1. J Neurovirol. 2020 Dec;26(6):870-879. doi: 10.1007/s13365-020-00904-6. Epub 2020 
Sep 10.

Direct antivirals and cognitive impairment in hepatitis C: a 
clinical-neurophysiologic study.

Vaghi G(1), Gori B(2), Strigaro G(3), Burlone M(1), Minisini R(1), Barbaglia 
MN(1), Brigatti E(2), Varrasi C(2), Pirisi M(1), Cantello R(2).

Author information:
(1)Internal Medicine Department of Translational Medicine, University of 
Piemonte Orientale, Novara, Italy.
(2)Neurology Unit Department of Translational Medicine, University of Piemonte 
Orientale, Novara, Italy.
(3)Neurology Unit Department of Translational Medicine, University of Piemonte 
Orientale, Novara, Italy. gionata.strigaro@gmail.com.

Cognition was assessed in hepatitis C virus (HCV) patients, who did not meet the 
criteria for a minimal hepatic encephalopathy. Their liver function was 
compensated. We then disentangled potential cognitive changes associated with a 
sustained virologic response at 12 weeks (SVR-12), following treatment with 
direct antiviral agents (DAAs). We studied 23 selected HCV patients with a 
battery of standard neuropsychological tests, and with recordings of the P300 
wave, a cerebral potential of "cognitive" significance. There was a baseline 
evaluation (T0) and a second one 6 months later (T1). We had 2 control groups of 
comparable age and sex, i.e., 15 patients suffering from non-alcoholic fatty 
liver disease (NAFLD) and 15 healthy subjects. At T0, we detected a significant 
(p < 0.05) cognitive impairment in the HCV group, which involved episodic and 
working memory, attention, visuospatial and verbal abilities, executive 
functions, and logic reasoning. The P300 latency was significantly (p < 0.05) 
delayed in the group. At T1, we observed some significant (p < 0.05) HCV 
recovery in given test domains, e.g., memory, executive functions, and 
reasoning. Accordingly, the P300 latency shortened significantly (p < 0.05). HCV 
patients exhibited subtle cognitive defects, somehow independent of their liver 
condition, possibly linked to direct or indirect brain involvement by the virus. 
These defects partly recovered following the SVR-12, as achieved through DAAs. 
The P300 wave was a valid neurophysiologic counterpart of these changes. DAAs 
can have a role in the early preservation of cognition in HCVs.

DOI: 10.1007/s13365-020-00904-6
PMCID: PMC7716927
PMID: 32910431 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that they have no conflicts 
of interest.


2. BMJ Open. 2020 Oct 16;10(10):e037307. doi: 10.1136/bmjopen-2020-037307.

Effect of 12-week pulmonary rehabilitation on cognitive function in patients 
with stable chronic obstructive pulmonary disease: study protocol for a 
single-center randomised controlled trial.

Duan H(#)(1), Li P(#)(2), Wang Z(3), Chen H(2), Wang T(2), Wu W(2), Liu X(4).

Author information:
(1)School of Rehabilitation Science, Shanghai University of Traditional Chinese 
Medicine, Shanghai, China.
(2)Department of Sports Medicine, Shanghai University of Sport, Shanghai, China.
(3)Department of Respiratory Medicine, Shanghai University of Traditional 
Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese Medicine and 
Western Medicine, Shanghai, China.
(4)School of Rehabilitation Science, Shanghai University of Traditional Chinese 
Medicine, Shanghai, China hzhp403@126.com.
(#)Contributed equally

INTRODUCTION: Cognitive impairment, an important complication in patients with 
chronic obstructive pulmonary disease (COPD), seriously affects self-management 
of the disease and quality of life (QoL). As an exercise-based intervention 
programme, pulmonary rehabilitation (PR)-especially aerobic exercise (mainly 
mind-body exercise) and resistance exercise (RE)-has been proposed for its 
potential effectiveness in improving cognitive function. However, there is still 
a lack of strong evidence for PR's effectiveness. In this study, we expect to 
clarify the effects of pulmonary-based Qigong exercise and elastic band-based RE 
on cognitive function in patients with COPD and to fill in the relevant evidence 
blanks.
METHODS AND ANALYSIS: This study is a single-centre randomised controlled trial 
with assessor and data analyst blinding. We will recruit 108 participants with 
stable COPD starting on 23 December 2019, and randomly allocate them into the 
pulmonary-based Qigong exercise group, elastic band-based RE group, 
pulmonary-based Qigong exercise and elastic band-based RE combined group, or 
control group at a 1:1:1:1 ratio. Participants in intervention groups will 
perform 30 min of exercise two times per day, 5 days a week, for 12 weeks. The 
primary outcome will be the global cognitive function as assessed by the 
Montreal Cognitive Assessment and auditory event-related potential P300. 
Secondary outcomes will include the specific cognitive domains-attention, 
memory, executive function, verbal fluency and mental-processing speed; 
psychological functions and QoL. Exploratory outcomes will include grey matter 
volume and levels of inflammatory mediators. Outcomes will be measured before 
and after the interventions.
ETHICS AND DISSEMINATION: Ethics approval has been granted by the Ethics 
Committee of Yue-Yang Integrative Medicine Hospital, an affiliate of Shanghai 
University of Traditional Chinese Medicine, Shanghai, China (Grant No. 
2019-141). Written informed consent will be obtained from each participant 
before any procedures are performed. The findings will be published in 
peer-reviewed journals and presented at academic conferences.
TRIAL REGISTRATION NUMBER: ChiCTR1900026869; pre-results.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No 
commercial re-use. See rights and permissions. Published by BMJ.

DOI: 10.1136/bmjopen-2020-037307
PMCID: PMC7569932
PMID: 33067278 [Indexed for MEDLINE]

Conflict of interest statement: Competing interests: None declared.


3. Monaldi Arch Chest Dis. 2019 May 24;89(2). doi: 10.4081/monaldi.2019.1039.

Identification of subclinical cognitive impairment in chronic obstructive 
pulmonary disease using auditory P300 event related potential.

Krishnamurthy S(1), Sivagnaname Y, Gumallapu GC.

Author information:
(1)Department of Physiology, Sri Manakula Vinayagar Medical College and 
Hospital, Puducherry. nsivagnaname@yahoo.com.

Adequate cognitive functioning in chronic obstructive pulmonary disease (COPD) 
patients is essential to understand the nature of the disease, adherence to 
treatment, and for leading a better quality of life. While cognitive impairment 
in severe forms of COPD have been well documented, identification of subclinical 
cognitive impairment in stable COPD patients remains crucial for planning 
prevention strategies. Hence the present study aimed to study and compare the 
cognitive function between the COPD patients, and normal individuals. The 
cognitive function was assessed in 42 stable COPD patients and 42 normal 
individuals with Mini Mental State Examination (MMSE), and auditory P300 event 
related potentials. Baseline characteristics and the cognitive parameters were 
compared between the COPD patients and the normal individuals; a p<0.05 was 
considered statistically significant. The latency of the P300 waves was 
significantly (p<0.05) prolonged (304.27±20.73 in COPD, 291.11± 24.53 in normal 
individuals), and the amplitude (4.36±1.56 in COPD, 5.46±3.12 in normal 
individuals) was significantly reduced in the COPD patients compared to the 
normal individuals. MMSE scores were also significantly (p<0.001) different 
between the COPD patients (26.97±0.89), and the normal individuals (27.80±0.83). 
Cognition may be affected even at the earlier stages of the disease among the 
COPD patients, as evident by changes in the P300 values. Auditory P300 event 
related potential may be used as an adjunct to the routine MMSE examination, as 
it serves as an effective tool in identifying the cognitive impairment in 
different stages of COPD. This may help the patients to adopt prevention 
strategies that help to avoid adverse effects on cognition in future.

DOI: 10.4081/monaldi.2019.1039
PMID: 31148604 [Indexed for MEDLINE]


4. Front Aging Neurosci. 2019 May 3;11:104. doi: 10.3389/fnagi.2019.00104. 
eCollection 2019.

P300, Gray Matter Volume and Individual Characteristics Correlates in Healthy 
Elderly.

Pergher V(1), Tournoy J(2), Schoenmakers B(3), Van Hulle MM(1).

Author information:
(1)Laboratory for Neuro- and Psychophysiology, Department of Neurosciences, KU 
Leuven - University of Leuven, Leuven, Belgium.
(2)Department of Chronic Disease, Metabolism and Ageing, KU Leuven - University 
of Leuven, Leuven, Belgium.
(3)Academic Centre of General Practice, KU Leuven - University of Leuven, 
Leuven, Belgium.

We investigated whether P300-ERP and cognitive test performance differ for age, 
sex, and education in two groups of healthy elderly, and verified whether any 
correlations exist between P300 amplitude and latency and gray matter volume 
using whole brain voxel-by-voxel-based mapping, controlling for age, education, 
sex and Total Intracranial Volume (TIV). We used 32 channel 
electroencephalograms (EEG) to record the P300 responses and 3T Magnetic 
Resonance Imaging (MRI) to determine gray matter volume. We recruited 36 
native-Dutch speaking healthy older subjects, equally divided in two sub-groups 
of 52-64 and 65-76 years old, administered a battery of cognitive tests and 
recorded their demographics, EEGs and task performance; additionally, 16 adults 
from the second sub-group underwent an MRI scan. We found significant 
differences between age groups in their cognitive tests performance, P300 
amplitudes for the frontal and parietal electrodes for the most difficult task, 
and P300 latencies for frontal, central and parietal electrodes for all three 
tasks difficulty levels. Interesting, sex and education affected cognitive and 
P300 results. Higher education was related to higher accuracy, and P300 
amplitudes and shorter latencies. Moreover, females exhibited higher P300 
amplitudes and shorter latencies, and better cognitive tasks performance 
compared to males. Additionally, for the 16 adults underwent to MRI scan, we 
found positive correlations between P300 characteristics in frontal, central and 
parietal areas and gray matter volume, controlling for demographic variables and 
TIV, but also showing that age, sex, and education correlate with gray matter 
volume. These findings provide support that age, sex, and education affect an 
individual's cognitive, neurophysiological and structural characteristics, and 
therefore motivate the need to further investigate these in relation to P300 
responses and gray matter volume in healthy elderly.

DOI: 10.3389/fnagi.2019.00104
PMCID: PMC6510164
PMID: 31130855


5. Cogn Neurodyn. 2018 Aug;12(4):385-390. doi: 10.1007/s11571-018-9482-4. Epub 2018 
Mar 2.

The effect of nasal polyposis related nasal obstruction on cognitive functions.

Arslan F(1), Tasdemir S(2), Durmaz A(3), Tosun F(3).

Author information:
(1)Department of Otolaryngology, Head and Neck Surgery, Beytepe Murat Erdi Eker 
State Hospital, Ankara, Turkey.
(2)Department of Neurology, Beytepe Murat Erdi Eker State Hospital, Ankara, 
Turkey.
(3)3Department of Otolaryngology, Head and Neck Surgery, Gulhane Medical School, 
Ankara, Turkey.

Chronic rhinosinusitis with nasal polyposis is a chronic inflammatory disease of 
the respiratory mucosa of the nasal cavity and paranasal sinuses. The aim of 
this study was investigate the effect of nasal obstruction related to chronic 
rhinosinusitis with nasal polyposis on cognitive functions. Patients with 
chronic rhinosinusitis with nasal polyposis causing bilateral total or near 
total nasal obstruction were enrolled in the study. Symptoms of nasal 
congestion, loss of smell, postnasal drip, headaches, snoring, concentration 
difficulties and blunted affect were evaluated by Visual Analog Scale. Brief 
symptom inventory test, Stroop test, visual aural digit span, serial digit 
learning test and P300 test were used to evaluate cognitive functions. Three 
months after treatment, the tests done before surgery were repeated and the 
results were compared. A total of 30 patients were included in the study. On the 
Visual Analog Scale, all symptoms showed significant postoperative improvement 
in all patients (p < 0.001 for all symptoms). Preoperative nasal congestion 
accompanied with impaired concentration were detected in 27 patients (90%), and 
these symptoms recovered in all these patients after treatment (p = 0.035) 
(correlation coefficient 0.4). Only 22 patients completed the neuropsychological 
tests. The mean preoperative Stroop test (23.16 ± 5.30), visual aural digit span 
test (24.68 ± 3.52), and serial digit learning test (16.18 ± 5.35) scores were 
showed significant improvement compared with mean postoperative Stroop test 
(21.12 ± 5.69), visual aural digit span test (26.45 ± 2.98), and serial digit 
learning test (19.31 ± 4.47) scores (p = 0.047, p = 0.022, p = 0.005 
respectively). The postoperative P300 latency values improved in 19 (63%) 
patients. The preoperative and postoperative latency values for P300 showed a 
significant difference (p = 0.029), whereas the preoperative and postoperative 
amplitude values for P300 did not differ (p = 0.096). In conclusion, the results 
of this study indicate that chronic rhinosinusitis with nasal polyposis (CRSwNP) 
has negative effects on cognitive functions, such as the ability to focus and 
maintain concentration. These cognitive functions improve after the patients 
undergo endoscopic sinus surgery to treat their CRSwNP.

DOI: 10.1007/s11571-018-9482-4
PMCID: PMC6048009
PMID: 30137875

Conflict of interest statement: Compliance with ethical standardsNo conflict of 
interests.The study began after the approval of the local ethics committee was 
obtained.


6. Asia Pac Allergy. 2018 Jul 18;8(3):e27. doi: 10.5415/apallergy.2018.8.e27. 
eCollection 2018 Jul.

Electrophysiological assessment of the concentration and attention in patient 
with nasal polyposis.

Ehi Y(1), Ozlece HK(2).

Author information:
(1)Department of Neurology, Kafkas University Medical School, Kars, Turkey.
(2)Department of Neurology, Acibadem Kayseri Hospital, Kayseri, Turkey.

BACKGROUND: Nasal polyposis is a chronic disease presenting with nasal 
obstruction as the most frequent complaint. It has been documented that nasal 
polyposis results in deterioration of quality of life and disturbances of sleep. 
However, remarkable consequences of nasal polyposis such as psychological and 
cognitive outcomes are relatively poorly studied.
OBJECTIVE: The aim of the present study was to evaluate whether there is an 
impairment of concentration and attention in nasal polyposis patients due to 
hypoxia caused by nasal obstruction.
METHODS: This cross-sectional, case-control study was carried out on 30 male 
patients with nasal polyps and 30 healthy subjects serving as controls. 
Participant ages were 41.6 ± 10.2 years in the nasal polyps group and 41.3 ± 6.2 
in the control group. All participants underwent systemic, neurological, and 
otorhinolaryngological examinations together with routine hematological and 
biochemical tests. Patients with nasal polyposis had bilateral complete 
obstruction of nasal cavity. P300 component of electroencephalography-derived 
event related potentials were used to monitor concentration and attention. Nasal 
polyposis and control groups were compared in terms of amplitude and latency of 
P300.
RESULTS: There were significant differences between control and nasal polyposis 
groups in terms of latency of P300 (p < 0.001). Nasal polyposis patient 
latencies in P300 were longer than controls (345.8 ± 16.6 msec, 309.3 ± 16.6 
msec, respectively). However, there were no significant differences between 
control and nasal polyposis groups in terms of amplitude of P300 (p > 0.05).
CONCLUSION: Results of the current study indicate that hypoxia due to complete 
nasal obstruction may result in impairment of attention and concentration in 
nasal polyposis patients. Assessment of patients with P300 latency subcomponent 
can be a useful diagnostic tool to detect cognitive and psychological 
consequences.

DOI: 10.5415/apallergy.2018.8.e27
PMCID: PMC6073176
PMID: 30079305


7. Brain Behav. 2018 Jan 31;8(3):e00918. doi: 10.1002/brb3.918. eCollection 2018 
Mar.

The characteristics of cognitive impairment in subjective chronic tinnitus.

Wang Y(1)(2)(3), Zhang JN(4), Hu W(5), Li JJ(6), Zhou JX(1)(2), Zhang JP(3), Shi 
GF(3), He P(3), Li ZW(3), Li M(4).

Author information:
(1)Yunnan University, University of Traditional Chinese Medicine Kunming China.
(2)Otolaryngological Department Yunnan Province Traditional Chinese Medicine 
Hospital of Yunnan University of Traditional Chinese Medicine Kunming China.
(3)Department of Neurology Wuxi People's Hospital of Nanjing Medical University 
Wuxi China.
(4)Department of Otolaryngology Yueyang Hospital of Integrated Traditional 
Chinese and Western Medicine Shanghai China.
(5)Department of Neurology Taihe Hospital Affiliated to Hubei University of 
Medicine Shiyan China.
(6)Department of Integrative Medicine Shanghai Children's Medical Center 
Shanghai Jiaotong University School of Medicine Shanghai China.

INTRODUCTION: Subjective chronic tinnitus is a common medical syndrome with a 
high frequency of cognitive impairment; however, the characteristics of 
cognitive impairment in chronic tinnitus are poorly understood. Investigating 
the scope of cognitive impairment across the severity spectrum of tinnitus 
patients may shed light on the issue.
METHODS: A consecutive series of 207 subjective chronic tinnitus patients were 
classified into mild tinnitus group (n = 95) and severe tinnitus group (n = 112) 
by THI score (the cutoff THI scores were 37/38). These patients were assessed 
using the Cognitive Abilities Screening Instrument (CASI) and P300 event-related 
potential.
RESULTS: Although pure tone averages were not different between mild or severe 
tinnitus patients, severe tinnitus patients scored lower on the CASI assessment 
as well as almost all subdomains of CASI, particularly in items such as 
"short-term memory," "concentration or mental manipulation," "orientation," 
"abstraction and judgment," "language abilities," and "visual construction." 
Furthermore, compared to mild tinnitus patients, severe tinnitus patients 
exhibited longer N2 and P3 latencies. Finally, a correlation analysis revealed 
that tinnitus severity was negatively correlated with CASI score and positively 
correlated with N2 and P3 latencies.
CONCLUSIONS: This study reveals that tinnitus patients on the severe end of the 
spectrum may be at risk for serious cognitive deficits, which may not be a 
secondary response to disease manifestations but a primary feature of the 
underlying disease.

DOI: 10.1002/brb3.918
PMCID: PMC5840442
PMID: 29541537 [Indexed for MEDLINE]


8. Int J Neurosci. 2017 Jul;127(7):592-600. doi: 10.1080/00207454.2016.1216415. 
Epub 2016 Aug 30.

Immediate memory and electrophysiologic effects of prefrontal cortex 
transcranial direct current stimulation on neurotypical individuals and 
individuals with chronic traumatic brain injury: a pilot study.

O'Neil-Pirozzi TM(1), Doruk D(2), Thomson JM(3), Fregni F(4).

Author information:
(1)a Department of Communication Sciences and Disorders , Northeastern 
University , Boston , MA , USA.
(2)b Department of Physical Medicine and Rehabilitation , Spaulding 
Rehabilitation Hospital/Harvard Medical School , Charlestown , MA , USA.
(3)c Labortory of Neuromodulation , Spaulding Rehabilitation Hospital/Harvard 
Medical School , Charlestown , MA , USA.
(4)d Developmental Psychology, Cognitive Psychology, Western Bank , The 
University of Sheffield , Sheffield , United Kingdom.

Purpose/aim: Memory impairment post-TBI is common, frequently persistent, and 
functionally debilitating. The purposes of this pilot study were to assess and 
to compare immediate behavioral auditory working memory and electrophysiologic 
effects of three different, randomized, conditions of left dorsolateral 
prefrontal cortex (LDLPFC) transcranial direct current stimulation (tDCS) 
applied to four neurotypical adults and four adults with chronic traumatic brain 
injury (TBI).
MATERIALS/METHODS: Pre- and post-anodal, cathodal, and sham tDCS auditory memory 
performance, auditory event-related potentials (P300 amplitude and latency) and 
power of alpha and theta EEG bands were measured across individuals in each 
group.
RESULTS: Post-anodal tDCS only, the neurotypical and TBI groups both 
demonstrated significantly improved immediate auditory memory function. Also 
post-anodal tDCS, the TBI group demonstrated significantly increased P300 
amplitude versus post-sham tDCS. The neurotypical group demonstrated no pre- 
post-tDCS electrophysiologic changes across conditions.
CONCLUSIONS: These findings are consistent with findings of other studies of 
immediate tDCS effects on other types of memory in neurotypical individuals and 
in individuals with Parkinson's disease, Alzheimer's disease and stroke and 
suggest that individuals with memory impairments second to chronic TBI may 
benefit from LDLPFC anodal tDCS. Pairing tDCS with traditional behavioral memory 
interventions may facilitate TBI rehabilitation outcomes and warrants continued 
investigation.

DOI: 10.1080/00207454.2016.1216415
PMID: 27453334 [Indexed for MEDLINE]


9. Biomed Res. 2017;38(6):371-374. doi: 10.2220/biomedres.38.371.

Cognitive impairment with interferon treatment in patients with chronic 
hepatitis C.

Tanaka H, Sasaki H.

Interferon (IFN) has various side effects, including psychiatric symptoms. 
Event-related potentials are used as an electrophysiologic index of cognitive 
disorders. Auditory event-related potentials (P300) are often used in conditions 
in which cognitive ability is affected. In this study, we evaluated the 
association between P300, used to assess cognitive impairment, and 
neuropsychological side effects of IFN treatment in patients with chronic 
hepatitis C. Subjects were 20 patients with chronic hepatitis C; 13 patients 
were treated with peg IFN-α2b and ribavirin (riba group), and 7 patients were 
treated with peg IFN-α2a (alone group). P300 was performed on all patients 
before treatment and after 1 week, 4 weeks, 2 months, and 3 months of treatment. 
In addition, 10 patients of them completed the self-rating depression scale 
(SDS). P300 latency was significantly prolonged at all points of measurement 
during IFN treatment. No correlation between the change of SDS score and the 
change rate of P300 latency was shown. Six patients with neuropsychological 
symptom had a significantly increased change rate of P300 latency compared with 
patients without neuropsychological symptoms (P < 0.05). Based on P300 findings, 
this study suggests that patients with chronic hepatitis C treated with IFN may 
experience significant cognitive impairment.

DOI: 10.2220/biomedres.38.371
PMID: 29225215 [Indexed for MEDLINE]


10. Med Arch. 2016 Dec;70(6):453-456. doi: 10.5455/medarh.2016.70.453-456.

P300 Wave Changes in Patients with Parkinson's Disease.

Tokic K(1), Titlic M(2), Beganovic-Petrovic A(3), Suljic E(3), Romac R(4), Silic 
S(4).

Author information:
(1)School of Medicine, University of Split, Split, Croatia.
(2)School of Medicine, University of Split, Split, Croatia; Department of 
Neurology, University Hospital Split, Split, Croatia.
(3)Department of Neurology, Clinical Center of Sarajevo University, Sarajevo, 
Bosnia and Herzegovina.
(4)Department of Neurology, University Hospital Split, Split, Croatia.

INTRODUCTION: Parkinson's disease (PD) is chronic progressive neurodegenerative 
disease. In patients with Parkinson's disease among other symptoms occur 
cognitive dysfunctions, which can be shown by P300 wave changes.
AIM: The aim of this study was to demonstrate that patients with Parkinson's 
disease have reduced amplitude and prolonged latency, longer than 300 ± 10 ms.
MATERIAL AND METHODS: The study included 21 patient suffering from Parkinson's 
disease. After reviewing the medical records and analyzes the inclusion and 
exclusion criteria, patients were subjected to the same procedure examining 
auditory cognitive potentials (P300 wave) and the results were analyzed and 
compared to reference value for healthy population.
RESULTS: We have shown that patients with Parkinson's disease have prolonged 
P300 targeted and frequent stimulus latency compared to reference value for 
healthy population. From 21 patient 18 had a pathological P300 target stimulus 
amplitude, and even 20 patients had pathological P300 frequent stimulus 
amplitude.
CONCLUSION: People with Parkinson's disease have altered P300 which indicates 
the presence of cognitive dysfunction in these patients.

DOI: 10.5455/medarh.2016.70.453-456
PMCID: PMC5292223
PMID: 28210020 [Indexed for MEDLINE]


11. Lung India. 2013 Jan;30(1):5-11. doi: 10.4103/0970-2113.106119.

A comparison of cognitive functions in non-hypoxemic chronic obstructive 
pulmonary disease (COPD) patients and age-matched healthy volunteers using 
mini-mental state examination questionnaire and event-related potential, P300 
analysis.

Gupta PP(1), Sood S, Atreja A, Agarwal D.

Author information:
(1)Department of Respiratory Medicine, Postgraduate Institute of Medical 
Sciences, Pt. B D Sharma University of Health Sciences, Rohtak, India.

OBJECTIVE: To assess sub-clinical cognitive dysfunctions in stable chronic 
obstructive pulmonary disease (COPD) patients having no hypoxemia vs. 
age-matched healthy volunteers using (i) an electrophysiological test: Auditory 
event related potential, P300 test and (ii) a questionnaire tool: Mini-mental 
state examination (MMSE) questionnaire.
MATERIALS AND METHODS: EIGHTY MALE SUBJECTS WERE INCLUDED: 40 stable COPD 
patients (smoking history >20 pack years) and 40 healthy volunteers (HVs). Age, 
duration of illness, smoking pack years, and spirometric indices were assessed. 
MMSE scores were evaluated in these groups. Latency of P300 wave and amplitude 
of P300 wave were studied in both groups to detect P300 abnormalities in COPD 
group. Correlations of P300 abnormalities with patient characteristic parameters 
and MMSE scores were assessed. In addition, individual COPD patients having 
significant cognitive dysfunctions beyond cut-off value of 99(th) percentile of 
HVs were analyzed.
RESULTS: We observed significantly prolonged P300 latency (P < 0.001) and 
decreased P300 amplitude (P < 0.001) in COPD group. MMSE scores were 
significantly reduced in COPD group (P < 0.001). 10/40 COPD patients had 
prolongation of P300 latency, and 27/40 COPD patients had reduced MMSE scores 
beyond 99(th) percentile of HV. However, we did not observe any statistically 
significant correlation between P300 abnormalities and patients' characteristics 
or MMSE scores (P > 0.05 for all).
CONCLUSIONS: Our study explores cognitive dysfunctions in stable COPD patients 
with no hypoxemia. This study highlights the relative importance of using MMSE 
and P300. Cognitive dysfunctions were detected both by MMSE and P300; however, 
MMSE abnormalities were more frequent compared to P300 abnormalities (27/40 vs. 
10/40) in COPD patients.

DOI: 10.4103/0970-2113.106119
PMCID: PMC3644834
PMID: 23661909

Conflict of interest statement: Conflict of Interest: None declared


12. Neuroimage. 2012 Aug 1;62(1):239-49. doi: 10.1016/j.neuroimage.2012.04.041. Epub 
2012 Apr 28.

Separating neural and vascular effects of caffeine using simultaneous EEG-FMRI: 
differential effects of caffeine on cognitive and sensorimotor brain responses.

Diukova A(1), Ware J, Smith JE, Evans CJ, Murphy K, Rogers PJ, Wise RG.

Author information:
(1)Cardiff University Brain Research Imaging Centre, School of Psychology, 
Cardiff University, Cardiff, UK.

The effects of caffeine are mediated through its non-selective antagonistic 
effects on adenosine A(1) and A(2A) adenosine receptors resulting in increased 
neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, 
can modify BOLD FMRI signal responses through both its neural and its vascular 
effects depending on receptor distributions in different brain regions. In this 
study we aim to distinguish neural and vascular influences of a single dose of 
caffeine in measurements of task-related brain activity using simultaneous 
EEG-FMRI. We chose to compare low-level visual and motor (paced finger tapping) 
tasks with a cognitive (auditory oddball) task, with the expectation that 
caffeine would differentially affect brain responses in relation to these tasks. 
To avoid the influence of chronic caffeine intake, we examined the effect of 250 
mg of oral caffeine on 14 non and infrequent caffeine consumers in a 
double-blind placebo-controlled cross-over study. Our results show that the 
task-related BOLD signal change in visual and primary motor cortex was 
significantly reduced by caffeine, while the amplitude and latency of visual 
evoked potentials over occipital cortex remained unaltered. However, during the 
auditory oddball task (target versus non-target stimuli) caffeine significantly 
increased the BOLD signal in frontal cortex. Correspondingly, there was also a 
significant effect of caffeine in reducing the target evoked response potential 
(P300) latency in the oddball task and this was associated with a positive 
potential over frontal cortex. Behavioural data showed that caffeine also 
improved performance in the oddball task with a significantly reduced number of 
missed responses. Our results are consistent with earlier studies demonstrating 
altered flow-metabolism coupling after caffeine administration in the context of 
our observation of a generalised caffeine-induced reduction in cerebral blood 
flow demonstrated by arterial spin labelling (19% reduction over grey matter). 
We were able to identify vascular effects and hence altered neurovascular 
coupling through the alteration of low-level task FMRI responses in the face of 
a preserved visual evoked potential. However, our data also suggest a cognitive 
effect of caffeine through its positive effect on the frontal BOLD signal 
consistent with the shortening of oddball EEG response latency. The combined use 
of EEG-FMRI is a promising methodology for investigating alterations in brain 
function in drug and disease studies where neurovascular coupling may be altered 
on a regional basis.

Copyright © 2012 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.neuroimage.2012.04.041
PMCID: PMC3778750
PMID: 22561357 [Indexed for MEDLINE]


13. Acta Neurobiol Exp (Wars). 2011;71(2):233-43.

Relief of carotid stenosis improves impaired cognition in a rat model of chronic 
cerebral hypoperfusion.

Duan W(1), Chun-Qing Z, Zheng J, Gui L, Huang HQ, Chen KN.

Author information:
(1)Department of Neurology, Southwest Hospital, Third Military Medical 
University, Chongqing, China.

To investigate how cognitive impairment is affected by the relief of bilateral 
carotid stenosis, chronic cerebral hypoperfusion was established through 
stenosis of the bilateral carotid common artery in adult Sprague-Dawley rats. 
Subsequently, the model rats received the intragastric placebo, donepezil (5 mg 
per kg), or surgery to relieve carotid stenosis after bilateral carotid common 
artery stenosis. After carotid stenosis was relieved, the cerebral blood flow 
values significantly increased, and P300 latency and escape latency in the 
Morris water-maze were significantly shortened. The concentrations of 
acetylcholine and norepinephrine in the dorsal hippocampus increased after 
carotid stenosis was relieved. Furthermore, P300 latency and escape latency were 
shortened in the relief-treated group compared to the drug-treated group, and 
acetylcholine levels in the relief-treated group were higher than the 
drug-treated group. No significant difference was found for the norepinephrine 
levels in the dorsal hippocampus between the relief-treated and drug-treated 
groups. Cognitive impairment can be significantly reduced by bilateral carotid 
stenosis relief, and the effect of relieving stenosis on cognitive dysfunction 
is superior to the effect of administering an acetylcholinesterase inhibitor.

PMID: 21731077 [Indexed for MEDLINE]


14. Int J Chron Obstruct Pulmon Dis. 2010 Feb 18;5:21-7.

Event-related evoked potentials in chronic respiratory encephalopathy.

Al Tahan AR(1), Zaidan R, Jones S, Husain A, Mobeireek A, Bahammam A.

Author information:
(1)Department of Medicine, College of Medicine, King Saud University, Riyadh, 
Saudi Arabia.

BACKGROUND: Cognitive event-related potential (P(300)) is an index of cognitive 
processing time. It was found to be prolonged in dementia, renal, and hepatic 
encephalopathies, but was not extensively assessed in respiratory failure.
OBJECTIVE: To evaluate P(300) changes in patients with respiratory failure, and 
especially those with mild or subclinical hypoxic-hypercapnic encephalopathy.
METHODS: Auditory event-related evoked potential P(300) latency was measured 
using an oddball paradigm in patients with respiratory failure due to any cause 
(partial pressure of oxygen in arterial blood (PO(2)) should be 75 mm/Hg or 
less). Apart from blood gases measurement, patients underwent the Mini-Mental 
State Examination (MMSE). Patient performances were compared with that of 
matched normal control. Patients were admitted into the study from outpatient 
clinics and wards at King Khalid University Hospital and Sahara Hospital.
RESULTS: Thirty-four patients (12 women, 22 men) were admitted to the study. 
Ages ranged from 19-67 years with a mean of 46.1 years. Respiratory failure was 
severe or very severe in 11 patients (33%), and mild or moderate in the rest 
(66%). Mean value for PO(2) and partial pressure of carbon dioxide in arterial 
blood (PCO(2)) were 63.7 and 45.2 mm/Hg, respectively. pH mean was 7.4 and O(2) 
saturation was 90.7%. P(300) latency ranged from 218 to 393 milliseconds, with a 
mean of 338.4 milliseconds. In comparison with control (309.9 milliseconds), 
there was a significant difference (P = 0.007). P(300) amplitude differences 
were not significant. No significant difference in MMSE was noted between mild 
and severe respiratory failure. Results of detailed neuropsychological 
assessment were clearly abnormal but were limited by the small number of tested 
patients. P(300) latency changes correlated significantly with age as well as 
severity of respiratory failure. P(300) was also significantly delayed whether 
hypoxia occurred with or without hypercapnia.
CONCLUSION: Results show a significant delay of P(300) latency in patients with 
severe and mild respiratory failure. This was associated with subclinical 
encephalopathy in most patients, evidenced by a near-normal MMSE score. Apart 
from confirming the importance of P(300) latency measurement as a marker of 
respiratory encephalopathy, this study asserts the causal relationship between 
hypoxemia and cognitive derangement. Furthermore, it promotes the early use of 
oxygen therapy in a selected group of patients with mild or moderate respiratory 
failure, who have responsibilities which involve taking rapid critical 
decisions.

PMCID: PMC2846153
PMID: 20368908 [Indexed for MEDLINE]


15. Clin Neurophysiol. 2009 Sep;120(9):1693-8. doi: 10.1016/j.clinph.2009.07.034. 
Epub 2009 Aug 14.

Auditory event-related potential changes in chronic occupational exposure to 
organophosphate pesticides.

Dassanayake T(1), Gawarammana IB, Weerasinghe V, Dissanayake PS, Pragaash S, 
Dawson A, Senanayake N.

Author information:
(1)Department of Physiology, Faculty of Medicine, University of Peradeniya, 
Peradeniya 20400, Sri Lanka. tlag23@yahoo.co.uk

OBJECTIVE: To determine whether chronic occupational exposure to 
organophosphates (OP) pesticides leads to cognitive impairment using 
event-related potentials (ERPs).
METHODS: ERPs of 38 vegetable farmers applying OP pesticides and 35 controls 
were recorded using an auditory oddball paradigm. The N1, P2, N2 and P300 ERP 
components and the number of counting errors were compared between the groups.
RESULTS: The farmers made significantly more counting errors than controls in 
the oddball task. The mixed model ANOVA of component latencies revealed a 
significant componentxgroup interaction, suggesting farmers had a greater delay 
in later ERP components. Intergroup comparisons of individual components showed 
significant delays in N2 and P300 latencies. Subsequent ANCOVA showed 
significant P300 delay even after adjusting for the latency of the preceding 
component, N2. Intergroup differences of P300 amplitudes were not significant, 
although there was limited evidence of a difference in scalp topography.
CONCLUSION: Our findings indicate that chronic low-level occupational exposure 
to OP pesticides is associated with progressively increasing delay in successive 
ERP components, particularly P300.
SIGNIFICANCE: Chronic exposure to OP pesticides may delay the neurophysiological 
processes underlying early stages of selective attention and late stages of 
sensory information processing that include stimulus evaluation and updating of 
working memory.

DOI: 10.1016/j.clinph.2009.07.034
PMCID: PMC3145119
PMID: 19683468 [Indexed for MEDLINE]


16. Neurol India. 2001 Dec;49(4):350-4.

Utility of P300 auditory event related potential in detecting cognitive 
dysfunction in patients with cirrhosis of the liver.

Sexena N(1), Bhatia M, Yoshi YK, Garg PK, Tandon RK.

Author information:
(1)Department of Gastroenterology, All India Institute of Medical Sciences, 
Ansari Nagar, New Delhi - 110029, India.

The P300 event related potential (P3ERP) latency has recently been advocated for 
detection of cognitive disturbances in early encephalopathy associated with 
chronic liver disease. The present study was undertaken to assess the magnitude 
of cognitive dysfunction, a marker of subclinical hepatic encephalopathy (SHE), 
in India, using this widely recommended test. One hundred and one patients with 
cirrhosis of the liver (17 females, 84 males; Age 43.3 +/- 11 years, 33 
alcoholic, 49 viral induced, 19 cryptogenic) attending our tertiary care 
hospital were studied. P300 responses were elicited by the standard 'auditory 
odd ball paradigm'. A value of mean+2SD of the latency obtained in 40 age 
matched controls was established as a cut off to define latency prolongation in 
patients. The mean P3ERP latency of cirrhotics (363.6 +/- 32.1 msec) was 
significantly longer (p<0.05) than those of controls (347.8 +/- 24.8 msec). No 
difference was found in the latencies of cirrhotics with or without alcoholic 
aetiology of liver disease. 21 (20.8%) cirrhotics were found to have SHE i.e. 
latency prolongation beyond the cutoff value. A higher proportion of patients in 
advanced stage of liver disease had prolongation in latencies (p<0.02) compared 
to less severe cases. Till the time a gold standard is derived for detection of 
SHE, P3ERP latencies seem to be a reasonable method for detection as well as 
follow up of patients. Since SHE is considered as a preclinical stage of overt 
encephalopathy, it would be worthwhile screening cirrhotics for cognitive 
disturbances using P3ERP latencies and administering prompt therapeutic action.

PMID: 11799406 [Indexed for MEDLINE]


17. Arq Neuropsiquiatr. 2000 Jun;58(2A):262-71. doi: 
10.1590/s0004-282x2000000200010.

[Evidence of cerebral involvement in the chronic stage of Chagas disease 
obtained using the P300 potential and quantified electroencephalography].

[Article in Spanish]

Prost JO(1), Romero Villanueva H, Morikone AM, Polo G, Bosch AM.

Author information:
(1)Servicio de Neurología, Sección de Neurofisiología, Hospital Bernardino 
Rivadavia, Buenos Aires, Argentina. hrsneu@intramed.net.ar

It is already known the involvement of the peripheral nervous system in chronic 
stages of Chagas disease. Tomographic and neuropsychological evidence of brain 
compromise has been included recently. In order to evaluate the 
neurophysiological counterpart of cerebral involvement, we studied P300 evoked 
potential and quantified EEG (qEEG) of 35 patients (26-55 years), and compared 
to an equal number of control subjects (29-55 years). We have found increased 
P300 latency compared to the control group (331.24 +/- 24. 02 vs 318.86 +/- 
23.18) (p=0.01716). qEEG showed lower relative Beta 1 power in the patients 
group (p=1.6E5), and the principal frequency 1 Hz slower in the same group 
(p=0.01077). Multivariate analysis showed three subpopulations: a normal one, 
pathological one with higher Alpha power and pathological with Alpha decrement 
and DeltaTheta increment. Pathological findings represented 20% for the qEEG and 
11.43% for cognitive potentials. Cardiac and neurologic involvement were not 
correlated. We conclude that there is clear electrophysiological evidence of 
cerebral involvement in chronic Chagas disease, thus reinforcing findings 
obtained by other methods.

DOI: 10.1590/s0004-282x2000000200010
PMID: 10849625 [Indexed for MEDLINE]


18. Arch Gen Psychiatry. 1998 Feb;55(2):173-80. doi: 10.1001/archpsyc.55.2.173.

First-episode schizophrenic psychosis differs from first-episode affective 
psychosis and controls in P300 amplitude over left temporal lobe.

Salisbury DF(1), Shenton ME, Sherwood AR, Fischer IA, Yurgelun-Todd DA, Tohen M, 
McCarley RW.

Author information:
(1)Harvard Medical School, Department of Psychiatry, McLean Hospital, Belmont, 
Mass., USA.

Erratum in
    Arch Gen Psychiatry 1998 May;55(5):413.

BACKGROUND: Schizophrenia is associated with central (sagittal) midline 
reductions of the P300 cognitive event-related potential and topographic 
asymmetry of P300, with reduced left temporal voltage. This P300 asymmetry is, 
in turn, linked to tissue volume asymmetry in the posterior superior temporal 
gyrus. However, it is unknown whether P300 asymmetry is specific to 
schizophrenia and whether central and lateral P300 abnormalities are due to 
chronic morbidity, neuroleptic medication, and/or hospitalization, or whether 
they are present at the onset of illness.
METHODS: P300 was recorded in first-episode schizophrenia, first-episode 
affective psychosis, and control subjects (n = 14 per group). Subjects silently 
counted rare (15%) target tones (1.5 kHz) among trains of standard tones (1.0 
kHz). Averages were constructed from brain responses to target tones.
RESULTS: Peak amplitude of P300 and integrated voltage over 300 to 400 
milliseconds were significantly different between first-episode schizophrenics 
and controls over the posterior sagittal midline of the head. First-episode 
schizophrenics displayed smaller amplitudes over the left temporal lobe than 
first-episode affective psychotics and controls, but the groups showed no 
differences over the right temporal lobe.
CONCLUSIONS: Left-sided P300 abnormality in first-episode schizophrenia relative 
to first-episode affective psychosis and controls suggests that P300 asymmetry 
is specific to schizophrenic psychosis and present at initial hospitalization. 
This P300 asymmetry suggests left temporal lobe dysfunction at the onset of 
schizophrenia.

DOI: 10.1001/archpsyc.55.2.173
PMCID: PMC2730913
PMID: 9477932 [Indexed for MEDLINE]


19. Intern Med. 1997 Apr;36(4):270-5. doi: 10.2169/internalmedicine.36.270.

Evoked potentials in patients with chronic respiratory insufficiency.

Nakano S(1), Imamura S, Tokunaga K, Tsuji S, Hashimoto I.

Author information:
(1)Department of Internal Medicine, Kumamoto Rosai Hospital.

P300, somatosensory evoked potential (SEP) and brainstem auditory evoked 
potential (BAEP) are widely used neurophysiological methods for objectively 
evaluating cognitive, somatosensory and brainstem auditory functions. We studied 
the P300, SEP and BAEP in 17 patients with chronic respiratory insufficiency 
(PaO2:58.2 +/- 7.0 mmHg; mean +/- SD) and 15 age-matched healthy subjects (PaO2: 
84.4 +/- 11.3 mmHg). The latency and amplitude of P300, the N9 latency, N9-N13 
and N13-N20 interpeak latencies (IPL) in SEP, wave I latency and I-V IPL in BAEP 
were compared between the patients and controls. The P300 latency, N9-N13 and 
N13-N20 IPLs in SEP in the patients were significantly prolonged compared to the 
controls. In contrast, the amplitude of P300, N9 latency in SEP, wave I latency 
and I-V IPL in BAEP were not significantly different between the patients and 
controls. These results suggest that chronic respiratory insufficiency 
influences the cognitive and somatosensory functions, and indicate that there is 
a selective vulnerability of evoked potentials to this condition.

DOI: 10.2169/internalmedicine.36.270
PMID: 9187565 [Indexed for MEDLINE]


20. Kidney Int. 1996 Mar;49(3):833-8. doi: 10.1038/ki.1996.115.

Beneficial effect of renal transplantation on cognitive brain function.

Kramer L(1), Madl C, Stockenhuber F, Yeganehfar W, Eisenhuber E, Derfler K, Lenz 
K, Schneider B, Grimm G.

Author information:
(1)Department of Medicine IV, University of Vienna, Austria.

Cognitive brain dysfunction is a common complication of end-stage renal disease. 
To investigate the cerebral effect of renal transplantation, we studied P300 
event-related potentials--an objective marker of cognitive brain 
function--trailmaking test and Mini-mental state in 15 chronic hemodialysis 
patients and 45 matched healthy subjects. Before transplantation, patients 
showed prolonged P300 latency (364 vs. 337 ms, P < 0.01), smaller amplitude 
(15.2 vs. 19.1 microV) and scored lower (P < 0.05) in trailmaking test and 
Mini-mental state as compared to healthy subjects. Following renal 
transplantation (14 months), P300 latency decreased (337 ms, P < 0.01 vs. 
before) and amplitude increased (17.4 microV, P < 0.05 vs. before), indicating 
improved cognitive brain function. The trailmaking test and Mini-mental state 
tended to improve. Following transplantation, P300 findings, trailmaking test 
and Mini-mental state were not different from healthy subjects. Additional 
studies following erythropoietin treatment in 6 of the 15 hemodialysis patients 
revealed decreased (improved) P300 latency (351 vs. 379 ms before, P < 0.05) 
with further decrease following transplantation (341 ms, P = 0.06). Our findings 
indicate that cognitive brain dysfunction in hemodialysis patients may be fully 
reversed by successful renal transplantation.

DOI: 10.1038/ki.1996.115
PMID: 8648927 [Indexed for MEDLINE]


21. Neurol Med Chir (Tokyo). 1993 Mar;33(3):146-51. doi: 10.2176/nmc.33.146.

Influence of regional cerebral blood flow on event-related potential (P300).

Kuwata T(1), Funahashi K, Maeshima S, Ogura M, Hyotani G, Terada T, Itakura T, 
Hayashi S, Komai N.

Author information:
(1)Department of Neurological Surgery, Wakayama Medical College.

The relationships between event-related potential (P300), higher brain 
functions, and regional cerebral blood flow (rCBF) were examined in 31 
neurosurgical patients. The P300 latency, evaluated by an acoustic "odd-ball" 
paradigm, was normal in 14 and prolonged in 17 patients. Fourteen of 17 
prolonged P300 patients had reduced rCBF in the right cerebral hemisphere, 
especially the frontal lobe and/or thalamus. There was a significant inverse 
relationship between P300 latency and laterality index (rt rCBF/lt rCBF) in the 
frontal lobe. Prolonged P300 patients revealed significant abnormalities in 
psychological tests compared to normal P300 patients. There were significant 
inverse relationships between the P300 latency and "orientation" and "memory" 
test scores. Decreased rCBF in the right cerebral hemisphere, especially the 
frontal lobe and/or thalamus, is associated with prolonged P300 latency, 
suggesting that the right cerebral hemisphere is important in human cognitive 
processes.

DOI: 10.2176/nmc.33.146
PMID: 7683120 [Indexed for MEDLINE]