Male patient with mild cognitive impairment and extremely high P300 and Slow-wave latencies: a case report

We present a case of a 74-year-old Greek male who suffered from paraphasias, memory and orientation problems. The patient was assessed with neuropsychometric tests, auditory event-related potentials and cerebrospinal fluid proteins and was diagnosed with mild cognitive impairment. The emphasis on the case is on the unexplained high levels of P300 and Slow wave of the auditory event-related potentials

Inhibitory Control, Task/Rule Switching, and Cognitive Planning in Vascular Dementia: Are There Any Differences From Vascular Aging?

Recent studies have shown that patients diagnosed with Vascular Dementia (VaD) exhibit deficits in executive functions. According to “vascular hypothesis of cognitive aging,” community-dwelling older adults having risk factors for vascular disease development (RVD) may suffer from cognitive decline of the same type. The aim of the study was to assess the level of specific executive functions (EF) that have been revealed as most affected by vascular abnormalities, in older adults with incipient VaD and RVD. Subsequently specific ways of EF measuring could be suggested for more accurate diagnosis of early stage VaD. The study compared three adult groups (N = 60): (a) patients diagnosed with incipient VaD, according to DSM-5 criteria (n = 20); (b) community-dwelling older adults presenting cardiovascular risk factors (RVD; n = 20); (c) healthy young adult controls (n = 20). Three types of executive functions were examined: inhibitory control, cognitive flexibility as rule/task switching, and planning. The following D-KEFS subtests were administered for their evaluation: The ‘Color-Word Interference Test,’ the ‘Verbal Fluency Test,’ and the ‘Tower Test.’ Mixed-measures ANOVA, MANOVA, and one-way ANOVA as well as Scheffe post hoc test were applied to the data of the scores in each condition of each test. The results showed that VaD patients had significantly lower performance in test conditions requiring switching and planning, compared to RVD group and young controls. The specific deficits of VaD patients, compared to older adults presenting RVD according to multiple-group path analyses were: more uncorrected errors in inhibition, the use of semantic knowledge primarily instead of switching ability to switch between semantic categories, as well as a lower level of movement precision in planning

Usefulness of event-related potentials in the assessment of mild cognitive impairment

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine if changes in latencies and amplitudes of the major waves of Auditory Event-Related Potentials (AERP), correlate with memory status of patients with mild cognitive impairment (MCI) and conversion to Alzheimer's disease (AD).</p> <p>91 patients with MCI (mean ± SD age = 66.6 ± 5.4, MMSE score = 27.7) and 30 age-matched healthy control (AMHC) subjects (mean ± SD age = 68.9 ± 9.9) were studied. 54 patients were re-examined after an average period of 14(± 5.2) months. During this time period 5 patients converted to AD. Between-group differences in latency and amplitude of the major AERP waves (N200, P300 and Slow Wave) were determined. Within each group, correlation coefficients (CC) between these characteristics of the different AERP waves were calculated. Finally, for patients, CCs were determined among each AERP wave and their age and MMSE scores. Confirmatory factor analysis (CFA) was used to examine the underlying structure of waveforms both in the control and the patient groups.</p> <p>Results</p> <p>Latencies of all major AERP components were prolonged in patients compared to controls. Patients presented with significantly higher N200 amplitudes, but no significant differences were observed in P300 amplitudes. Significant differences between follow-up and baseline measurements were found for P300 latency (p = 0.009), N200 amplitude (p < 0.001) and P300 amplitude (p = 0.05). MMSE scores of patients did not correlate with latency or amplitude of the AERP components. Moreover, the establishment of a N200 latency cut-off value of 287 ms resulted in a sensitivity of 100% and a specificity of 91% in the prediction of MCI patients that converted to AD.</p> <p>Conclusion</p> <p>Although we were not able to establish significant correlations between latencies and amplitudes of N200, P300 and SW and the patients' performance in MMSE, which is a psychometric test for classifying patients suffering from MCI, our results point out that the disorganization of the AERP waveform in MCI patients is a potential basis upon which a neurophysiologic methodology for identifying and "staging" MCI can be sought. We also found that delayed N200 latency not only identifies memory changes better than the MMSE, but also may be a potential predictor of the MCI patients who convert to AD.</p

What Electrophysiology Tells Us About Alzheimer’s Disease::A Window into the Synchronization and Connectivity of Brain Neurons

Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer’s disease (AD), despite a surge in recent validated evidence. This Position Paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity reflecting thalamocortical and cortico-cortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies

Consensus Statement on Dementia Education and Training in Europe

OBJECTIVES: The aim of the current statement is to agree on: (1) what is the current situation with education and training on dementia in Europe; (2) what are the minimum educational requirements for professionals (neurologists, psychiatrists, primary care providers, nurses, biologists, neuroradiologists, etc.) regarding Alzheimer's disease and dementia, and (3) how to start a course of action for the future. DESIGN: In 2005, a simple questionnaire was sent to members of the European Alzheimer's Disease Consortium (EADC) concerning the education and training on dementia in their countries. Fourteen universities of the respective countries responded to this simple questionnaire. The answers varied, and the conclusion of this effort was that little was done concerning the training of students and health professionals on dementia. In 2008, another more structured and specified questionnaire was sent to professors in different universities of the same countries. RESULTS: The answers obtained were different from those of the previous questionnaire and demonstrated that it is very difficult to know about training and education in the field of dementia in every European country. CONCLUSION: From the data collected, it seems that although in the recent past little had been done concerning training on dementia, nowadays training has been developed in most European countries, and relevant educational projects exist both for medical students and doctors during their specialty training. Our main purpose is to develop training material or develop specific courses to improve the professional knowledge about dementia so that best medical and non-medical practice is implemented

Behavioral and Cognitive Improvement Induced by Novel Imidazoline I2 Receptor Ligands in Female SAMP8 Mice

As populations increase their life expectancy, age-related neurodegenerative disorders such as Alzheimer's disease have become more common. I2-Imidazoline receptors (I2-IR) are widely distributed in the central nervous system, and dysregulation of I2-IR in patients with neurodegenerative diseases has been reported, suggesting their implication in cognitive impairment. This evidence indicates that high-affinity selective I2-IR ligands potentially contribute to the delay of neurodegeneration. In vivo studies in the female senescence accelerated mouse-prone 8 mice have shown that treatment with I2-IR ligands, MCR5 and MCR9, produce beneficial effects in behavior and cognition. Changes in molecular pathways implicated in oxidative stress, inflammation, synaptic plasticity, and apoptotic cell death were also studied. Furthermore, treatments with these I2-IR ligands diminished the amyloid precursor protein processing pathway and increased Aβ degrading enzymes in the hippocampus of SAMP8 mice. These results collectively demonstrate the neuroprotective role of these new I2-IR ligands in a mouse model of brain aging through specific pathways and suggest their potential as therapeutic agents in brain disorders and age-related neurodegenerative diseases. Keywords Imidazoline I2 receptors (2-imidazolin-4-yl)phosphonates Behavior Cognition Neurodegeneration Neuroprotection Agin

Assessment of apoptosis with cerebrospinal fluid proteins and event related potentials in patients with mild cognitive impairment

Patients with mild cognitive impairment (MCI) have memory problems bigger than those expected due to aging, but do not experience any impairment in any other cognitive functions such as thought, cognition and attention or difficulties in daily life activities. Apoptosis is a normal procedure, essential for the development of multicellular organisms, and is believed to play a role in MCI pathogenesis. The aim of this study was the examination of the cognitive function of MCI patients, the assessment of the apoptotic process, using measurements of cerebrospinal fluid proteins levels, and the finding of potential correlations between possible mechanisms involved in MCI and Alzheimer’s disease (AD). The study group consisted of a total of one hundred and twenty one (121) subjects of which ninety one (91) patients with MCI and thirty (30) healthy controls. The mean±SD age of the patient group was 67.1±6.9 years (range 46-83 years) and of the control subjects 68.7±9.9 years (range 49-90 years). The patient group consisted of 35 males and 56 females and the control group of 15 males and 15 females. The two groups were matched for age (t-test, t=-0.96, p=0.34) and gender (χ²=1.24, p=0.27). All subjects underwent: a) An examination with auditory event-related potentials (AERPs). The exam was performed in the Clinical Neurophysiology Department of the 3rd Neurological Clinic of the Aristotle University of Thessaloniki in the hospital “G. Papanikolaou”. From the 91 patients, who underwent an exam with AERPs, 43 were re-examined after an average period time of 12 months (range 7-17 months) and 11 after an average time of 22 months (18-26 months) from baseline. 22 patients underwent a third examination after an average time of 23 (±3) months from baseline. b) The MMSE neuropsychometric test. A clinical evaluation of the current disease situation was performed in MCI patients. Furthermore a lumbar puncture was performed in 54 patients and the levels of the CSF proteins: beta amyloid₁₋₄₂, tau, Bcl-2, Fas, Fas-L and cytochrome c were determined. In 20 of these patients a second sample of CSF was taken after an average period of 11.5 months. During the study period, five patients developed AD. A statistical analysis was performed in the results of all the parameters in control subjects and MCI patients. The results in the control subjects reveal a significant increase with age of the latencies of the AERP waves N200, P300 and SW. Furthermore the latencies of all waves correlate significantly with each other. Therefore it seems that each one is dependent upon the other. There is a highly significant association between P300-N200 latency difference and P300, whereas similar correlation exists between the difference between SW and P300 latencies and the difference between the latencies of SW and N200. The difference between SW and P300 latencies is highly correlated with SW wave latency and associated with P300 latency. From the statistical analysis of the results in the MCI patients, similar correlations as those of the control group were observed, except for the correlations between latency differences SW-N200 and SW-P300 and SW-P300 with latencies of P300 and SW, which do not exist in MCI patients. Moreover, no significant correlation was observed in MCI patients between their performance in MMSE and the characteristics of the three AERP waves. A significant increase was observed in N200 latency in the baseline examination of the MCI patients that later developed AD. The use of a cut-off value of 300 ms resulted in a high sensitivity and specificity in the discrimination between MCI and AD patients. Therefore, there are indications that N200 latency may serve as an accurate neurophysiological diagnostic marker for the early diagnosis of AD. Moreover a significant correlation was observed between beta-amyloid levels and N200 latency both in the baseline and follow up exam. The combination of these parameters (cut-off values >287 ms for N200 latency and 287 ms για το χρόνο εμφάνισης του Ν200 και <500 pg/ml για το β-αμυλοειδές) έχει τη μέγιστη διαγνωστική ακρίβεια (100% ευαισθησία, 100% ειδικότητα) όσον αφορά την εξέλιξη των ασθενών με ΗΝΔ σε ΝΑ. Όσον αφορά τις πρωτεΐνες του ΕΝΥ οι οποίες εξετάσθηκαν, βρέθηκε πολύ μεγάλη αύξηση των επιπέδων της τ-πρωτεΐνης (τετραπλασιασμός) της Fas-L και του κυτοχρώματος c (τριπλασιασμός) σε αυτούς τους λίγους ασθενείς στους οποίους η ΗΝΔ εξελίχθηκε σε ΝΑ, γεγονός που ενισχύει την άποψη ότι η απόπτωση παίζει ρόλο στη ΝΑ. Αντίθετα στους ασθενείς με ΗΝΔ που η νόσος δεν εξελίχθηκε, παρατηρείται αύξηση μόνο στην τ-πρωτεΐνη. Εκτός από τις τιμές του λανθάνοντα χρόνου εμφάνισης N200L, η αύξηση των τιμών του κυτοχρώματος c μεταξύ των περιόδων εξέτασης, έχει επίσης μεγάλη ευαισθησία και ειδικότητα στο διαχωρισμό ασθενών με ΗΝΔ στους οποίους η νόσος εξελίχθηκε σε ΝΑ και αυτών που η ΗΝΔ παρέμεινε σταθερή. Τα αποτελέσματα της έρευνας, κατά την άποψή μας, υποδηλώνουν ότι η ΗΝΔ και η ΝΑ είναι δυο διαφορετικές και με πολλούς τρόπους μη σχετικές κλινικές οντότητες. Η ΗΝΔ μπορεί να λειτουργεί ως υποστρωματικός παράγοντας για την μετέπειτα εξέλιξη σε ΝΑ, αλλά δεν αποτελεί αιτιολογικό παράγοντα της νόσου. Επίσης οι συσχετίσεις που παρατηρήθηκαν μεταξύ των επιπέδων του κυτοχρώματος c στο ΕΝΥ και του ύψους του επάρματος Ν200, όπως επίσης και των επιπέδων του β-αμυλοειδούς και του λανθάνοντα χρόνου εμφάνισης του Ν200 (που υποδηλώνει ότι ο λανθάνων χρόνος εμφάνισης και το ύψος του Ν200 επηρεάζονται από τις αποπτωτικές διαδικασίες που λαμβάνουν χώρα κατά την ΗΝΔ) καταδεικνύει ότι η ΗΝΔ προσβάλλει κατά πάσα πιθανότητα τα κύτταρα του εγκεφαλικού φλοιού που συμμετέχουν στην παράπλευρη αναστολή

Correlates of Functional Impairment in Patients with the Behavioral Variant of Frontotemporal Dementia: A PRISMA-Compliant Systematic Review

The behavioral variant of frontotemporal dementia (bvFTD) has a devastating effect on multiple domains of daily living. The purpose of this PRISMA-compliant systematic review is to summarize the most important factors associated with functional impairment in this clinical group by critically analyzing the existing literature spanning the period from 2000 to 2023. To be included in the review, a study had to investigate any kind of correlates of functional status in bvFTD patients, using a previously validated instrument of functional assessment. Out of 40 articles assessed for eligibility, 18 met the inclusion criteria. The anatomical pattern of cerebral atrophy at baseline appeared to be the strongest predictor of the rate of functional decline over time, with the frontal-dominant anatomical subtype being associated with a faster rate of functional impairment. Additionally, executive dysfunction as well as apathy appeared to contribute significantly to functional disability in bvFTD patients. A comparative examination of bvFTD in relation to other clinical subtypes of FTD and other types of dementia in general suggests that it is the predominant atrophy of the frontal lobes along with the subsequent unique combination of cognitive and neuropsychiatric manifestations that account for the pronounced functional limitations observed in these individuals, even from the early stages of the disease