Towards the concept of disease-modifier in post-stroke or vascular cognitive impairment: a consensus report.

BACKGROUND: Vascular cognitive impairment (VCI) is a complex spectrum encompassing post-stroke cognitive impairment (PSCI) and small vessel disease-related cognitive impairment. Despite the growing health, social, and economic burden of VCI, to date, no specific treatment is available, prompting the introduction of the concept of a disease modifier. CONSENSUS AND SUGGESTIONS: Within this clinical spectrum, VCI and PSCI remain advancing conditions as neurodegenerative diseases with progression of both vascular and degenerative lesions accounting for cognitive decline. Disease-modifying strategies should integrate both pharmacological and non-pharmacological multimodal approaches, with pleiotropic effects targeting (1) endothelial and brain-blood barrier dysfunction; (2) neuronal death and axonal loss; (3) cerebral plasticity and compensatory mechanisms; and (4) degenerative-related protein misfolding. Moreover, pharmacological and non-pharmacological treatment in PSCI or VCI requires valid study designs clearly stating the definition of basic methodological issues, such as the instruments that should be used to measure eventual changes, the biomarker-based stratification of participants to be investigated, and statistical tests, as well as the inclusion and exclusion criteria that should be applied. CONCLUSION: A consensus emerged to propose the development of a disease-modifying strategy in VCI and PSCI based on pleiotropic pharmacological and non-pharmacological approaches.

Admission into a Nursing Home. Delay or prevention with the use of a complete support network?

BACKGROUND: Becoming older in Germany often leads to admission into a nursing home. OBJECTIVE: The aim of this study was to investigate if a complete support network (CSN) can contribute to preventing admission into a nursing home. Organizational and financial prerequisites of a CSN were documented. MATERIAL AND METHODS: In this study 32 patients with psychiatric disorders diagnosed according to the International Classification of Diseases 10 (ICD 10, 16 as F00 dementia in Alzheimer disease and 16 as F31-33 bipolar affective disorder, depressive episode and recurrent depressive disorder) were observed over a period of 2 years. The intervention consisted of participation in a defined CSN, which was developed by the Alexian Research Centre in Krefeld (ARCK). A cooperation of all persons and institutions involved in the care of elderly patients with psychiatric disorders was initiated. An individualized help plan was compiled for each patient. The primary outcome was admittance to a nursing home or remaining at home. The duration of staying at home was measured in days. User satisfaction was assessed with a 5­step Likert scale questionnaire. The steering process and the financial efforts necessary to run the CSN were descriptively evaluated. RESULTS: At the end of the observation period 28 out of 32 patients were not admitted to a nursing home. During the observational period one patient dropped out, one died and two were admitted to a nursing home. User satisfaction achieved a median score of 5 (very satisfied). No additional funding was necessary to run the CSN. CONCLUSION: The CSN can prevent admission to a nursing home without needing additional funding and the whole process can be guided by the patient.

World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of dementias in primary care.

OBJECTIVE: To define a practice guideline for biological treatment of dementias for general practitioners in primary care. METHODS: This paper is a short and practical summary of the World Federation of Biological Psychiatry (WFSBP) guidelines for the Biological treatment of Alzheimer's disease and other dementias for treatment in primary care ( Ihl et al. 2011 ). The recommendations were developed by a task force of international experts in the field and are based on randomized controlled studies. RESULTS: Anti-dementia medications neither cure, nor arrest, or alter the course of the disease. The type of dementia, the individual symptom constellation and the tolerability and evidence for efficacy should determine what medications should be used. In treating neuropsychiatric symptoms, psychosocial intervention should be the treatment of first choice. For neuropsychiatric symptoms, medications should only be considered when psychosocial interventions are not adequate and after cautious risk-benefit analysis. CONCLUSIONS: Depending on the diagnostic entity and clinical presentation different anti-dementia drugs can be recommended. These guidelines provide a practical approach for general practitioners managing dementias.

Multielectrode array analysis of cerebrospinal fluid in Alzheimer's disease versus mild cognitive impairment: a potential diagnostic and treatment biomarker.

Pathological cerebrospinal fluid (CSF) alterations like changes in amyloid-ß1-42 and tau protein concentration are typical in Alzheimer's disease (AD). However, it remains unclear, if the composition of known or unknown pathological factors in native CSF has a functional significance in AD. In this pilot study, we used multielectrode array (MEA) neurochips to determine whether CSF of individuals with AD (AD-CSF) may have distinct neurofunctional properties that may distinguish it from that of individuals with mild cognitive impairment (MCI) - a differential diagnosis of high clinical importance. MEAs are neuronal cultures coupled to a multisite electrical recording system with the ability to reflect pharmacological or toxicological alterations on the functional level of whole neuronal networks. Collective rhythmical electrical activity was substantially enhanced after exposure to CSF of cognitively healthy subjects (controls) and of MCI individuals (MCI-CSF) alike. However, this activity increment was significantly reduced when MEAs were exposed to AD-CSF compared to MCI-CSF. Moreover, following AD-CSF exposure, networks showed significantly enhanced burst durations and less synchronous bursting, respectively. Thus, AD-CSF and MCI-CSF could be distinguished by characteristic changes of the network firing pattern on MEAs. When data of MCI individuals and AD patients were pooled, the network suppression correlated significantly with the degree of cognitive decline. The findings of this pilot study may set the stage for a unique and straightforward diagnostic bioassay of AD with particular value in the differential diagnosis to MCI and as a much needed biomarker for clinical trials.

Memantine effects measured with the Relevant Outcome Scale for Alzheimer's disease in an open-label, single-arm, multicenter clinical study.

OBJECTIVE: The Relevant Outcome Scale for Alzheimer's disease (ROSA) is a novel, valid, and reliable instrument for multidimensional assessment of Alzheimer's disease (AD) symptoms across all severity stages. The ROSA and four standard instruments -- the Alzheimer's disease Assessment Scale-cognitive (ADAS-cog), Severe Impairment Battery (SIB), Disability Assessment for Dementia (DAD), and the Neuropsychiatric Inventory (NPI) -- were used in an open-label, multicenter, single-arm clinical study to assess treatment-induced changes in cognitive, functional, and behavioral symptoms in patients with AD at different severity stages. METHODS: A total of 451 patients were treated with memantine (initiated at 5 mg/day and up-titrated with 5 mg weekly to a final dose of 20 mg/day) for 12 weeks. The study endpoints comprised changes from baseline in the scores of the ROSA, ADAS-cog, SIB, DAD, and NPI as well as global changes on the Clinical Global Impression of Change (CGI-C). Analyses were performed for the overall population and by AD severity stage (early, middle, late). RESULTS: The ROSA scores increased significantly after a 12-week treatment in all study groups except for early stage. Mean changes in the ADAS-cog score indicated a trend towards worsening in early and middle stages. Non-significant changes were shown by the SIB, NPI, and DAD assessments at week 12. The CGI-C demonstrated 'minimal improvement' or 'no change' for most of the patients. Overall, memantine treatment was safe and well tolerated. CONCLUSION: The results demonstrated the ROSA feasibility in daily practice for assessment of memantine effects over time in patients with moderate and late AD.

Sensitivity to change of composite and frequency scores of the Neuropsychiatric Inventory in mild to moderate dementia.

BACKGROUND: The Neuropsychiatric Inventory (NPI) is widely used to assess psychopathology in dementia. The scoring involves ratings of frequency and severity, as well as the calculation of a composite score. It was suggested recently that, due to lower variance, the frequency score might be more sensitive to detect treatment-related change and to discriminate active treatment from placebo than the composite score, particularly in milder forms of the disease. METHODS: Based on data from three randomized controlled trials in patients with mild to moderate dementia, standardized changes were calculated for both frequency and composite scores for two strata of disease severity. The two strata were formed by dichotomizing the sample along the median score of the short cognitive performance test (SKT) battery. RESULTS: Across all studies and for both severity strata, standardized changes in frequency scores were not consistently larger than those in composite scores and both scores discriminated active treatment from placebo at similar probabilities for type-1 error. CONCLUSION: Our findings do not support the notion that there is a difference between frequency score and composite score with respect to their sensitivity to treatment-related change.

Effects of Ginkgo biloba extract EGb 761 ® in dementia with neuropsychiatric features: review of recently completed randomised, controlled trials.

OBJECTIVE: We review four randomised, controlled trials investigating the efficacy of Ginkgo biloba extract EGb 761(®) in elderly patients with Alzheimer or vascular dementia with neuropsychiatric features. METHODS: Patients with a total score of 9-23 in the Syndrom-Kurz test (SKT) cognitive test battery (cognitive domain) and with a composite score 6 and greater in the Neuropsychiatric Inventory (NPI; behavioural domain) were included. Three trials compared 2 × 120 mg/day or 1 × 240 mg/day EGb 761(®) to placebo while one used donepezil as an active control. The duration of randomised treatment was 22 or 24 weeks. RESULTS: One thousand, two hundred and ninety-four patients were analysed for efficacy. Patients treated with EGb 761(®) showed improvements of cognitive performance and behavioural symptoms that were associated with advances in activities of daily living and a reduced burden to caregivers. Placebo-treated patients, on the other hand, showed only minimal improvements or signs of progression. In each placebo-controlled trial, EGb 761(®) was significantly superior in all mentioned domains (p < 0.01). In the actively controlled trial, EGb 761(®) and donezepil as well as a combination of both drugs had similar effects. CONCLUSIONS: The review supports the efficacy of EGb 761(®) in age-related dementia with neuropsychiatric features. The drug was safe and well-tolerated.

Detecting treatment effects with combinations of the ADAS-cog items in patients with mild and moderate Alzheimer's disease.

OBJECTIVE: When complex cognitive functions are measured with multi-item scales like the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), it seems valuable information can be lost due to combination of the ADAS-cog items results into a total score. We hypothesized, that an analysis of the results of different ADAS-cog item combinations may reveal drug treatment effects in distinct cognitive domains and/or enhance the sensitivity to detect such treatment effects. Here, we present a novel approach called 'subsetting analysis' for assessment of drug treatment effects with multi-item scales, like the ADAS-cog. METHODS: The subsetting approach is a mathematical algorithm designed to select and group scale items in a subset detecting drug treatment effects in a particular study population. The approach was applied in a post-hoc analysis of ADAS-cog results from two randomized, placebo-controlled and double-blind clinical trials with memantine in mild to moderate Alzheimer's disease (AD). The subsetting analysis of the ADAS-cog combined database aimed at selecting the scale items showing no worsening at study end compared to baseline due to memantine treatment in mild AD (Mini-Mental State Examination (MMSE >19)) patients. RESULTS: Two ADAS-cog subsets were finally revealed by the analysis: a subset of five ADAS-cog items, identified as most sensitive to memantine effects in mild AD patients, and a subset of six ADAS-cog items shown to detect significant memantine effects in moderate AD patients. CONCLUSION: The subsetting approach of analyzing ADAS-cog data is a powerful alternative for gaining information about drug effects on cognitive performance in mild and moderate AD patients.

Gingko biloba extract EGb 761®: clinical data in dementia.

Research into Gingko biloba extract EGb 761® has been ongoing for many years. Early studies showed that the extract was superior to placebo in improving symptoms of dementia, and this has been confirmed by more recent research. The GINDEM-NP, GOTADAY and GOT-IT! studies showed that 240 mg/day EGb 761® improved cognitive function, neuropsychiatric symptoms, activities of daily living, and quality of life in patients with mild to moderate dementia compared with placebo, with results reproducible in independent trials. The strength of the effect in terms of improvements in neurosensory symptoms associated with old age and dementia was strong enough to be detected by caregivers and independent clinicians. A combination of 240 mg/day EGb 761® and 10 mg/day (initially 5 mg/day) donepezil was also more effective than either drug alone. Regarding the improvement of neuropsychiatric symptoms, a cross-comparison of studies with different antidementia agents suggests that EGb 761® is at least as effective as memantine, galantamine, and donepezil. Safety data revealed no important safety concerns with EGb 761®.

A survey of geriatric psychiatry training across Europe.

BACKGROUND: Training, practice, and continuing professional development in old age psychiatry varies across Europe. The aims of this study were to survey current practice and develop recommendations to begin a debate on harmonization. METHODS: A survey was sent out to 38 European countries via email. The survey was sent to members of the European Association of Geriatric Psychiatry (EAGP) Board, members of the World Psychiatric Association, and key old age psychiatrists or other psychiatrists with a special interest in the area for countries where old age psychiatry was not formally a specialty. RESULTS: Through a process of networking, we identified a key individual from each country in Europe to participate in this study, and 30 out of 38 (79%) representatives responded. Training programs and duration varied between countries. Eleven countries reported that they had geriatric psychiatry training programs and most of these required geriatric psychiatry trainees to complete mandatory training for two years within old age psychiatry. Representatives from ten countries reported having specific Continuing Professional Development (CPD) for old age psychiatrists at consultant level. CONCLUSION: There is a clear indication that the recognition of geriatric psychiatry as a specialist discipline in Europe is on the rise. The training procedures and processes in place vary considerably between and sometimes within countries. There are several options for harmonizing old age psychiatry training across Europe with advantages to each. However, support is required from national old age psychiatry bodies across Europe and an agreement needs to be reached on a training strategy that encompasses supervision, development, and appraisal of the knowledge and skills sets of old age psychiatrists.

Ginkgo biloba extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease: a research perspective.

In June 2011 a two-day expert meeting "The Ageing Brain" took place in Amsterdam, The Netherlands. The main aim was to discuss the available preclinical and clinical data on Ginkgo biloba special extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease. 19 dementia experts covering the disciplines bio- and neurochemistry, gerontology, neurology, pharmacology, and psychiatry from Australia, Asia, Europe and North America reviewed available preclinical and clinical data for EGb 761® and identified core topics for future research. Based on a wide range of preclinical effects demonstrated for Ginkgo biloba, EGb 761® can be conceptualized as a multi-target compound with activity on distinct pathophysiological pathways in Alzheimer's disease (AD) and age-related cognitive decline. While symptomatic efficacy in dementia and mild cognitive impairment (MCI) has been demonstrated, interpretation of data from dementia prevention trials is complicated by important methodological issues. Bridging pre-clinical research and clinical research as well as deciding on suitable study designs for future trials with EGb 761® remain important questions. The participants of the "Ageing Brain" meeting on Ginkgo biloba special extract EGb 761® concluded that there is plenty of promising data, both pre-clinical and clinical, to consider future research with the compound targeting cognitive impairment in old age as a worthwhile activity.

Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomized controlled trial.

OBJECTIVE: To test the efficacy and safety of a once-daily formulation of EGb 761 in the treatment of patients with dementia with neuropsychiatric features. METHODS: Multi-centre trial of 410 outpatients with mild to moderate dementia (Alzheimer's disease, vascular dementia or mixed form) scoring between 9 and 23 on the SKT cognitive test battery, at least five on the Neuropsychiatric Inventory (NPI) and three or higher in at least one item of the NPI. Patients were randomly allocated to double-blind treatment with 240 mg of EGb 761 or placebo once daily for 24 weeks. Primary outcomes were the changes from baseline in the SKT total score and the NPI total score. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC), Activities of Daily Living International Scale (ADL-IS), NPI distress score, DEMQOL-Proxy quality-of-life scale and Verbal Fluency Test were secondary outcomes. RESULTS: At endpoint, patients treated with EGb 761 (n = 202) improved by -1.4 (95% confidence interval -1.8; -1.0) points on the SKT and by -3.2 (-4.0; -2.3) on the NPI total score, whereas those receiving placebo (n = 202) deteriorated by +0.3 (-0.1; 0.7) on the SKT and did not change on the NPI total score (-0.9; 0.9). Both drug-placebo comparisons were significant at p < 0.001. EGb 761 was significantly superior to placebo with respect to all secondary outcome measures. Adverse event rates were similar for both treatment groups. CONCLUSIONS: EGb 761, 240 mg once-daily, was found significantly superior to placebo in the treatment of patients with dementia with neuropsychiatric symptoms.

Strategies for the use of Ginkgo biloba extract, EGb 761® , in the treatment and management of mild cognitive impairment in Asia: Expert consensus.

BACKGROUND: Mild cognitive impairment (MCI) is a neurocognitive state between normal cognitive aging and dementia, with evidence of neuropsychological changes but insufficient functional decline to warrant a diagnosis of dementia. Individuals with MCI are at increased risk for progression to dementia; and an appreciable proportion display neuropsychiatric symptoms (NPS), also a known risk factor for dementia. Cerebrovascular disease (CVD) is thought to be an underdiagnosed contributor to MCI/dementia. The Ginkgo biloba extract, EGb 761® , is increasingly being used for the symptomatic treatment of cognitive disorders with/without CVD, due to its known neuroprotective effects and cerebrovascular benefits. AIMS: To present consensus opinion from the ASian Clinical Expert group on Neurocognitive Disorders (ASCEND) regarding the role of EGb 761® in MCI. MATERIALS & METHODS: The ASCEND Group reconvened in September 2019 to present and critically assess the current evidence on the general management of MCI, including the efficacy and safety of EGb 761® as a treatment option. RESULTS: EGb 761® has demonstrated symptomatic improvement in at least four randomized trials, in terms of cognitive performance, memory, recall and recognition, attention and concentration, anxiety, and NPS. There is also evidence that EGb 761® may help delay progression from MCI to dementia in some individuals. DISCUSSION: EGb 761® is currently recommended in multiple guidelines for the symptomatic treatment of MCI. Due to its beneficial effects on cerebrovascular blood flow, it is reasonable to expect that EGb 761® may benefit MCI patients with underlying CVD. CONCLUSION: As an expert group, we suggest it is clinically appropriate to incorporate EGb 761® as part of the multidomain intervention for MCI.

Treatment effects of Memantine on language in moderate to severe Alzheimer's disease patients.

BACKGROUND: Language impairment is one of the most troublesome manifestations of Alzheimer's disease (AD). The objective of this post hoc analysis was to assess the treatment effects of Memantine on language in patients with moderate to severe AD, using the recently developed Severe Impairment Battery-Language (SIB-L) scale. METHODS: From a combined database including four Memantine clinical trials in moderate-to-severe AD, we analyzed 801 patients with SIB-L scores of <38 and Mini-Mental State Examination scores of <15. Patients were treated with either 20 mg Memantine per day or placebo. Mean changes in SIB-L scores from baseline were calculated. For responder analyses, a change in SIB-L score greater than or equal to the SIB-L measurement error of 3.7 points was considered a clinically relevant response. RESULTS: The mean change from baseline in SIB-L score at week 12 and weeks 24/28 (study end) significantly favored Memantine over placebo treatment (P < .0001 and P = .0182, respectively). Overall, more Memantine-treated patients than placebo-treated patients benefited from treatment. The effect was especially pronounced in patients with substantial language impairment on the SIB-L (baseline score,

Severe Impairment Battery Language scale: a language-assessment tool for Alzheimer's disease patients.

BACKGROUND: Communication problems are common in Alzheimer's disease (AD) patients, but instruments to assess these symptoms are limited. Our objective was to create a new scale, based on the language subscale of the Severe Impairment Battery (SIB), as a sensitive and reliable measurement of treatment effects on language performance. METHODS: All 24 items of the SIB language subscale were chosen for analysis. Baseline scores of 1320 moderate-to-severe patients (Mini-Mental State Examination [MMSE] score, <15), from a combined AD database of four Memantine clinical trials (Study Codes: IE-2101, MEM-MD-01, MEM-MD-02, and MRZ-9605), were used for item reduction according to a standard principal components factor analysis. All items with loadings >0.5 on the identified factors were selected for inclusion in the new language scale. Correlations with existing AD scales were examined. RESULTS: The analysis indicated six factors, with 21 of 24 items showing loadings >0.5. The resulting 21-item SIB Language (SIB-L) scale exhibited high internal consistency (Cronbach's alpha = 0.809). The maximal SIB-L score was 41 points, with a measurement error of 3.7 points. The stratification of baseline SIB-L scores (mean, 31.7; SD, 8.4) by MMSE scores (mean, 9.7; SD, 3.3) showed a high variance in SIB-L scores. This confirms that patients with a low MMSE score can possess preserved language abilities. The SIB-L scale did not exhibit substantial floor-and-ceiling effects. CONCLUSIONS: The new SIB-L is a fast (<15 minutes) and easily administered scale with favorable psychometric characteristics for assessing language impairment and treatment effects on the language performance of patients with moderate to severe AD.

Therapeutic efficacy of the Ginkgo special extract EGb761® within the framework of the mitochondrial cascade hypothesis of Alzheimer's disease.

OBJECTIVES: The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction as an important common pathomechanism for the whole spectrum of age-associated memory disorders from cognitive symptoms in the elderly over mild cognitive impairment to Alzheimer's dementia. Thus, a drug such as the Ginkgo special extract EGb 761® which improves mitochondrial function should be able to ameliorate cognitive deficits over the whole aging spectrum. METHODS: We review the most relevant publications about effects of EGb 761® on cognition and synaptic deficits in preclinical studies as well as on cognitive deficits in man from aging to dementia. RESULTS: EGb 761® improves mitochondrial dysfunction and cognitive impairment over the whole spectrum of age-associated cognitive disorders in relevant animal models and in vitro experiments, and also shows clinical efficacy in improving cognition over the whole range from aging to Alzheimer's or even vascular dementia. CONCLUSIONS: EGb 761® shows clinical efficacy in the treatment of cognitive deficits over the whole spectrum of age-associated memory disorders. Thus, EGb 761® can serve as an important pharmacological argument for the mitochondrial cascade hypothesis of dementia.

Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761®.

BACKGROUND: The Ginkgo biloba special extract, EGb 761® has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer's disease (AD). METHODS: To guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence-based consensus recommendations regarding the use of EGb 761® in neurocognitive disorders with/without cerebrovascular disease. RESULTS: Key randomized trials and robust meta-analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761® versus placebo in patients with mild-to-moderate dementia. In those with mild cognitive impairment (MCI), EGb 761® has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761® with the same strength of evidence as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761® had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761® to have a positive risk-benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta-analyses have not supported this association. CONCLUSIONS: The Expert Group foresee an important role for EGb 761® , used alone or as an add-on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761® should be used in alignment with local clinical practice guidelines.

Quantitative EEG in progressing vs stable mild cognitive impairment (MCI): results of a 1-year follow-up study.

OBJECTIVE: The study objective is to evaluate the use of qEEG data for the cross-sectional differentiation of mild cognitive impairment (MCI) from mild Alzheimer's disease (AD) and in the longitudinal prediction of cognitive decline in MCI. METHODS: Eighty-eight subjects with MCI and 42 subjects with mild probable AD were enrolled. Baseline EEGs were recorded using a 32-channel system with electrode positioning according to the international 10-20 system. Digitalized EEG data were further studied by quantitative spectral analysis. Study subjects were followed up for 1 year and reassessed psychometrically. An increase of the total ADAS-cog score of >or= 4 points was regarded as a significant cognitive decline. Using this cut-off, MCI subjects were sub-grouped into stable MCI (s-MCI) and progressing MCI (p-MCI). RESULTS: AD subjects and p-MCI subjects were differentiated from s-MCI subjects by a reduction of alpha power over posterior leads. Reduction of alpha power and mean frequency were significantly correlated with poorer cognitive performance in psychometric tests. Baseline values of alpha power over posterior leads had the highest positive predictive power for MCI and AD (69-80%) and predicted cognitive decline in MCI within a 1-year follow up. CONCLUSIONS: qEEG revealed decreased alpha activity in progressing MCI and mild AD prior to an increase of slow wave activity, which typically occurs in advancing AD. This finding may reflect an affection of thalamo-cortical relay activity and cortical connectivity in the early disease course of AD. Reduced alpha activity in MCI subjects at baseline may have prognostic value regarding future cognitive decline.

Ginkgo biloba extract EGb 761® alleviates neurosensory symptoms in patients with dementia: a meta-analysis of treatment effects on tinnitus and dizziness in randomized, placebo-controlled trials.

BACKGROUND: Tinnitus and dizziness are frequent in old age and often seen as concomitant symptoms in patients with dementia. In earlier clinical trials, Ginkgo biloba extract EGb 761® was found to alleviate tinnitus and dizziness in elderly patients. Consequently, a meta-analysis was conducted to evaluate the effects of EGb 761® at a daily dose of 240 mg on tinnitus and dizziness associated with dementia. METHODS: Randomized, placebo-controlled clinical trials of G. biloba extract EGb 761® identified by a systematic database search were included in a meta-analysis if they met all of the following selection criteria: 1) diagnosis of dementia according to generally accepted criteria, 2) treatment period of at least 20 weeks, 3) outcome measures covering at least two of the three conventional domains of assessment, 4) presence and severity of dizziness and tinnitus were assessed, and 5) assessment was done before and after randomized treatment. RESULTS: Five trials that met the inclusion criteria were included in the meta-analysis. The risk of bias was judged as low, with Jadad scores of 3 and 5. In all trials, 11-point box scales were used to assess the severity of tinnitus and dizziness. Overall, EGb 761® was superior to placebo, with weighted mean differences for change from baseline, calculated in meta-analyses using random effects models, of -1.06 (95% CI: -1.77, -0.36) for tinnitus (p = 0.003) and -0.77 (95% CI: -1.44, -0.09) for dizziness (p = 0.03). CONCLUSION: Our findings support the notion that EGb 761® is also effective in alleviating concomitant neurosensory symptoms in patients with dementia.