What EEG findings are characteristic of Alzheimer disease?

Updated: Oct 09, 2019
  • Author: Eli S Neiman, DO, FACN; Chief Editor: Selim R Benbadis, MD  more...
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Answer

Electroencephalography (EEG) is the only clinical diagnostic instrument that directly reflects cortical neuronal functioning. Although the EEG may be normal or minimally disturbed in a number of patients in the initial stages of Alzheimer disease (AD), an abnormal EEG usually is recorded later in the course. A large percentage of patients with moderately severe to severe AD exhibit abnormal EEGs.

In 1981, Stigsby reported diffuse increases of delta and theta frequencies in AD, as well as decreases in the alpha and beta frequency ranges. Frontal slowing was also seen and was more prominent anterior to the sylvian fissure, whereas decreased blood flow was more prominent posterior to the sylvian fissure. These findings may be explained by the observation that EEG reflects the functional decline of the anterior structures, whereas the flow decrease correlates more with the structural damage to the parietal lobe. Frontal slowing probably reflects the loss of functioning of the frontal cholinergic system. [6]

Wada et al showed that EEG coherence provides a measure of functional correlation between 2 EEG signals. [7] They examined intrahemispheric EEG coherence at rest and during photic stimulation in 10 patients with dementia of the Alzheimer type. In the resting EEG, patients with AD had significantly lower coherence than gender and age-matched healthy control subjects in the alpha-1, alpha-2, and beta-1 frequency bands.

EEG analysis during photic stimulation demonstrated that the patients had significantly lower coherence irrespective of the stimulus frequency. [7] The changes in coherence from the resting state to the stimulus condition showed significant group differences in the region of the brain primarily involved in visual functioning. The patients had significantly lower coherence of their EEG reactivity to photic stimulation at 5 and 15 Hz over the posterior head regions.

Thus, patients with AD may have an impairment of interhemispheric functional connectivity in both nonstimulus and stimulus conditions, which suggests a failure of normal stimulation-related brain activation in AD.

Jelic et al found a positive correlation between levels of tau protein in the cerebrospinal fluid (CSF) and the EEG alpha/delta ratio. In a subgroup with high CSF tau levels, a strong relationship between EEG alpha/theta and alpha/delta power was found. No such correlation was found in healthy controls and mildly cognitively impaired individuals with elevated CSF tau levels. [8]

Locatelli et al used EEG coherence to evaluate the functionality of cortical connections and to obtain information about synchronization of regional cortical activity in patients with suspected AD. [9] Alpha coherence was decreased significantly in 6 patients. Significant delta coherence increase was found in a few patients between frontal and posterior regions. The group with AD demonstrated a significant decrease of alpha-band coherence in the temporal-parietal-occipital areas; this was expressed to a greater extent in patients with more severe cognitive impairment.

The investigators theorized that these abnormalities could reflect 2 different pathophysiologic changes, as follows [9] :

  • The alpha coherence decrease could be related to alterations in corticocortical connections

  • The delta coherence increase suggests lack of influence of subcortical cholinergic structures on cortical electrical activity

Strik et al found that the microstates of the resting EEG of patients presenting with mild or moderately severe dementia of the Alzheimer type demonstrated a significant anteriorization of the microstate fields, and the duration of sustained microstates was reduced. [10] These differences were more important than the diffuse slowing. The measurements of microstates may be useful in the early diagnosis of AD. [10]

Muller et al conducted a study comparing single-photon emission computed tomography (SPECT) and quantitative EEG (QEEG) and concluded that whereas QEEG might be as useful as SPECT brain scanning in staging the disease, the correlation with clinical status was weak. [11]

Akrofi et al, employing an automated coherence-based pattern recognition system involving multiple discriminant analysis (MDA) and k-means clustering coherence features from EEG obtained from 56 subjects, were able to distinguish patients with AD from patients with mild cognitive impairment (MCI) and from age-matched controls. This suggests that patients with AD may have a greater number of damaged cortical neurons than patients with MCI and that MCI may be an intermediate step in the development of AD. [12]

Siennicki-Lantz et al studied the relation of cerebral white-matter lesions to AD and found that cerebral blood flow (CBF) in white matter correlated with systolic blood pressure and multichannel EEG in senile dementia of the Alzheimer type. [13]

The presence and functional significance of white-matter lesions in the aging brain or in dementia and the relation of these lesions to blood pressure are unsettled issues. White-matter lesions occur in both cerebrovascular disease and AD. Probably, the white-matter lesions in hypertensive patients are not related to AD but are simply coexisting with it. Their influence on the overall expression of the degree of dementia is unclear; however, it seems intuitively plausible that the lesions should be causing additional cognitive dysfunction.

Siennicki-Lantz et al observed significantly lower white-matter CBF (WMCBF) in patients with AD than in controls. [13] This was more obvious in the posterior cerebral region (ie, the parietal-temporal-occipital area). QEEG from the posterior cerebral regions correlated with WMCBF. Systolic blood pressure was significantly lower in the AD group and was correlated positively with WMCBF in the posterior and anterior brain regions.

Epileptiform activity may occur more frequently in patients with AD than in the general population; clinical tonic-clonic seizures can occur. Bilateral synchronous periodic epileptiform discharges (BiPEDs) (see the first image below), such as triphasic waves (TWs) (see the second image below), may be recorded in AD, usually in the late stages (see Triphasic Waveforms).

Bilateral periodic epileptiform discharges (BiPEDs Bilateral periodic epileptiform discharges (BiPEDs).
Triphasic waves, maximum amplitude bilateral front Triphasic waves, maximum amplitude bilateral frontal.

These findings are not specific for AD because they most often are observed in metabolic disorders, particularly hepatic encephalopathy and other degenerative diseases, such as Creutzfeldt-Jakob disease (CJD). Although there is a good correlation between severity of EEG abnormalities and cognitive impairment, epileptiform discharges or TWs are not predictors of seizures. EEG often can be useful for excluding a superimposed reversible metabolic etiology of dementia and for confirming CJD when the dementia is rapidly progressive.

To investigate the relation between QEEG band powers and CBF, Rodriguez et al studied 42 patients with suspected AD and 18 healthy elderly controls and attempted to differentiate patients with AD from the controls by measuring QEEG and CBF. [14] Regional CBF and QEEG were correlated, especially in the right hemisphere. Significant correlations were found between Mini Mental State Examination (MMSE) scores and relative power of the 2- to 6-Hz and 6.5- to 12-Hz bands on either side and between MMSE scores and left regional CBF; the correlation between MMSE scores and right regional CBF was less strong.

Used together, QEEG and regional CBF had a sensitivity of 88% and a specificity of 89%, with a total accuracy of 88.3%. [14] . QEEG alone showed an accuracy of 77% in the whole group and 69% in those with mild AD; regional CBF alone had an accuracy of 75% in the whole group and 71% in those with mild AD. This study suggests that QEEG and regional CBF measurements, when used together, are reasonably accurate in differentiating AD from healthy aging.

Scheriter et al used clinical examinations, QEEG, neuropsychological testing and neuroimaging to see if distinctions could be made between patients with AD, mixed dementia (vascular), and controls; they found that as would be expected, patients with mixed dementias had more subcortical lesions with increased slow frequency power, which suggested subcortical pathology. [15]

The QEEG high-frequency power was normal in mixed dementia and decreased in AD, probably reflecting the cortical pathology seen in AD. [15] Hachinski scores and neuropsychological testing showed little difference between mixed dementia and AD. QEEG and neuroimaging may be of great use in diagnosing and differentiating these dementia types.

A study that presented a frequency band analysis of AD EEG signals suggested that optimized frequency bands may improve existing EEG-based diagnostic tools for AD, though additional testing on larger AD datasets will be required to verify the effectiveness of the proposed approach. [16]

Oscillatory brain dynamics in AD appear to differ according to age at onset. Young AD patients present with more severe slowing of spontaneous oscillatory activity than old AD patients, which is most pronounced in the posterior brain areas. This finding supports the hypothesis that early-onset AD presents with a distinct endophenotype. [17]

The apolipoprotein E (ApoE) sigma-4 allele is a risk factor for late-onset AD and may have an impact on cholinergic function in AD. Because the cholinergic system has an important role in modulating EEG, impairment of this system may have some relation to the EEG slowing that is characteristic of AD progression.

Lehtovirta et al studied the relation of ApoE to EEG changes. [18, 19] The QEEG of 31 patients with AD was recorded at the early stage of the disease and after a 3-year follow-up. Patients with AD were divided into several subgroups according to the ApoE sigma-4 allele (ie, 2 sigma-4, 1 sigma-4, and 0 sigma-4). These subgroups did not differ in clinical severity or duration of dementia.

The AD patients carrying the sigma-4 allele had more pronounced slow-wave activity than AD patients without the sigma-4 allele, although the disease progression rate did not change. [18, 19] These differences in EEG may suggest differences in the degree of the cholinergic deficit in these subgroups.

The typical electrophysiologic correlates of myoclonus in AD are similar to those of cortical reflex myoclonus, with a focal, contralateral negativity in the EEG preceding the myoclonic jerk. The electrophysiologic correlate of polymyoclonus that can be seen in AD and other pathologic states is a bifrontal negativity in the EEG that precedes the myoclonic jerk. This new type of electrophysiologic correlate of myoclonus may reflect activity of a subcortical generator.


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