The Effect of Cannabidiol 3% on Neuropsychiatric Symptoms in Dementia - Six-Month Follow-Up.

OBJECTIVES: To investigate the beneficial outcomes of giving cannabidiol (CBD) 3% over a six-month period in the BPSD, the management of which is a crucial issue for everyday clinical praxis and to compare the progress in BPSD of patients who receive Cannabidiol 3% with those who follow usual medical treatment (UMT) in everyday clinical praxis. METHODS: A total of 20 PwD with severe BPSD were recruited from the database of Alzheimer Hellas with NPI score >30. Ten of them were assigned to UMT, while ten were assigned to a six-month treatment with CBD drops. The follow-up assessment was performed with NPI, both clinically and by structured telephone interview. RESULTS: The follow-up assessment with NPI showed significant improvement of the BPSD in all our patients who received CBD, and no or limited improvement in the second group, regardless of the underlying neuropathology of dementia. CONCLUSIONS: We suggest that CBD may be a more effective and safe choice for managing BPSD than the typical intervention. Future large randomized clinical trials are needed to re-assure these findings. CLINICAL IMPLICATIONS: Healthcare professionals should consider incorporating CBD 3% into their practices to reduce BPSD in PwD. Regular assessments are necessary to ensure long-term effectiveness.

Web-Based Intervention Effects on Mild Cognitive Impairment Based on Apolipoprotein E Genotype: Quasi-Experimental Study.

BACKGROUND: Apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and mild cognitive impairment (MCI). Computer-based training programs can improve cognitive performance in elderly populations. However, the effects of computer-based interventions on MCI APOE ε4 carriers have never been studied before. OBJECTIVE: The effects of different web-based interventions and the APOE isoform-specific differences in training outcomes are investigated. METHODS: Using a quasi-experimental study design, 202 participants with MCI aged 60 years and older took part in three different intervention programs (physical and cognitive [Long-Lasting Memories, or LLM], cognitive [Active Control, or AC], or physical intervention [Physical Training Control, or PTC]) via an innovative information and communication technologies exergaming platform. Participants in each interventional group were subdivided into APOE ε4 carriers and non-APOE ε4 carriers. All participants underwent an extensive neuropsychological evaluation before and after the training, blood tests, and brain imaging. RESULTS: All interventions resulted in multiple statistically significant cognitive benefits after the intervention. Verbal learning (California Verbal Learning Test: immediate recall test score-LLM: P=.04; AC: P<.001), working memory (digit span forward and backward test scores-AC: P=.03; PTC: P=.02 and P=.006, respectively), and long-term memory (California Verbal Learning Test: delayed recall test score-LLM: P=.02; AC: P=.002; and PTC: P=.02) were improved. There was no statistically significant difference among the intervention effects. APOE ε4 presence moderates intervention effects as the LLM intervention improved only their task-switching processing speed (Trail Making Test, Part B: P=.03) and the PTC intervention improved only the working memory (digit span backward: P=.03). No significant performance alteration was noted for the APOE ε4+ cognitive AC training group. CONCLUSIONS: None of the applied interventions could be identified as the optimal one; it is suggested, however, that combined cognitive and physical training and physical training via exergaming may be more effective for the high-risk MCI ΑPOE ε4+ subgroup.

Prevalence of Apolipoprotein E Polymorphisms in Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study.

BACKGROUND: Apolipoprotein E ε4 allele (APOEε4) is a major genetic risk factor for Alzheimer's disease (AD). APOEε4 carriers have a higher risk of cognitive impairment and AD in a gene dose-dependent manner. The above notion is investigated in the Greek population. METHODS: A sample of 1,703 subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc., USA). Descriptive statistics, one-way analysis of variance with Bonferroni post hoc tests, Pearson chi-square test, and binary logistic regression models were used for the statistical analysis. RESULTS: The APOE genotype and allele frequencies in AD group were significantly different from those in the Control and MCI groups. The frequencies of ε4/4 homozygotes were 1.9, 1.6, and 5.7%, while the ε4/- carriers' distribution was 22.5, 24.1, and 37.4% in the Control, MCI, and AD groups respectively. The estimated odds of ε4/4 for AD was 5.731-fold higher compared to the estimated odds of ε3/3. The interaction between gender and APOE did not have a significant effect on the odds for MCI (p = 0.942) and AD (p = 0.984). CONCLUSION: In Greece, APOE ε4 presence is related to an increased risk for AD in a dose-related manner. Contrary to long-standing views, men and women with the APOE ε4 genotype have nearly the same odds of developing MCI and AD.

Language Markers of Dementia and Their Role in Early Diagnosis of Alzheimer's Disease: Exploring Grammatical and Syntactic Competence via Sentence Repetition.

Background: Earlier research focuses primarily on the cognitive changes due to Alzheimer's disease (AD); however, little is known with regard to changes in language competence across the lifespan. Objective: The present study aims to investigate the decline of language skills at the grammatical and syntactic levels due to changes in cognitive function. Methods: We administered the Litmus Sentence Repetition Task (SRT) to 150 native speakers of Greek who fall into five groups: 1) young healthy speakers, 2) cognitively intact elder healthy speakers, 3) speakers with subjective cognitive impairment (SCI), 4) speakers with mild cognitive impairment (MCI); and 5) speakers with AD dementia at the mild/moderate stages. All participants underwent a physical and neurological examination and cognitive screening with a standardized neuropsychological battery to assess cognitive status comprehensively and evaluate aspects like working memory, executive function, attention and memory to appropriately classify them. Results: The data analysis revealed that the SRT had high discriminatory value in the development of AD; specifically, both accuracy and grammaticality indices were related to cognitive decline. Additionally, syntax significantly affected the performance of speakers with structures such as clitics being particularly challenging and in most structures the performance of speakers with MCI drops significantly compared to speakers with SCI. Conclusions: Linguistic indices revealed subtle early signs of cognitive decline that can be helpful in the early detection of AD, thus facilitating the clinical process offering support to language-based assessment tools such as sentence repetition, a non-invasive type of assessment to evaluate symptoms of AD.

Assessing the Linguistic Capacity Across Alzheimer's Disease and Its Preclinical Stages: Evidence from Narrative Macrostructure in Elderly Speakers of Greek.

Background: The assessment of language deficits can be valuable in the early clinical diagnosis of neurodegenerative disorders, including Alzheimer's disease (AD). Objective: The present study aims to explore whether language markers at the macrostructural level could assist with the placement of an individual across the dementia continuum employing production data from structured narratives. Methods: We administered a Picture Sequence Narrative Discourse Task to 170 speakers of Greek: young healthy controls (yHC), cognitively intact healthy elders (eHC), elder participants with subjective cognitive impairment (SCI), with mild cognitive impairment (MCI), and with AD dementia at the mild/moderate stages. Structural MRIs, medical history, neurological examination, and neuropsychological/cognitive screening determined the status of each speaker to appropriately groupthem. Results: The data analysis revealed that the Macrostructure Index, Irrelevant Info, and Narration Density markers can track cognitive decline and AD (p < 0.001; Macrostructural Index: eHC versus AD Sensitivity 93.8%, Specificity 74.4%, MCI versus AD Sensitivity 93.8%, Specificity 66.7%; Narration Density: eHC versus AD Sensitivity 90.6%, Specificity 71.8%, MCI versus AD Sensitivity 93.8%, Specificity 66.7%). Moreover, Narrative Complexity was significantly affected for subjects with AD, Irrelevant Info increased in the narrations of speakers with MCI and AD, while Narration Length did not appear to indubitably differentiate between the cognitively intact groups and the clinical ones. Conclusions: Narrative Macrostructure Indices provide valuable information on the language profile of speakers with(out) intact cognition revealing subtle early signs of cognitive decline and AD suggesting that the inclusion of language-based assessment tools would facilitate the clinical process.

Exploring Network Properties Across Preclinical Stages of Alzheimer's Disease Using a Visual Short-Term Memory and Attention Task with High-Density Electroencephalography: A Brain-Connectome Neurophysiological Study.

BACKGROUND: Visual short-term memory (VSTMT) and visual attention (VAT) exhibit decline in the Alzheimer's disease (AD) continuum; however, network disruption in preclinical stages is scarcely explored. OBJECTIVE: To advance our knowledge about brain networks in AD and discover connectivity alterations during VSTMT and VAT. METHODS: Twelve participants with AD, 23 with mild cognitive impairment (MCI), 17 with subjective cognitive decline (SCD), and 21 healthy controls (HC) were examined using a neuropsychological battery at baseline and follow-up (three years). At baseline, the subjects were examined using high density electroencephalography while performing a VSTMT and VAT. For exploring network organization, we constructed weighted undirected networks and examined clustering coefficient, strength, and betweenness centrality from occipito-parietal regions. RESULTS: One-way ANOVA and pair-wise t-test comparisons showed statistically significant differences in HC compared to SCD (t (36) = 2.43, p = 0.026), MCI (t (42) = 2.34, p = 0.024), and AD group (t (31) = 3.58, p = 0.001) in Clustering Coefficient. Also with regards to Strength, higher values for HC compared to SCD (t (36) = 2.45, p = 0.019), MCI (t (42) = 2.41, p = 0.020), and AD group (t (31) = 3.58, p = 0.001) were found. Follow-up neuropsychological assessment revealed converge of 65% of the SCD group to MCI. Moreover, SCD who were converted to MCI showed significant lower values in all network metrics compared to the SCD that remained stable. CONCLUSION: The present findings reveal that SCD exhibits network disorganization during visual encoding and retrieval with intermediate values between MCI and HC.

Challenges at the APOE locus: a robust quality control approach for accurate APOE genotyping.

BACKGROUND: Genetic variants within the APOE locus may modulate Alzheimer's disease (AD) risk independently or in conjunction with APOE*2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE. The APOE locus however remains relatively poorly understood in AD, owing to multiple challenges that include its complex linkage structure and uncertainty in APOE*2/3/4 genotype quality. Here, we present a novel APOE*2/3/4 filtering approach and showcase its relevance on AD risk association analyses for the rs439401 variant, which is located 1801 base pairs downstream of APOE and has been associated with a potential regulatory effect on APOE. METHODS: We used thirty-two AD-related cohorts, with genetic data from various high-density single-nucleotide polymorphism microarrays, whole-genome sequencing, and whole-exome sequencing. Study participants were filtered to be ages 60 and older, non-Hispanic, of European ancestry, and diagnosed as cognitively normal or AD (n = 65,701). Primary analyses investigated AD risk in APOE*4/4 carriers. Additional supporting analyses were performed in APOE*3/4 and 3/3 strata. Outcomes were compared under two different APOE*2/3/4 filtering approaches. RESULTS: Using more conventional APOE*2/3/4 filtering criteria (approach 1), we showed that, when in-phase with APOE*4, rs439401 was variably associated with protective effects on AD case-control status. However, when applying a novel filter that increases the certainty of the APOE*2/3/4 genotypes by applying more stringent criteria for concordance between the provided APOE genotype and imputed APOE genotype (approach 2), we observed that all significant effects were lost. CONCLUSIONS: We showed that careful consideration of APOE genotype and appropriate sample filtering were crucial to robustly interrogate the role of the APOE locus on AD risk. Our study presents a novel APOE filtering approach and provides important guidelines for research into the APOE locus, as well as for elucidating genetic interaction effects with APOE*2/3/4.

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

Greek High Phenolic Early Harvest Extra Virgin Olive Oil Reduces the Over-Excitation of Information-Flow Based on Dominant Coupling Mode (DoCM) Model in Patients with Mild Cognitive Impairment: An EEG Resting-State Validation Approach.

BACKGROUND: Extra virgin olive oil (EVOO) constitutes a natural compound with high protection over cognitive function that could positively alter brain dynamics and the mixture of within and between-frequency connectivity. OBJECTIVE: The balance of cross-frequency coupling over within-frequency coupling can build a nonlinearity index (NI) that encapsulates the over-excitation of information flow between brain areas and across experimental time. The present study investigated for the very first time how the Greek High Phenolic Early Harvest Extra Virgin Olive Oil (HP-EH-EVOO) versus Moderate Phenolic (MP-EVOO) and Mediterranean Diet (MeDi) intervention in people with mild cognitive impairment (MCI) could affect their spontaneous EEG dynamic connectivity. METHODS: Forty-three subjects (14 in MeDi, 16 in MP-EVOO, and 13 in HP-EH-EVOO) followed an EEG resting-state recording session (eyes-open and closed) before and after the treatment. Following our dominant coupling mode model, we built a dynamic integrated dynamic functional connectivity graph that tabulates the functional strength and the dominant coupling mode model of every pair of brain areas. RESULTS: Signal spectrum within 1-13 Hz and theta/beta ratio have decreased in the HP-EH-EVOO group in the eyes-open condition. The intervention improved the FIDoCM across groups and conditions but was more prominent in the HP-EH-EVOO group (p < 0.001). Finally, we revealed a significant higher post-intervention reduction of NI (ΔNITotal and α) for the HP-EH-EVOO compared to the MP-EVOO and MeDi groups (p < 0.0001). CONCLUSION: Long-term intervention with HP-EH-EVOO reduced the over-excitation of information flow in spontaneous brain activity and altered the signal spectrum of EEG rhythms.

Stroke associated with Mycoplasma hominis infection: a case report.

BACKGROUND: Mycoplasmas are the smallest prokaryotic microorganisms in nature. Many cases of stroke post-Mycoplasma pneumoniae infection have been reported, particularly in the pediatric population. However, Mycoplasma hominis infection has not previously been associated with stroke. CASE PRESENTATION: We report the case of a 36-year-old Greek woman who presented with an extensive stroke with an unspecified cause. She had a concurrent genital infection with Mycoplasma hominis for an unknown duration. CONCLUSION: An association may exist between stroke and the immune response to Mycoplasma hominis infection.

Memory Clinics and Day Care Centers in Thessaloniki, Northern Greece: 30 Years of Clinical Practice and Experience.

Background: This review describes the diagnostic and interventional procedures conducted in two university memory clinics (established network of G. Papanikolaou Hospital: 1988-2017 and AHEPA hospital: 2017-today) and 2 day care centers (established network of DCCs: 2005-today) in North Greece and their contribution in the scientific field of dementia. The aims of this work are (1) to provide a diagnosis and treatment protocol established in the network of memory clinics and DCCs and (2) to present further research conducted in the aforementioned network during the last 30 years of clinical practice. Methods: The guidelines to set a protocol demand a series of actions as follows: (1) set the diagnosis criteria, neuropsychological assessment, laboratory examinations, and examination of neurophysiological, neuroimaging, cerebrospinal fluid, blood, and genetic markers; and (2) apply non-pharmacological interventions according to the needs and specialized psychosocial interventions of the patient to the caregivers of the patient. Results: In addition to the guidelines followed in memory clinics at the 1st and 3rd Department of Neurology and two DCCs, a database of patients, educational programs, and further participation in international research programs, including clinical trials, make our contribution in the dementia field strong. Conclusion: In the current paper, we provide useful guidelines on how major and minor neurocognitive disorders are being treated in Thessaloniki, Greece, describing successful practices which have been adapted in the last 30 years.

A Novel Connectome-Based Electrophysiological Study of Subjective Cognitive Decline Related to Alzheimer's Disease by Using Resting-State High-Density EEG EGI GES 300.

Aim: To investigate for the first time the brain network in the Alzheimer's disease (AD) spectrum by implementing a high-density electroencephalography (HD-EEG - EGI GES 300) study with 256 channels in order to seek if the brain connectome can be effectively used to distinguish cognitive impairment in preclinical stages. Methods: Twenty participants with AD, 30 with mild cognitive impairment (MCI), 20 with subjective cognitive decline (SCD) and 22 healthy controls (HC) were examined with a detailed neuropsychological battery and 10 min resting state HD-EEG. We extracted correlation matrices by using Pearson correlation coefficients for each subject and constructed weighted undirected networks for calculating clustering coefficient (CC), strength (S) and betweenness centrality (BC) at global (256 electrodes) and local levels (29 parietal electrodes). Results: One-way ANOVA presented a statistically significant difference among the four groups at local level in CC [F (3, 88) = 4.76, p = 0.004] and S [F (3, 88) = 4.69, p = 0.004]. However, no statistically significant difference was found at a global level. According to the independent sample t-test, local CC was higher for HC [M (SD) = 0.79 (0.07)] compared with SCD [M (SD) = 0.72 (0.09)]; t (40) = 2.39, p = 0.02, MCI [M (SD) = 0.71 (0.09)]; t (50) = 0.41, p = 0.004 and AD [M (SD) = 0.68 (0.11)]; t (40) = 3.62, p = 0.001 as well, while BC showed an increase at a local level but a decrease at a global level as the disease progresses. These findings provide evidence that disruptions in brain networks in parietal organization may potentially represent a key factor in the ability to distinguish people at early stages of the AD continuum. Conclusions: The above findings reveal a dynamically disrupted network organization of preclinical stages, showing that SCD exhibits network disorganization withintermediate values between MCI and HC. Additionally, these pieces of evidence provide information on the usefulness of the 256 HD-EEG in network construction.

Can a Novel High-Density EEG Approach Disentangle the Differences of Visual Event Related Potential (N170), Elicited by Negative Facial Stimuli, in People with Subjective Cognitive Impairment?

BACKGROUND: Studies on subjective cognitive impairment (SCI) and neural activation report controversial results. OBJECTIVE: To evaluate the ability to disentangle the differences of visual N170 ERP, generated by facial stimuli (Anger & Fear) as well as the cognitive deterioration of SCI, mild cognitive impairment (MCI), and Alzheimer's disease (AD) compared to healthy controls (HC). METHOD: 57 people took part in this study. Images corresponding to facial stimuli of "Anger" and "Fear" were presented to 12 HC, 14 SCI, 17 MCI and 14 AD participants. EEG data were recorded by using a HD-EEG HydroCel with 256 channels. RESULTS: Results showed that the amplitude of N170 can contribute in distinguishing the SCI group, since statistically significant differences were observed with the HC (p < 0.05) and the MCI group from HC (p < 0.001), as well as AD from HC (p = 0.05) during the processing of facial stimuli. Noticeable differences were also observed in the topographic distribution of the N170 amplitude, while localization analysis by using sLORETA images confirmed the activation of superior, middle-temporal, and frontal lobe brain regions. Finally, in the case of "Fear", SCI and HC demonstrated increased activation in the orbital and inferior frontal gyrus, respectively, MCI in the inferior temporal gyrus, and AD in the lingual gyrus. CONCLUSION: These preliminary findings suggest that the amplitude of N170 elicited after negative facial stimuli could be modulated by the decline related to pathological cognitive aging and can contribute in distinguishing HC from SCI, MCI, and AD.

International Ballroom Dancing Against Neurodegeneration: A Randomized Controlled Trial in Greek Community-Dwelling Elders With Mild Cognitive impairment.

BACKGROUND: Many studies have highlighted the positive effects of dance in people with neurodegenerative diseases. OBJECTIVES: To explore the effects of International Ballroom Dancing on cognitive function in elders with amnestic mild cognitive impairment (aMCI). METHODS: One-hundred twenty-nine elderly patients with aMCI diagnosis (mean age 66.8 ± 10.1 years) were randomly assigned into 2 groups: intervention group (IG, n = 66) and control group (CG, n = 63). The IG exercised systematically for 10 months, and both groups were submitted to extensive neuropsychological assessment prior and after the 10-month period. RESULTS: According to the independent sample t test at the follow-up, significant differences between groups were found in benefit of the IG while the CG showed worse performance in the majority of neuropsychological tests. According to the Student t test, better performance is detected in IG in contrast with CG, which had worse performance almost in all scales. CONCLUSION: Dance may be an important nonpharmacological approach that can benefit cognitive functions.

Brain source localization of MMN and P300 ERPs in mild cognitive impairment and Alzheimer's disease: a high-density EEG approach.

Alzheimer's disease is the most common neurodegenerative disease of Western societies, suggesting the need for early diagnosis, even in preclinical stages. In this vein, the localization of neuronal generators of event-related potential (ERP) components, that is, the mismatch negativity and the P300, based on high-density electroencephalogram data, was explored as a means to enhance their sensitivity as markers of preclinical Alzheimer's disease (AD). A 2-tone oddball experiment was conducted, involving 21 healthy elderly, 21 mild cognitive impairment, and 21 mild AD patients, while high-density electroencephalogram data were recorded. The results revealed longer latencies of both mismatch negativity and P300 and slower and far less accurate responses as neurodegeneration progressed. Standardized low-resolution electromagnetic tomography revealed that source differences between healthy and mild cognitive impairment and healthy and AD patients for both ERP components were present in the same Brodmann area independently of the ERP and the stage of cognitive decline. This finding indicates an early change of source activation related to cognitive performance and may be used to improve the diagnostic and prognostic value of ERPs.

Age-induced differences in brain neural activation elicited by visual emotional stimuli: A high-density EEG study.

Identifying the brain sources of neural activation during processing of emotional information remains a very challenging task. In this work, we investigated the response to different emotional stimuli and the effect of age on the neuronal activation. Two negative emotion conditions, i.e., 'anger' and 'fear' faces were presented to 22 adult female participants (11 young and 11 elderly) while acquiring high-density electroencephalogram (EEG) data of 256 channels. Brain source localization was utilized to study the modulations in the early N170 event-related-potential component. The results revealed alterations in the amplitude of N170 and the localization of areas with maximum neural activation. Furthermore, age-induced differences are shown in the topographic maps and the neural activation for both emotional stimuli. Overall, aging appeared to affect the limbic area and its implication to emotional processing. These findings can serve as a step toward the understanding of the way the brain functions and evolves with age which is a significant element in the design of assistive environments.

Cognitive MMN and P300 in mild cognitive impairment and Alzheimer's disease: A high density EEG-3D vector field tomography approach.

Precise preclinical detection of dementia for effective treatment and stage monitoring is of great importance. Miscellaneous types of biomarkers, e.g., biochemical, genetic, neuroimaging, and physiological, have been proposed to diagnose Alzheimer's disease (AD), the usual suspect behind manifested cognitive decline, and mild cognitive impairment (MCI), a neuropathology prior to AD that does not affect cognitive functions. Event related potential (ERP) methods constitute a non-invasive, inexpensive means of analysis and have been proposed as sensitive biomarkers of cognitive impairment; besides, various ERP components are strongly linked with working memory, attention, sensory processing and motor responses. In this study, an auditory oddball task is employed, to acquire high density electroencephalograhy recordings from healthy elderly controls, MCI and AD patients. The mismatch negativity (MMN) and P300 ERP components are then extracted and their relationship with neurodegeneration is examined. Then, the neural activation at these components is reconstructed using the 3D vector field tomography (3D-VFT) inverse solution. The results reveal a decline of both ERPs amplitude, and a statistically significant prolongation of their latency as cognitive impairment advances. For the MMN, higher brain activation is usually localized in the inferior frontal and superior temporal gyri in the controls. However, in AD, parietal sites exhibit strong activity. Stronger P300 generators are mostly found in the frontal lobe for the controls, but in AD they often shift to the temporal lobe. Reduction in inferior frontal source strength and the switch of the maximum intensity area to parietal and superior temporal sites suggest that these areas, especially the former, are of particular significance when neurodegenerative disorders are investigated. The modulation of MMN and P300 can serve to produce biomarkers of dementia and its progression, and brain imaging can further contribute to the diagnostic efficiency of ERPs.

Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial.

There is evidence to suggest the efficacy of Crocus (saffron) in the management of cognitive decline. This study examined the efficacy of Crocus in patients with amnesic and multi domain MCI (aMCImd). The participants included 17 patients on Crocus and 18 on a waiting list, who were examined with a short neuropsychological battery, MRI 3T, while some patients were examined via 256-channel electroencephalogram (HD-EEG) at baseline and after 12 months. The results showed that patients on Crocus had improved Mini-Mental State Examination scores (p = 0.015), while the control group deteriorated. Also, MRI, EEG, and ERP showed improvement in specific domains. This led us to conclude that Crocus is a good choice for management of aMCImd.

Brain source localization of MMN, P300 and N400: aging and gender differences.

The localization of neuronal generators during an ERP study, using a high-density electroencephalogram (HD-EEG) equipment was made on three Evoked Related Potential (ERP) components, i.e., the Mismatch Negativity (MMN), the P300 and the N400. Furthermore, the ERP characteristics, their field distribution and the area of their maximum field intensity were extracted and compared between young and elderly, as well as between females and males. A two tone oddball experiment was conducted, involving 27 young adults and 18 elderly, healthy and right handed, and HD-EEG data were acquired. These data were then subjected to auditory ERPs extraction and thorough statistical analysis. The derived experimental results revealed significant age-related differences to both the latencies and the amplitudes of the MMN and the P300 and the topographic distribution of the HD-EEG amplitudes. Additionally, a shift in the maximum intensities from frontal to temporal lobe with aging appeared in the case of the P300, whereas no effect was observed for the MMN component. No statistical significant differences (p>0.05) due to age was found in N400 characteristics. Finally, gender-related differences were significant in the response time of the subjects, finding males response faster. The level and the location of the maximum intensity of sources also differed between genders, especially in young subjects. These findings justify the enhanced potential of HD-EEG data to accurately reflect the age and gender dependencies at the three components of simple auditory ERPs and pave the way for the investigation of neurodegenerative pathologies, such as the Alzheimer's disease.

Five-year biomarker progression variability for Alzheimer's disease dementia prediction: Can a complex instrumental activities of daily living marker fill in the gaps?

INTRODUCTION: Biomarker progressions explain higher variability in cognitive decline than baseline values alone. This study examines progressions of established biomarkers along with a novel marker in a longitudinal cognitive decline. METHODS: A total of 215 subjects were used with a diagnosis of normal, mild cognitive impairment (MCI) or Alzheimer's disease (AD) at baseline. We calculated standardized biomarker progression rates and used them as predictors of outcome within 5 years. RESULTS: Early cognitive declines were more strongly explained by fluorodeoxyglucose-positron emission tomography, precuneus and medial temporal cortical thickness, and the complex instrumental activities of daily living (iADL) marker progressions. Using Cox proportional hazards model, we found that these progressions were a significant risk factor for conversion from both MCI to AD (adjusted hazard ratio 1.45; 95% confidence interval 1.20-1.93; P = 1.23 × 10(-5)) and cognitively normal to MCI (adjusted hazard ratio 1.76; 95% confidence interval 1.32-2.34; P = 1.55 × 10(-5)). DISCUSSION: Compared with standard biological biomarkers, complex functional iADL markers could also provide predictive information for cognitive decline during the presymptomatic stage. This has important implications for clinical trials focusing on prevention in asymptomatic individuals.