|Year : 2015 | Volume
| Issue : 3 | Page : 188-193
Neurophysiological and psychometric evaluation of cognition in the normal aging population
Ann A Abdel Kader1, Ebtesam M Fahmy2, Ayatallah F Ahmed1, Omneya R Ameen3, Amira A Labib1, Alshaimaa S Khalil1
1 Department of Special Medicine, Faculty of Medicine Clinical, Neurophysiology Unit, Cairo University, Cairo, Egypt
2 Department of Neurology, Cairo University, Cairo, Egypt
3 Department of Psychiatry, Cairo University, Cairo, Egypt
|Date of Submission||23-Mar-2015|
|Date of Acceptance||23-May-2015|
|Date of Web Publication||13-Aug-2015|
Amira A Labib
Clinical Neurophysiology Unit, Cairo University, 52 Mosadak st., Dokki 12611, Cairo
Source of Support: None, Conflict of Interest: None
Assessment of cognitive function in normal aging has been considered as an important issue nowadays. There is a generalized proportional decline in mental processing speed among elderly adults that affects all elements of mentation equally.
The aim of this study was to assess cognitive functions in normal elderly individuals using psychometric cognitive assessment scales and electrophysiological studies including late cortical responses, P300 and contingent negative variation (CNV).
Thirty-five healthy elderly individuals of both sexes were included. Their ages ranged from 60 to 75 years. The participants were subjected to thorough clinical assessment, cognitive evaluation using psychometric scales and neurophysiological tests in the form of P300 and CNV.
The results of P300 showed a significant positive correlation between reaction time and age. A significant negative correlation was found between reaction time and performance on the Wechsler Intelligence Scale (WIS) (P = 0.03). The mean amplitude of P300 wave recorded from the parietal region was significantly greater in male participants than in female participants. As regards the results of CNV, a significant negative correlation was noted between N2 latency and the verbal scale of WIS.
Comparison of the mean CNV parameters between male and female participants showed that the mean latency of P2 wave was significantly higher in the male population compared with the female population. No significant correlation was revealed between P300 and CNV parameters and scores of Wechsler Memory Scale subtests and parameters of Wisconsin Card Sorting Test.
Results suggest that the psychiatric scales do not provide a substitute for electrophysiological tests in evaluating the cognitive changes that occur with normal aging. However, there was a limitation for the study in detecting changes because of the narrow age range of the cases.
Keywords: aging, contingent negative variation, cognition, P300, psychometric
|How to cite this article:|
Abdel Kader AA, Fahmy EM, Ahmed AF, Ameen OR, Labib AA, Khalil AS. Neurophysiological and psychometric evaluation of cognition in the normal aging population. Egypt J Neurol Psychiatry Neurosurg 2015;52:188-93
|How to cite this URL:|
Abdel Kader AA, Fahmy EM, Ahmed AF, Ameen OR, Labib AA, Khalil AS. Neurophysiological and psychometric evaluation of cognition in the normal aging population. Egypt J Neurol Psychiatry Neurosurg [serial online] 2015 [cited 2018 Feb 24];52:188-93. Available from: http://www.ejnpn.eg.net/text.asp?2015/52/3/188/162041
| Introduction|| |
Aging refers to decline in component biologic processes occurring with senescence, which results in impaired brain structure, cognitive performance, and behavior. Aging affects all body systems, from cell to thought . Cognitive functions tend to decline with aging, and this decline is evident especially when changes in behavior or rapid responses are needed .
The frontal areas of the human brain are differentially affected. Areas of the frontal cortex are assumed to constitute functional networks. For a specific task, each area within such a network is thought to perform a specific function . Studies on effects of age on the contingent negative variation (CNV) have reported the most severe reduction in amplitude early after the warning stimulus over the frontal areas ,. CNV can be recorded in the serial conditions of habituation-reinforcement-motor extinction (free attention)-reinforcement-motor extinction (forced attention). The mean CNV amplitude under reinforcement and motor extinction (free attention) conditions decreases with aging .
P300 event-related potential (ERP) is thought to assess cognitive functions, including attention, allocation, and activation of immediate memory. It is defined as the most positive point of the average waveform to the target tones after 250 ms and before 600 ms .
However, some studies have revealed that P300 is affected by biological processes such as fluctuations in the arousal state of participants. P300 measures not only depend on the cognitive state but also on multiple other factors; of these, participant's age is one of the most important factors .
This study aimed to evaluate cognitive functions in normal elderly individuals, using psychometric cognitive assessment battery and late cortical responses, P300 and CNV.
| Participants and methods|| |
This was a case-control study carried out on 35 healthy elderly individuals. All recruited participants were above 60 years of age, with normal neurological examination, normal CT or MRI brain, normal hearing, mini-mental state score greater than 24, the Hamilton depression scale score greater than 7, and they had variable levels of education. Patients were divided into two groups: the male group, which included 19 men, with a mean of 65 ± 3.3 years and the female group, which included 16 women, with a mean of 65.8 ± 4.5 years.
We excluded from the study illiterate individuals, those with an mini-mental state score 24 or less, Hamilton depression scale score less than 7, and those with profound psychological problems or diminshed hearing. All of them agreed with the terms of the informed consent.
All participants were subjected to thorough clinical assessment, including careful general medical assessment and complete neurological examination according to the standard sheet of the Neurological Department, Cairo University Hospitals.
Routine laboratory investigations were carried out, including fasting and postprandial blood sugar level, lipid profile, liver and kidney function tests, complete blood count, ESR, uric acid, and evaluation of Na, K, and calcium levels. These tests were performed for exclusion of any systemic diseases. Brain imaging (CT or noncontrast MRI) was performed at the department of Diagnostic Radiology to exclude any organic brain lesions.
Cognitive assessment using the following tests:
- Psychometric assessment included the Wechsler Adult Intelligence Scale, which measures general intellectual function, the Wechsler Memory Scale (WMS), which provides measures of various aspects of memory function, and the Wisconsin Card Sorting Test (WCST), which is a well-established measure of executive function.
- Electrophysiological studies for late cortical evoked potentials were carried out: P300 wave was recorded at the Clinical Neurophysiology Unit, Cairo University hospitals, using auditory oddball paradigm.
Three active electrodes were placed at Fz, Cz, and Pz according to the 10-20 international system of electroencephalography electrodes placement. The reference electrode was placed over either mastoid (M) process. The ground electrode was placed on the forehead.
The gain was initially set at 50 μV per (vertical) division. Monitor time was 0.2 s. Band pass was 0.1-50 Hz (value of low cuts and high cuts, respectively). The common tone frequency was 2 kHz with an initial intensity of 75 dB. However, the rare tone frequency was 8 kHz with an initial intensity 75 dB too.
Disc electrodes were placed over the scalp with an adhesive gel after properly cleaning the skin. The active electrode was applied at Cz. The reference electrode and the ground were applied to ear lobule and FPz, respectively. The electrode impedance was kept below 5 kΩ. A total of 200 auditory stimuli (bursts) were presented to the ears through earphones. Tones were chiefly background tones, whereas the rarer ones were target tones. The participant was instructed to press the button as quickly as possible on hearing the infrequent tones. These tones were presented randomly intermixed.
To verify reproducibility of the response, the procedure was repeated at least twice. The responses were displayed on a screen and could be printed out. For each participant, P300 latency, amplitude, and reaction time were obtained to detect any significant abnormality.
Contingent negative variation
Three active electrodes were placed at Fz, Cz, and Pz according to the 10-20 international system of EEG electrode placement. The reference electrode was placed over either mastoid (M) process. The ground electrode was placed on the forehead. Thus, the recording channels were Fz-A, Cz-A, and Pz-A.
The gain was initially set at 50 μV per (vertical) division. Monitor time was 0.5 s. Band pass was 0.01-20 Hz (value of low and high cuts, respectively). The first stimulation is an auditory stimulation with a tone frequency of 3 kHz and an initial intensity of 80 dB. The second stimulation is flash stimulation with a light emission diode goggle of 10 Hz frequency.
Two waves were identified, for which latency and amplitude of each were measured: the first wave from baseline to the first peak, and the second wave from the second peak to the following dip.
Data were analyzed using SPSSwin (statistical package for social science), version 20 (SPSS, IBM, Chicago, USA).
Numerical data were expressed as means and SDs or medians and ranges as appropriate. Qualitative data were expressed as frequencies and percentages.
For quantitative variables, comparison between the two groups was made using Student's t-test. Bivariate correlation analysis was carried out to assess the correlation between age and different variables, whether on neurophysiological tests or on psychometric tests. Pearson's correlation coefficient was used and correlation was significant at 0.05 level or 0.01 level (two-tailed) according to comparisons after Bonferroni adjustment. Independent Student's t- test was used to correlate between sex and different measurements in our study. A P-value less than 0.05 was considered significant. Trend-wise significance was considered for a value less than 0.08 and greater than 0.05.
| Results|| |
General characteristics of the study population
The study was carried out on 35 healthy elderly individuals, 19 were men (54.3%) and 16 were women (45.7%). Their ages ranged between 60 and 75 years, with a mean age of 66 ± 3.8 years. They were all educated; 26 participants (74.3%) had 6 years of compulsory formal primary education, seven participants (20%) were high-school graduates, and two participants (5.7%) were university graduates. They were all right-handed (before education). They underwent normal general and neurological examination.
Results of the psychometric scales
The minimum, maximum, and mean scores of the psychometric battery (WIS, WMS, and WCST) are represented in [Table 1], [Table 2] and [Table 3].
|Table 1: Minimum, maximum, and mean scores of WIS subtests in the study population|
Click here to view
|Table 2: Minimum, maximum, and mean scores of wechsler memory scale subtests in the study population|
Click here to view
|Table 3: Minimum, maximum, and mean scores of wisconsin card sorting test parameters in the study population|
Click here to view
Results of the neurophysiological studies
- P300 wave: the mean latency of P300 at Fz, Cz, and Pz was 423.56, 426.13, and 424.32 ms, respectively. The mean amplitude of P300 at Fz, Cz, and Pz was 4.44, 4.14, and 3.74 μV, respectively. The mean value of the reaction time was 2528.27 ms.
- CNV: the mean latency of N1, P1, N2, and P2 was 297.22, 445.44, 2107.53, and 2291.29 ms, respectively. The mean amplitude of N1 and N2 was 13.51 and 16.14 μV, respectively.
No statistically significant difference was found between the two groups as regards mean age (P = 0.49).
- WIS subtest scores: the mean score of vocabulary subtest and the total score of the performance scale were significantly higher among men compared with women (P = 0.03 and 0.04, respectively). Moreover, there was a trend-wise significant increase in the total score of the verbal scale among men compared with women (P = 0.07). Otherwise, no significant difference was noted (P > 0.05).
- WMS subtests scores: no statistically significant difference was observed between male and female participants as regards WMS mean scores (P > 0.05).
- WCST parameters: no statistically significant difference was observed between male and female participants as regards the mean scores of WCST parameters (P > 0.05).
- Mean P300 parameters: The mean amplitude of P300 wave recorded from the parietal region was significantly greater in men than in women (P = 0.04). Otherwise, no statistically significant differences were found between men and women (P > 0.05) [Figure 1].
|Figure 1: Comparison of mean P300 amplitudes between male and female elderly participants.|
Click here to view
- Mean CNV parameters: comparison of the mean CNV parameters between men and women showed that the mean latency of P2 wave was significantly higher in men than in women (P = 0.02). Otherwise, no significant differences were noted (P > 0.05) [Figure 2].
|Figure 2: Comparison of mean contingent negative variation latencies between male and female elderly participants.|
Click here to view
- Correlations of neurophysiological and psychometric parameters with age:
- WIS subtest scores: no significant correlation was found between age and mean scores of WIS subtests (P > 0.05).
- WMS subtest scores: no significant correlation was found between age and mean scores of WMS subtests (P > 0.05).
- WCST parameters: a trend-wise significant positive correlation was found between mean value of preservative runs and age (P = 0.06).
- P300 parameters: a significant positive correlation was found between age and the reaction time (P = 0.04). No significant correlation was detected between age and other P300 parameters (P > 0.05).
- CNV parameters: a significant negative correlation was observed between age and latency of N2 and P2 waves (P = 0.03 and 0.01, respectively). No significant correlation was detected between age and other CNV parameters (P > 0.05).
- Correlations between neurophysiological parameters and psychometric scales:
- P300: a significant negative correlation was seen between performance on the WIS and reaction time (P = 0.03). Otherwise, no significant correlation was found between P300 parameters and other WIS, WMS, or WCST scores (P > 0.05).
- CNV: a significant negative correlation was noted between the verbal scale of WIS and N2 latency (P = 0.002). Otherwise, no significant correlation was detected between CNV and other WIS, WMS, or WCST parameters.
Sensitivity of the neurophysiological studies in relation to the psychometric tests
Taking the psychometric subtests as a gold standard we found the following:
- Digital total with latency P300: sensitivity = 75%; specificity = 47%.
- Digital span with latency P300: sensitivity = 73%; specificity = 21%.
- Digital span with amplitude P300: sensitivity = 46.2%; specificity = 73.7%.
- Digital total with amplitude P300: sensitivity = 35.7%; specificity = 52.9%.
- Mental control with amplitude P300: sensitivity = 41.2%; specificity = 60%.
- Mental control with latency of N1: sensitivity = 29.4%; specificity = 78.6%.
| Discussion|| |
ERPs provide significant data to understand normal and abnormal brain aging, as they reflect the time-course of perceptual, attention-related, and cognitive process .
In this study, the mean amplitude of P300 wave recorded from the parietal region was significantly higher among men compared with women. This was in disagreement with that reported by Picton et al. , who found a significant difference between male and female healthy elderly individuals as regards P3 amplitude (with women having larger P3s). Schiff et al.  also reported higher P300 amplitude in women compared with men; they stated that the greater P300 amplitude in women cannot be ascribed to differences in skull thickness, because in that case sex should have affected not only the amplitude of P300, but also the other ERP components. However, Elwan et al.  found no statistically significant difference between men and women as regards P3 amplitude. Thus, we can conclude that the sex difference in ERPs implies a difference in the rate of change in neural and cognitive processes with aging.
As regards latency of P300, no statistically significant difference was detected between men and women. This was in agreement with that reported by Picton et al. , who found no differences in latency as regards sex. However, Mullis et al. , who recorded P300 in healthy individuals ranging from 8 to 90 years of age, found that female participants had significantly shorter P3 latencies compared with male participants. On comparing latencies of P300 recorded from the frontal, central, and parietal regions, no statistically significant difference was noted. This finding was in agreement with that reported by Pfefferbaum et al. , who found that P3 becomes more uniformly distributed from Pz to Fz with age. This may be due to changes in overlapping components such as the slow wave rather than to changes in the amplitude of P300 per se. This could also be attributed to the fact that P300 has multiple generators and can be recorded from several cortical and subcortical locations ,.
On correlating P300 parameters with age, a significant positive correlation was noted between age and the reaction time. This finding was in agreement with those of Mattay et al.  and Vallesi et al. , who showed delayed reaction time with age. The reaction time measurement concerns with the speed of individuals' response to either external or internal stimulus. It is not a simple response, but it involves other factors such as perception, sensation, attention, short-term memory, decision making, and motor behavior, and these factors may be affected with aging .
In the present study, there was no significant correlation between age and P300 parameters. However, Goodin et al.  reported a marked increase in the latency of the P3 component with increased age. Several studies have also reported reductions in the amplitude and/or changes in the scalp distribution of P3 with age . Polich  and Schiff et al.  found that P300 latencies increase with age in contrast with their amplitude, which decreases along the lifespan. These studies were conducted on healthy elderly participants. This could be attributed to the fact that the present study was not conducted on a wide age group and thus the difference between age and P300 parameters could not be detected.
On correlating P300 parameters with scores of WIS subtests, a significant negative correlation was seen between performance scale and reaction time. As reaction time represents the timing of mental events, prolonged reaction time correlates negatively with better scores on performance scale. This is to some extent met with findings of Walhovd and Fjell , who found negative correlation between P300 latency and WIS parameters and positive correlation between the amplitude of P300 and WIS parameters.
No significant correlation was found between P300 parameters and scores of WMS subtests or parameters of WCST. However, no sufficient studies were available at this point. It can be attributed to the fact that the cognitive psychometric tests and P300 latencies (indicate memory updating) and amplitudes (represent attention) do not change the same way with aging.
As regards CNV, a significant negative correlation was observed between age and latency of N2 and P2 waves. There was no significant difference between age and the rest of parameters of CNV waves. This is in contrast to the studies of Hillman et al. , who reported increased CNV amplitude in elderly participants, which may reflect increased preparation of the task-relevant processes. A limitation of both studies is the few number of electrodes used, making it impossible to examine topographic differences of the CNV, and the narrow age range. In contrast to an increased CNV amplitude in elderly participants, Michalewski et al.  showed a selective age-related CNV amplitude reduction over the frontal areas, whereas the potential at the vertex and at parietal sites did not change with age. Other studies found a reduced CNV amplitude in older participants , or a lack of amplitude differentiation between hemispheres . These inconsistencies in age-related effects on the CNV may be due to different task difficulties or due to task-related variables such as fatigue.
In our study, a significant negative correlation was noted between latency of N2 and verbal scale. As N2 represents the time needed for motor preparation , this inverse correlation is consistent with better performance on the WIS. In conclusion, the results of this study suggest that the psychiatric scales do not provide a substitute for electrophysiological tests in evaluating the cognitive changes that occur with normal aging.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Raz N, Rodrigue KM. Differential aging of the brain: patterns, cognitive correlates and modifiers. Neurosci Biobehav Rev 2006; 30
Bryan J, Luszcz MA, Crawford JR. Verbal knowledge and speed of information processing as mediators of age differences in verbal fluency performance among older adults. Psychol Aging 1997; 12
Petrides M. Frontal lobes and behaviour. Curr Opin Neurobiol 1994; 4
MacPherson SE, Phillips LH, Della Sala S. Age, executive function, and social decision making: a dorsolateral prefrontal theory of cognitive aging. Psychol Aging 2002; 17
West RL. An application of prefrontal cortex function theory to cognitive aging. Psychol Bull 1996; 120
Verleger R, Wascher E, Arolt V, Daase C, Strohm A, Kömpf D. Slow EEG potentials (contingent negative variation and post-imperative negative variation) in schizophrenia: their association to the present state and to Parkinsonian medication effects. Clin Neurophysiol 1999; 110
Polich J, Kok A. Cognitive and biological determinants of P300: an integrative review. Biol Psychol 1995; 41
Kügler CF, Taghavy A, Platt D. The event-related P300 potential analysis of cognitive human brain aging: a review. Gerontology 1993; 39
Rugg MD, Coles MGH. Electrophysiology of mind. Oxford: Oxford University Press; 1995.
Picton TW, Stuss DT, Champagne SC, Nelson RF. The effect of age on human event-related potentials. Psychophysiology 1984; 21
Schiff S, Valenti P, Andrea P, Lot M, Bisiacchi P, Gatta A, Amodio P. The effect of aging on auditory components of event-related brain potentials. Clin Neurophysiol 2008; 119
Elwan O, Hassan AA, Abdel Naseer M, Fahmy M, Elwan F, Abel Kader A, Mahfouz M. Brain aging in normal Egyptians: neuropsychological, electrophysiological and cranial tomographic assessment. J Neurol Sci 1996; 136
Mullis RJ, Holcomb PJ, Diner BC, Dykman RA. The effects of aging on the P3 component of the visual event-related potential. Electroencephalogr Clin Neurophysiol 1985; 62
Pfefferbaum A, Ford JM, Wenegrat BG, Roth WT, Kopell BS. Clinical application of the P3 component of event-related potentials. I. Normal aging. Electroencephalogr Clin Neurophysiol 1984; 59
Duncan CC. Brain potentials in normal and disordered attention: findings in search of a theory. In: Presidential address presented at the annual meeting of the society for psychophysiological research. Chicago; 2003
Nieuwenhuis S, Aston-Jones G, Cohen JD. Decision making, the P3, and the locus coeruleus-norepinephrine system. Psychol Bull 2005; 131
Pelosi L, Blumhardt LD. Effects of age on working memory: an event-related potential study. Brain Res Cogn Brain Res 1999; 7
Mattay VS, Fera F, Tessitore A, Hariri AR, Berman KF, Das S, et al
. Neurophysiological correlates of age-related changes in working memory capacity. Neurosci Lett 2006; 392
Vallesi A, Stuss DT, McIntosh AR, Picton TW. Age-related differences in processing irrelevant information: evidence from event-related potentials. Neuropsychologia 2009; 47
Goodin DS, Squires KC, Henderson BH, Starr A. Age-related variations in evoked potentials to auditory stimuli in normal human subjects. Electroencephalogr Clin Neurophysiol 1978; 44
:447-458. Cited in: Polich and Kok .
Brown WS, Marsh JT, LaRue A. Exponential electrophysiological aging: P3 latency. Electroencephalogr Clin Neurophysiol 1983; 55
Polich J. Meta-analysis of P300 normative aging studies. Psychophysiology 1996; 33
Walhovd KB, Fjell AM. The relationship between P3 and neuropsychological function in an adult life span sample. Biol Psychol 2003; 62
Hillman CH, Weiss EP, Hagberg JM, Hatfield BD. The relationship of age and cardiovascular fitness to cognitive and motor processes. Psychophysiology 2002; 39
Michalewski HJ, Thompson LW, Smith DB, Patterson JV, Bowman TE, Litzelman D, Brent G. Age differences in the contingent negative variation (CNV): reduced frontal activity in the elderly. J Gerontol 1980; 35
Golob EJ, Ovasapyan V, Starr A. Event-related potentials accompanying motor preparation and stimulus expectancy in the young, young-old and oldest-old. Neurobiol Aging 2005; 26
Rohrbaugh JW, Syndulko K, Lindsley DB. Brain wave components of the contingent negative variation in humans. Science 1976; 191
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]