvements on a cognitive screening measure and in aspects of fine visuomotor and visuoperceptual functions, verbal memory, mood state, and QoL. No group-wise declines in cognition were observed, but more patients showed declines than improvements on language and visual memory tests. Semantic verbal fluency declined significantly in four (10%) of the patients. In these four patients, diminished lexical verbal fluency was present at baseline. CONCLUSION: Cognitive, mood, and QoL outcomes after one year of DBS for ET are favourable; there were no overall deleterious effects on cognition, and DBS was accompanied by a significant reduction in anxiety and improvements in quality of life. However, preoperative verbal fluency diminution may predispose to further fluency declines after DBS.     

Freezing of gait in Parkinson's disease: The paradoxical interplay between gait and cognition

BackgroundFreezing of gait is a disabling episodic gait disturbance common in patients with Parkinson's disease. Recent evidences suggest a complex interplay between gait impairment and executive functions.Aim of our study was to evaluate whether specific motor conditions (sitting or walking) influence cognitive performance in patients with or without different types of freezing.MethodsEight healthy controls, eight patients without freezing, nine patients with levodopa-responsive and nine patients with levodopa-resistant freezing received a clinical and neuropsychological assessment during two randomly performed conditions: at rest and during walking.ResultsAt rest, patients with levodopa-resistant freezing performed worse than patients without freezing on tests of phonological fluency (p = 0.01). No differences among the four groups were detected during walking. When cognitive performances during walking were compared to the performance at rest, there was a significant decline of verbal episodic memory task (Rey Auditory Verbal Learning Test) in patients without freezing and with levodopa-responsive freezing. Interestingly, walking improved performance on the phonological fluency task in patients with levodopa-resistant freezing (p = 0.04).ConclusionsCompared to patients without freezing, patients with levodopa-resistant freezing perform worse when tested while seated in tasks of phonological verbal fluency. Surprisingly, gait was associated with a paradoxical improvement of phonological verbal fluency in the patients with levodopa-resistant freezing whilst walking determined a worsening of episodic memory in the other patient groups.     

Cognitive impairment patterns in Parkinson's disease with visual hallucinations.

OBJECTIVES: We investigated the role of stage of disease, motor status and dopaminergic treatment in cognitive impairment of Parkinson's disease (PD) patients with visual hallucination (VH) and the presence of specific cognitive impairment patterns. METHOD: We compared 33 PD patients with VH (group 1) with 30 PD patients without VH (group 2) with regard to demographic characteristics and neuropsychological test scores. RESULTS: The group with VH demonstrated significantly worse Short Test of Mental Status scores; the cognitive impairment pattern presented in the form of frontal dysfunction and memory deterioration. There were significant differences in Stroop duration/error, verbal fluency, Wechsler Memory Scale and Sozel Bellek Surecleri Test (a Turkish verbal learning test) scores. CONCLUSION: In PD patients with VH the main pattern of cognitive impairment is frontal dysfunction and memory deterioration. Because visual perceptive functions were not different between the two groups, such deterioration may not be a primary factor in the development of VH.     

Cognitive function in early psychosis patients from a lower middle-income country

Objectives: To establish evidence of cognitive changes in early psychosis (EP) patients compared to healthy controls (HC) in Pakistan.

Methods: Fifty-one participants with EP were recruited from psychiatric units in Karachi and Rawalpindi, Pakistan and matched with 51 HC. Neurocognitive domains were assessed using standardised neuropsychological tests [the Stroop test, block design, Matrix Reasoning, picture completion, object assembly, oral fluency, memory for design, Coughlan learning task (verbal and visual)].

Results: EP patients had higher scores than controls for both Stroop tests (T1: EP?=?122 HC?=?65, p?<.001; T2: EP?=?190 HC?=?153, p?=?.007) and memory for design test (EP?=?10 HC?=?3, p?=?.005). EP group had lower values for block design (EP?=?4, HC?=?11, p?=?.01), category fluency (EP?=?18.9, HC?=?26.1, p?p?p?p?=?.003) and object assembly (EP?=?10.7, HC?=?15.5, p?=?.002). There were limited significant associations between cognitive performance and PANSS scores.

Conclusions: Reduced cognitive performance was found across multiple domains in Pakistani EP patients, which suggests that impaired cognitive performance is homogenous in patients with schizophrenia, regardless of ethnicity.     

Cognitive and psychiatric effects of topiramate monotherapy in migraine treatment: an open study

Few data are available on cognitive and psychiatric effects of topiramate (TPM) monotherapy in migraine. Twenty patients affected by migraine were treated with TPM monotherapy. At the same time, twenty control subjects were selected. A comprehensive neuropsychological and behavioural battery of tests were performed at baseline (T0), at titration (T1) and in maintenance period (T2). Topiramate serum levels were also investigated at T1 and T2. On comparison with the control group, no cognitive and psychiatric differences were detected at baseline. A significant reduction of word fluency score ( P  < 0.05) was evident after TPM treatment, both at T1 and T2. No patient developed psychiatric adverse events. TPM induced an impairment of verbal fluency and no psychiatric adverse events, demonstrating selective negative cognitive profile in migraine therapy. Slow titration, low doses, lack of previous psychiatric disorders and/or familial history may explain our data.