Changes in Brain Functional Connectivity in Alzheimer-Type and Multi-Infarct Dementia

Abstract

Clinical and neuropathological evaluation of elderly subjects with dementia has traditionally concentrated upon the focal distribution of brain disease, ignoring changes in the complex connections that link brain areas and that are crucial for cognition. We examined subjects with the two most common forms of dementia in the elderly (dementia of the Alzheimer type or DAT, and multi-infarct dementia or MID); and used electroencephalographic (EEG) coherence to examine the effects of these illnesses on the functional connections between brain areas. We studied coherence between brain areas known to be linked by two different types of connections: (i) dense narrow bands of long corticocortical fibres; (ii) broad complex networks of corticocortical and corticosubcortical fibres. Areas that were linked by dense narrow bands of long corticocortical fibres showed greatly diminished coherence in subjects with DAT; among MID subjects, this coherence was not significantly affected. Areas that were linked by broad connective networks showed the largest decreases in coherence among MID subjects. These findings are consistent with neuropathological evidence that Alzheimer's disease is a neocortical 'disconnection syndrome' in which there is a loss of structural and functional integrity of long corticocortical tracts. The findings further suggest that the vascular disease of MID most prominently affects broad fibre networks that may be more vulnerable to diffuse subcortical vascular damage. A ratio of coherence from complex corticocortical-corticosubcortical networks divided by coherence from long corticocortical tracts correctly classified 76% of subjects into DAT and MID categories. Overall, these results indicate that EEG coherence detects basic pathophysiological differences between subjects with DAT and MID, and that these differences may be clinically useful.

Decreased EEG synchronization in Alzheimer’s disease and mild cognitive impairment

“…This finding is consistent with earlier EEG studies using coherence between pairs of electrodes [20,24,25] . However, the assumptions underlying the present results and the results obtained with coherence differ considerably: The coherence studies contain an implicit local source model by assuming that the signal recorded at one electrode represents only the activity underneath that electrode and not activity from other sources.…”

“…It is thus not clear whether the GFS In general, the method seems to be promising for further EEG research, since its computation relies on few assumptions that allow a comprehensive interpretation and since its global characteristics simplify statistics. Furthermore, it would be of interest to investigate whether previously reported differences in EEG coherence between AD and other typed of dementia (i.e vascular dementia [24] ) are similarly reflected in GFS.…”

Individual analysis of EEG frequency and band power in mild Alzheimer's disease

“…Accordingly, these cholinergic inputs would sustain the power of the alpha rhythm (Holschneider et al, 1998;Villa et al, 2000). This explanation agrees with the reduction of functional cortico-cortical coupling, revealed by EEG coherence studies, in AD patients compared to normal controls (Leocani et al, 2000) and VaD patients (Leuchter et al, 1992). The regulation of the alpha frequency would otherwise be relatively independent of the full integrity of the cholinergic systems and corticocortical connections (mainly impaired in mild AD).…”

Neurophysiologic Correlates of Side Effects in Normal Subjects Randomized to Venlafaxine or Placebo

“…EEG recordings were performed using the QND system (Neurodata, Inc., Pasadena, CA) while subjects rested in the eyes-closed, maximally alert state in a sound-attenuated room with subdued lighting, using procedures previously described in detail (Cook et al, 1998bLeuchter et al, 1992). Electrodes were placed with an electrode cap (ElectroCap; Eaton, OH) using an extended International 10-20 System with 35 recording electrodes ( Figure 1; Cook et al, 1998b).…”

“…Another technologist, blinded to subject identity and treatment condition, reviewed the data for eye movement, muscle, or other artifacts and made a final selection the first 20-32 s of artifact-free data for processing. This amount of data has been used to obtain reliable frequency spectra (Leuchter et al, 1992Brenner et al, 1995). Data were reformatted by amplitude subtraction to construct a linkedears reference.…”