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- Almkvist, O, et al.
(författare)
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Mild cognitive impairment -- An early stage of Alzheimer´s disease?
- 1998
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Ingår i: Journal of Neural Transmission. ; 53, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that mild cognitive impairment (MCI) represents an early stage of Alzheimer´s disease (AD) was investigated by reviewing recent research from three sources: asymptomatic and symptomatic individuals carrying mutations that cause AD; hospital
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- Bosnes, O., et al.
(författare)
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Including a subject-paced trial may make the PASAT more acceptable for MS patients
- 2015
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 132:4, s. 219-225
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Tidskriftsartikel (refereegranskat)abstract
- The Paced Auditory Serial Addition Test (PASAT) is regularly used in the evaluation of cognition in multiple sclerosis (MS). However, the test may impose frustration, distress, and anxiety in patients, which may result in refusal to participate by many patients. ObjectivesIn this study, a subject- and experimenter-paced PASAT was compared and analyzed, with regard to independent measures of cognitive functions, as well as disability, fatigue, depression, and anxiety. MethodsA population-based sample of patients with MS (n=34; mean age 47.28.6) was examined with the PASAT, including a subject-paced condition, in addition to the standard experimenter-paced conditions using three levels of interstimuli intervals (ISI: 3.0, 2.5, and 2.0s). A comprehensive set of neuropsychological tests, measures of disease severity, fatigue, anxiety, and depression were studied as potentially associated factors. ResultsSubject- and experimenter-paced PASAT performance correlated significantly and the subject-paced administration correlated even higher with measures of information processing speed, executive function, attention, and working memory than standard experimenter-paced administration of PASAT. DiscussionThe associations between PASAT performance and measures of fatigue, anxiety, and depression were not significant. ConclusionThe results indicate that the altered PASAT procedure measures the same cognitive functions in MS as the standard procedure. At the same time, the altered procedure may make the PASAT more user-friendly for patients with MS.
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- Eyjolfsdottir, H., et al.
(författare)
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Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device
- 2016
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion. Methods: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day. Results: All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable. Conclusions: The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.
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| 5. |
- Winblad, B, et al.
(författare)
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Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.
- 2004
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Ingår i: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 256:3, s. 240-6
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Forskningsöversikt (refereegranskat)abstract
- The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.
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- Almkvist, O, et al.
(författare)
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Responder characteristics to a single oral dose of cholinesterase inhibitor: a double-blind placebo-controlled study with tacrine in Alzheimer patients
- 2001
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:1, s. 22-32
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Tidskriftsartikel (refereegranskat)abstract
- A proportion of Alzheimer’s disease (AD) patients treated for several months with cholinesterase (ChE) inhibitors have shown some favorable response on cognition, but the characteristics of the responders are still unclear. This study attempts to identify the characteristics of individuals with a positive behavioral response after a double-blind randomized administration of a single oral dose of tacrine (40 mg) and placebo to AD patients. Furthermore, the relationship between single-dose and long-term responders are examined. Twenty-four mildly to very mildly demented AD patients participated in the study. They all fulfilled the diagnosis of probable AD according to NINCDS-ADRDA criteria. Active treatment (tacrine 40 mg) and placebo was administered in random order on 2 consecutive days, and the effects were evaluated within 2 h using neuropsychological tests (assessing visuospatial ability, episodic memory and attention), registration of EEG activity and measurement of red blood cells (RBC) acetylcholinesterase (AChE), ChE activity and concentrations of tacrine and its metabolites in plasma. Results demonstrated significant improvement, tacrine compared to placebo, in measures of attention, but not in episodic memory or visuospatial ability. A single-dose response was therefore defined in terms of improvement in attention. The tacrine plasma concentration (pcTHA) showed a positively skewed distribution (mean ± SD: 10.5 ± 11.8, range: 1.0–51.8 ng/ml). There were no significant differences between single-dose responders compared to nonresponders in pcTHA, metabolites of tacrine, inhibition of AChE in RBC, tau levels in CSF, AChE activity in CSF or plasma and demographic variables. However, single-dose responders showed a higher right frontal alpha/theta ratio on EEG and had lower glucose metabolism in the parietal-temporal association cortex at baseline. In addition, the frequency of apolipoprotein E (APOE) Ε4 alleles was higher in responders. Interestingly, the single-dose response was related to the long-term response, although not significantly, which probably was due to lack of power. To conclude, the present study identified single-dose responders in terms of improved attentional performance associated with a relatively higher alpha/theta activity in the right frontal regions of the brain measured on EEG and predominance of APOE Ε4 allele.
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- Axelman, K, et al.
(författare)
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Life situation, coping and quality of life in people with high and low risk of developing Alzheimer's disease
- 2003
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 16:4, s. 220-228
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Tidskriftsartikel (refereegranskat)abstract
- The psychosocial consequences of being at different risk for inheriting Alzheimer’s disease (AD) were investigated in a high-risk group (n = 106) and a low-risk group (n = 37). Non-affected individuals from families with AD in two or more generations answered questions about their life situation, quality of life and coping. Their answers were compared with a population sample (n = 408). The high-risk group assessed the quality of their personal relationships and everyday life higher than did the population sample. They also used less emotive and supportive coping strategies compared with the population sample. Nearly 90% in the high-risk group felt anxiety concerning their own risk or the risk of their children and grandchildren of developing AD. About 50% of the respondents complained about a lack of information. The pieces of information they asked for were early signs of the disease, treatment, and practical information on how to handle everyday life with an affected relative.
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- Backman, L, et al.
(författare)
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Functional changes in brain activity during priming in Alzheimer's disease
- 2000
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Ingår i: JOURNAL OF COGNITIVE NEUROSCIENCE. - : M I T PRESS. - 0898-929X. ; 12:1, s. 134-141
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Tidskriftsartikel (refereegranskat)abstract
- Patients with Alzheimer's disease (AD) are often impaired on certain forms of implicit memory, such as word-stem completion priming (WSCP). Lesion data suggest that deficient WSCP may be associated with abnormal functioning in the posterior neocortex. Usi
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| 48. |
- Bäckman, Lars, et al.
(författare)
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Brain regions associated with episodic retrieval in normal aging and Alzheimer's disease
- 1999
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Ingår i: NEUROLOGY. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878. ; 52:9, s. 1861-1870
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine patterns of brain activation during verbal episodic retrieval in normal elderly subjects and patients in an early phase of AD. Background: It is established that 1) a profound episodic memory impairment is a cardinal symptom of AD;
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| 49. |
- Claesson, IM, et al.
(författare)
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Rapid cognitive screening in multiple sclerosis accomplished by the Free Recall and Recognition Test
- 2007
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:2, s. 272-274
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Tidskriftsartikel (refereegranskat)abstract
- This study sought to investigate the feasibility of the Free Recall and Recognition Test (FRRT) as a practical screening tool for cognitive impairment in multiple sclerosis (MS). Persons with MS (n =227) were consecutively recruited and assessed with four cognitive tests; FRRT, Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and the Mini-Mental State Examination (MMSE). Disease severity was assessed by the Expanded Disability Status Scale (EDSS). The FRRT, which was completed by 99% of the cohort in approximately 5 minutes per assessment, correlated significantly with the other cognitive tests, as well as with the disease severity rating. A cut-off of 4 for the FRRT recall rendered 90% sensitivity and 25% specificity, and a cut-off of 4.2 for the FRRT recognition resulted in 70% sensitivity and 51% specificity. We conclude that the FRRT proved feasible as a practical screening tool for cognitive impairment in MS within a clinical setting. Multiple Sclerosis 2007; 13: 272–274. http://msj.sagepub.com
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| 50. |
- Darreh-Shori, T., et al.
(författare)
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Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in AD patients treated with galantamine
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:2, s. 168-184
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between acetylcholinesterase (AChE) activity in the CSF and brain of patients with Alzheimer's disease (AD) was investigated in 18 mild AD patients following galantamine treatment. The first 3 months of the study had a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16-24 mg/day) and six patients placebo. This was followed by 9 months Galantamine treatment in all patients. Activities and protein levels of both the "read-through" AChE (AChE-R) and the synaptic (AChE-S) variants in CSF were assessed in parallel together with the regional brain AChE activity by C-11-PMP and PET. The AChE-S inhibition was 30-36% in CSF, which correlated well with the in vivo AChE inhibition in the brain. No significant AChE inhibition was observed in the placebo group. The increased level of the AChE-R protein was 16% higher than that of AChE-S. Both the AChE inhibition and the increased level of AChE-R protein positively correlated with the patient's performance in cognitive tests associated with visuospatial ability and attention. In conclusion, AChE levels in CSF closely mirror in vivo brain AChE levels prior to and after treatment with the cholinesterase inhibitors. A positive cognitive response seems to dependent on the AChE inhibition level, which is balanced by an increased protein level of the AChE-R variant in the patients.
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