ArticlesQuantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer’s disease
Introduction
Much recent research in Alzheimer’s disease (AD) has focused on defining methods for the earliest detection of dementia, preferably in the preclinical stages. The preclinical level of cognitive performance has been useful in predicting the development of dementia [17], [31]. Flicker et al. [12] introduced a new operational term, mild cognitive impairment (MCI), for the condition where there is an evidence of subtle neuropsychological deficits in older subjects before functional impairment becomes apparent and dementia is diagnosed. These authors reported subsequently that there was an 80% probability of further decline in subjects with mild cognitive deficits [13]. Twenty of the patients in the study of Flicker et al. [13] had a Global Deterioration Score (GDS) score of 3, and, after a 2-year follow-up period, 16 were moderately demented (GDS 4). A follow-up study of a larger cohort of memory-impaired nondemented patients showed that 24% developed AD [34]. Petersen et al. [26] followed over 80 MCI patients for almost 54 months and reported that nearly 55% of cases progressed to manifest dementia. Variation of the incidence rates of AD in different studies might be due to the different entry and follow-up criteria applied, as well as to differences in the length of the follow-up period. Because an unknown proportion of MCI patients will develop dementia and thus require therapy, there is a need to support the early intervention using some additional laboratory measures, such as functional neuroimaging methods.
The inclusion of electroencephalography (EEG) examinations in the diagnostic work-up for Alzheimer’s disease is encouraged by its availability and noninvasiveness. Several studies have shown EEG slowing in AD [7], [9], [11], [25]. It has been reported that an abnormal EEG at the early stage of AD may predict a more severe decline in cognitive functions [16]. However, so far, there have been few longitudinal studies of EEG power spectral changes in Alzheimer’s disease. It has been reported that after 2.5 years follow up, both delta and theta activity significantly increased, whereas alpha and beta activity decreased [8]. Other studies have found that progressive EEG slowing could be detected in only a proportion of early AD cases, with 50% showing no deterioration at 12 months follow up [28], [32]. Some authors followed a cohort of healthy subjects and found that low beta power predicted development of cognitive decline after 5 years [11]. Hartikainen et al. [15] found that initially healthy individuals, who after 2 years follow up showed deterioration in learning ability, also had increased delta power. In contrast to these reports, we, in our study, selected at the baseline subjects with objectively verified MCI. In a previous work using discriminant analysis, we defined the best combination of quantitative EEG (qEEG) variables that gave the optimal classification of MCI and AD subjects [18]. We postulated that misclassified MCI subjects might be at risk of developing AD [18].
The comparison of MCI subjects who progress to manifest AD with subjects who remain clinically stable may help us to understand the EEG dynamics of AD. Therefore, in the present study, we evaluated the clinical course of patients with MCI and the incidence of dementia in this group, as well as the pattern of EEG changes following cognitive deterioration and the potential of neurophysiological measures in predicting dementia.
Section snippets
Study sample
The main study sample consisted of 27 subjects with MCI, who at initial examination did not fulfill NINCDS-ADRDA criteria for probable AD [20] and did not have evidence of deterioration in social or occupational functioning. These subjects performed at least 1 SD below average for their age on neuropsychological tests representing one or more areas of cognition, as was described previously [18]. General levels of cognition were assessed by Mini-Mental Test Examination (MMSE) and Full-Scale
Clinical follow up
After a mean follow-up period of 21 months (range 12 to 39 months), 14 patients (52%) were diagnosed as AD and were classified as P MCI. The other 13 patients remained clinically stable and were classified as S MCI.
The P MCI and S MCI groups had slightly different baseline MMSE values (P < 0.05), but they did not differ in Full-Scale Intelligence Quotient scores. There was no difference in the length of follow up between these groups (Table 1). MMSE scores after the follow-up period were
Discussion
The present study shows that 52% of subjects who initially had MCI developed clinically manifest AD after an average follow-up period of 21 months. These results are close to those reported by Petersen et al. [26], except that the follow-up period of their subjects was longer, 54 months on average. Taken together with the data from other studies, which suggest that objective evidence of cognitive impairment can be a reliable predictor of future cognitive decline in the elderly, this study
Acknowledgments
This work was supported by the Swedish Medical Research Council, the Gamla Tjänarinnor Foundation, the Greta Lindenau-Hansells Foundation, the Loo and Hans Ostermans Foundation for Medical Research, the Sandoz Foundation for Gerontological Research, and the Swedish Municipal Pension Institute. All EEG recordings were performed at the Department of Clinical Neurophysiology, Huddinge University Hospital. We thank Anders Persson, head of the Department, and all the staff for the good collaboration.
References (37)
- et al.
EEG coherence in Alzheimer’s disease
Electroencephalogr Clin Neurophysiol
(1994) - et al.
Frequency analysis of the resting awake EEG in mild senile dementia of Alzheimer type
Electroencephalogr Clin Neurophysiol
(1983) - et al.
A longitudinal EEG study of mild senile dementia of Alzheimer typechanges at one year and 2.5 years
Electroenephalogr Clin Neurophysiol
(1985) - et al.
Reduced EEG coherence in dementiastate or trait marker?
Biol Psychiatry
(1994) - et al.
“Mini-Mental State.” A practical method for grading the cognitive state of patients for the clinician
J Psychiatr Res
(1975) - et al.
Brain oscillations and human memoryEEG correlates in the upper alpha and theta band
Neurosci Lett
(1997) - et al.
Regional differences in brain electrical activity in dementiause of spectral power and spectral ratio measures
Electroencephalogr Clin Neurophysiol
(1993) - et al.
Quantitative EEG correlates of cognitive deterioration in the elderly
Neurobiol Aging
(1994) - et al.
Quantitative EEG analysis in early onset Alzheimer’s diseasea controlled study
Electroencephalogr Clin Neurophysiol
(1993) - et al.
Quantitative EEG analysis in early onset Alzheimer’s diseasecorrelations with severity, clinical characteristics, visual EEG and CCT
Electroencephalogr Clin Neurophysiol
(1994)