| 1. |
- 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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| 2. |
- Engedal, K, et al.
(författare)
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Quantitative EEG Applying the Statistical Recognition Pattern Method: A Useful Tool in Dementia Diagnostic Workup
- 2015
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 40:1-2, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aim:</i></b> The aim of this study was to examine the discriminatory power of quantitative EEG (qEEG) applying the statistical pattern recognition (SPR) method to separate Alzheimer's disease (AD) patients from elderly individuals without dementia and from other dementia patients. <b><i>Methods:</i></b> The participants were recruited from 6 Nordic memory clinics: 372 unselected patients [mean age 71.7 years (SD 8.6), 54% women] and 146 healthy elderly individuals [mean age 66.5 years (SD 7.7), 60% women]. After a standardized and comprehensive assessment, clinical diagnoses were made according to internationally accepted criteria by at least 2 clinicians. EEGs were recorded in a standardized way and analyzed independently of the clinical diagnoses, using the SPR method. <b><i>Results:</i></b> In receiver operating characteristic curve analyses, the qEEGs separated AD patients from healthy elderly individuals with an area under the curve (AUC) of 0.90, representing a sensitivity of 84% and a specificity of 81%. The qEEGs further separated patients with Lewy body dementia or Parkinson's disease dementia from AD patients with an AUC of 0.9, a sensitivity of 85% and a specificity of 87%. <b><i>Conclusion:</i></b> qEEG using the SPR method could be a useful tool in dementia diagnostic workup.
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| 3. |
- Ferreira, D, et al.
(författare)
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Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers
- 2016
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 42:1-2, s. 80-92
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> Dementia biomarkers that are accessible and easily applicable in nonspecialized clinical settings are urgently needed. Quantitative electroencephalography (qEEG) is a good candidate, and the statistical pattern recognition (SPR) method has recently provided promising results. We tested the diagnostic value of qEEG-SPR in comparison to cognition, structural imaging, and cerebrospinal fluid (CSF) biomarkers. <b><i>Methods:</i></b> A total of 511 individuals were recruited from the multicenter NORD EEG study [141 healthy controls, 64 subjective cognitive decline, 124 mild cognitive impairment, 135 Alzheimer's disease (AD), 15 dementia with Lewy bodies/Parkinson's disease with dementia (DLB/PDD), 32 other dementias]. The EEG data were recorded in a standardized way. Structural imaging data were visually rated using scales of atrophy in the medial temporal, frontal, and posterior cortex. <b><i>Results:</i></b> qEEG-SPR outperformed structural imaging, cognition, and CSF biomarkers in DLB/PDD diagnosis, outperformed structural imaging in AD diagnosis, and improved the differential diagnosis of AD. In addition, qEEG-SPR allowed differentiation of two clinically different AD subtypes. <b><i>Conclusion:</i></b> Adding qEEG to the diagnostic workup substantially increases the detection of AD pathology even in pre-dementia stages and improves differential diagnosis. EEG could serve as a good complement to currently established dementia biomarkers since it is cheap, noninvasive, and extensively applied outside academic centers.
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| 4. |
- Herholz, K, et al.
(författare)
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Impairment of neocortical metabolism predicts progression in Alzheimer's disease
- 1999
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:6, s. 494-504
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Tidskriftsartikel (refereegranskat)abstract
- Progression rates of Alzheimer’s disease (AD) vary considerably, and they are particularly difficult to predict in patients with mild cognitive impairment. We performed a prospective multicenter cohort study in 186 patients with possible or probable AD, mostly with presenile onset. In a cross-sectional analysis at entry, impairment of glucose metabolism in temporoparietal or frontal association areas measured with positron emission tomography was significantly associated with dementia severity, clinical classification as possible versus probable AD, presence of multiple cognitive deficits and history of progression. A prospective longitudinal analysis showed a significant association between initial metabolic impairment and subsequent clinical deterioration. In patients with mild cognitive deficits at entry, the risk of deterioration was up to 4.7 times higher if the metabolism was severely impaired than with mild or absent metabolic impairment.
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| 5. |
- Jelic, V, et al.
(författare)
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Donepezil treatment of severe Alzheimer's disease in nursing home settings. A responder analysis
- 2008
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 26:5, s. 458-466
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Our objective was to define clinically meaningful outcomes in donepezil versus placebo treatment in severe Alzheimer’s disease (AD) and to describe characteristics of responders. <i>Methods:</i> Analyses were performed on data from a 6-month, double-blind, parallel-group, placebo-controlled study on the efficacy of donepezil in 248 nursing home residents. Various individual responses were defined as stabilisation or improvement on the Severe Impairment Battery (SIB), Alzheimer’s Disease Cooperative Study-activities of daily living scale (ADCS-ADL), Mini-Mental State Examination, Neuropsychiatric Inventory (NPI) or Clinical Global Impression of Improvement. Three composite measures were defined by combining the individual response criteria on these outcomes. The impact of baseline disease severity and of concomitant use of psychotropic drugs was also analysed. <i>Results:</i> At 6 months, greater proportions of patients defined as responders to donepezil on individual efficacy measures showed significant stabilisation or improvement compared with placebo on the SIB (≧0, ≧4 or ≧7 points) and Mini-Mental State Examination (≧0 or ≧3 points), and positive trends on the ADCS-ADL-severe (≧3 points) and the NPI cluster based on mood items. All 3 composite measures of efficacy showed a significantly higher proportion of responders in the donepezil group. The responders had a similar distribution between the 2 subgroups of cognitive and functional disease severity at baseline. The donepezil-treated patients taking psychotropic drugs showed significantly greater improvement on the SIB, less deterioration on the ADCS-ADL, and had higher Clinical Global Impression of Improvement scores and a trend towards lower NPI scores. The baseline demographic and clinical profile did not differ between the non-responders and responders on the composite outcome measures. <i>Conclusion:</i> The results demonstrate that donepezil treatment of patients with severe AD consistently shows stabilisation or improvement across multiple outcome measures in individual patients, including cognitive, functional and behavioural symptoms.
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| 6. |
- Jelic, V, et al.
(författare)
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Quantitative electroencephalography power and coherence in Alzheimer's disease and mild cognitive impairment
- 1996
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Ingår i: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 7:6, s. 314-323
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Tidskriftsartikel (refereegranskat)abstract
- In this study the best combination of quantitative electroencephalographic variables (qEEG) for the discrimination of groups with mild to moderate Alzheimer''s disease (AD), mild cognitive impairment and healthy subjects was defined and related to neuropsychological performance. The study population included 18 patients with mild to moderate probable AD, 19 subjects with objective memory disturbances, 17 subjects with subjective memory complaints who did not have clinical evidence of memory disturbance, and 16 healthy controls. AD patients had significantly increased theta and decreased alpha relative power, mean frequency, and temporoparietal coherence. There was no significant difference in the mean frequency in the left temporal region between AD patients and subjects with objective memory disturbances. Temporoparietal coherence appeared as a discriminant variable together with alpha and theta relative power only between AD patients and controls, giving 77.8% sensitivity and 100% specificity. Significant correlations between regional changes in qEEG variables and cognitive functions were found.
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| 7. |
- Kramberger, Milica Gregoric, et al.
(författare)
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Association between EEG abnormalities and CSF biomarkers in a memory clinic cohort
- 2013
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 36:5-6, s. 319-328
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the study was to describe distinct electroencephalogram (EEG) phenotypes defined after routine visual EEG analysis in a large memory clinic cohort and to investigate their relationship to cerebrospinal fluid (CSF) biomarkers. Methods: Patients with Alzheimer's disease (n = 131), mild cognitive impairment (n = 285), subjective cognitive impairment (n = 310), and mixed dementia (n = 29) were assessed clinically with neuroimaging, EEG and CSF investigations. EEG phenotypes were based on frequency of background activity (BA) and presence and degree of episodic abnormalities (EA). Results: BA and EA differed significantly (p < 0.001) between diagnostic groups. A lower CSF amyloid β42/phospho-tau ratio and higher total tau were associated with slower BA (p < 0.01) and a higher degree of EA (p < 0.04). Conclusions: Slowing of BA in combination with EA seems to be related to biological markers of neurodegeneration
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| 8. |
- Lindau, M, et al.
(författare)
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Quantitative EEG abnormalities and cognitive dysfunctions in frontotemporal dementia and Alzheimer's disease
- 2003
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 15:2, s. 106-114
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Tidskriftsartikel (refereegranskat)abstract
- <i>Objective:</i> To investigate the relationship between quantitative EEG (qEEG) measurements in frontotemporal dementia (FTD), Alzheimer’s disease (AD) and healthy controls and to study to what extent qEEG in FTD and AD or neuropsychological test results of FTD and AD patients or a combination of both contribute to classification accuracy. <i>Method:</i> The FTD sample consisted of 19 patients, the AD sample of 16 patients, and the control group of 19 subjects. Groups were matched on the group level with respect to demographic variables. For qEEG the global field power was calculated for six frequency bands: δ (1.0–3.5 Hz), Θ (4.0–7.5 Hz), α (8.0–11.0 Hz), β1 (12.0–15.5 Hz), β2 (16.0–19.5 Hz), β3 (20.0–23.5 Hz), and spectral ratio as the ratio of the sum of fast frequency bands α + β1 + β2 + β3 and slow frequency bands δ + Θ. <i>Results:</i> In comparison to controls FTD patients were marked by an absence of an increase in slow qEEG activities and a decrease in fast activities, whereas AD patients were marked by an increase in slow activities and a smaller decrease in fast activities. According to the Mann-Whitney U test the cognitive functions of attention, visuospatial thinking and episodic memory were significantly better in FTD than in AD. Using logistic regression analysis the best predictors of FTD and AD were in a model using the δ and Θ activities, and high levels of visuospatial ability and episodic memory. Classification accuracy of the model was 93.3%. <i>Conclusion:</i> FTD patients reveal a different pattern of qEEG changes than AD patients. This result demonstrates the importance of qEEG for FTD diagnosis. Cognition is selectively better in FTD than in AD. A combination of qEEG and neuropsychology is recommended for differential diagnoses of FTD and AD.
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| 9. |
- Wahlund, LO, et al.
(författare)
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A follow-up study of the family with the Swedish APP 670/671 Alzheimer's disease mutation
- 1999
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:6, s. 526-533
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Tidskriftsartikel (refereegranskat)abstract
- <i>Objective:</i> To study the progression of Alzheimer’s disease (AD) at a very early stage and to evaluate clinical markers of presymptomatic AD. <i>Setting:</i> Longitudinal study at a university hospital. <i>Subjects:</i> A Swedish family harboring a double mutation at codons 670/671 of the APP gene on chromosome 21 was followed longitudinally for 3 years. Both mutation carriers and noncarriers participated. <i>Outcome Measurements:</i> Results from clinical investigations, electroencephalography, neuropsychological and neuroradiological examinations including magnetic resonance imaging, single-photon emission computed tomography and positron emission tomography were assessed and compared on two or more occasions. <i>Main Outcome:</i> During follow-up, 1 initially asymptomatic mutation carrier who was near the expected age of onset for this family, developed cognitive symptoms, and at the end of the follow-up fulfilled the diagnostic criteria for AD. One mutation carrier with cognitive symptoms at the first examination showed clinical deterioration and was diagnosed with AD. One demented mutation carrier died and was shown to have typical AD neuropathology at autopsy. The two remaining asymptomatic mutation carriers, as well as all the noncarriers were asymptomatic. These mutation carriers who were near the expected age of onset of AD but without clinical signs of the disease, did not show changes in either electrophysiological parameters or volumes of the temporal lobes. However, in these 2 individuals the blood flow in the temporal lobe showed intermediate values between the symptomatic mutation carriers and healthy noncarriers. Two neuropsychological tests showed a deterioration that paralleled clinical symptoms in 1 of the mutation carriers who was close to the expected age of onset and who at the end of the follow-up had clinical signs of AD. In the same subject, brain glucose metabolism was pathologically reduced in the temporal lobes before other clinical symptoms were obvious. <i>Conclusion:</i> In this familial form of AD a reduced temporal lobe glucose metabolism was indicative of AD before the expected clinical onset. Reduced glucose metabolism even preceded the development of subjective or objective cognitive dysfunction and might therefore serve as a clinical marker for AD before the onset of clinical symptoms. Reduced cerebral blood flow in the temporal lobes and cognitive deterioration paralleled the clinical decline in the early stage of the disease.
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| 10. |
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