Age vs. aging in the pathogenesis of senile dementia of the Alzheimer type: electrophysiological evidence.

Is senile dementia of the Alzheimer type (SDAT) the end result of aging of the brain (serial or aging-related model) or the result of some other mechanism that runs in parallel to normal aging (parallel or age-related model)? This question can be answered by comparing variables that measure biological aging (aging-dependent variables, ADVs) of normal individuals and of SDAT patients. If the serial model applies, the values of the ADVs of SDAT patients should be at the upper end of the normal ADV curves. In control individuals the power of the alpha band in the 2-Hz flash-stimulated EEG at the posterior head regions increased with age, while the power of the delta band in the resting EEG at the anterior head regions decreased. In SDAT patients the ADVs were significantly different from normal and opposite to the trend of normal aging, supporting the parallel model and suggesting that the pathogenesis of SDAT is different from normal aging.

Cognition-related EEG abnormalities in nondemented Down syndrome subjects.

Down syndrome (DS) subjects develop Alzheimer disease (AD) histopathology before they develop dementia. We compared the resting and flash stimulated electroencephalogram (EEG) of nondemented adult DS and age-matched control subjects, in search of EEG abnormalities that might correlate with AD histopathology. DS subjects had increased absolute power in all the EEG bands, independent of cognition functions measured by the Mini Mental State Examination and Picture Absurdities Test scores. In the power spectrum of the resting EEG, we found a cognition-related increase in power at 4.5 and 8.8 Hz, indicative of alpha-slowing, as in AD patients. In the stimulated EEG, we found several cognition-related abnormalities, such as decreased responses to 12-Hz stimulation and decreased integral of beta- and gamma-band responses, indicative of decreased responsiveness to photic stimulation, as in AD patients. Therefore, nondemented DS and AD patients share several cognition related EEG abnormalities which are probably due to AD histopathology.

Severity of dementia correlates with loss of broad-band visual cortical responses.

We have shown that the response to flash stimulation of the occipital electroencephalogram (EEG) in Alzheimer disease (AD) patients is smaller than in normal subjects. To ascertain whether this is a specific feature of AD or a nonspecific effect of dementia, we investigated in AD and multi-infarct dementia (MID) patients the relationship between cognitive function, measured as Mini-Mental State Examination score, and EEG power response, measured as the difference in spectral power between flash-stimulated EEG and resting EEG. Both variables were positively correlated and the regression equations of AD and MID patients were not significantly different, showing nonspecificity. The coupling between cognitive function and power response is discussed in relation to the dynamic binding hypothesis of cognition.

Decreased alpha bandwidth responsiveness to photic driving in Alzheimer disease.

The power spectra of the photically activated occipital EEGs of 9 mildly to moderately demented probable Alzheimer disease (AD) patients (according to NINCDS-ADRDA criteria), 9 normal age-matched control and 27 normal subjects of different ages were compared. In normal subjects, photic stimulation with rhythmic flashes ranging between 2 and 20 Hz elicited a characteristic response in each EEG bandwidth (delta, theta, alpha, beta1 and beta2). The magnitude of each bandwidth response was a function of the frequency of the photic stimulus. In AD patients the alpha bandwidth response curve was significantly smaller than that of age-matched controls (MANOVA main effect of group, P = 0.018); all the other bandwidth response curves were normal. Therefore, in AD there is a selective abnormality in the alpha bandwidth responsiveness to photic stimulation, probably due to AD pathology in the neuronal generator of the alpha rhythm.

The visualization of myosatellite cells in normal and denervated muscle: a new light microscopic staining technique.

A new light microscopic staining technique allows the visualization of satellite cells on the surface of myofibers. Either prior to or during fixation, whole frog sartorius muscles are bathed in an acidic buffered solution containing lead nitrate and subsequently exposed to ammonium sulfide. The staining of the satellite cells resulting from this procedure reveals their positions, and the outlines of their cell processes which occasionally branch. Electron microscopy shows that the staining is due to lead deposits localized between apposing membranes of satellite cells and associated myofibers. Prior exposure to N-ethyl-maleimide (NEM) does not alter the formation of the lead deposits on the satellite cell, but reduces the amount of Pb deposits on the muscle surface and connective tissue. This technique has been applied to determine the effects of denervation on the satellite cells of frog sartorius muscles. Four weeks after denervation, the number of satellite cells is essentially the same in both denervated muscles and the intact muscles of the contralateral side. However, denervation results in a subpopulation of satellite cells with altered shapes. They have elongated cytoplasmic processes which often branch. It is suggested that these supernumerary cytoplasmic processes represent an intermediate phase in the transition of satellite cells to myoblasts.

Neurotrophic control of RNA synthesis in amphibian striated muscle.

When frog sartorius muscles are incubated in culture for 3 days, a 98% increase in RNA synthesis by the muscles is seen. A portion of this increase (60--100% in different experiments) is prevented by the presence of a 2 cm distal nerve stump left attached to the muscle, or by the addition to the culture medium of nerve and spinal cord extracts from frog, rat or cow. The effect of the nerve stump and the extract is seen under conditions of neuro-muscular blockade by 50 mg/l gentamicin sulfate present in the culture medium. Autoradiography of 1 micrometer sections of muscles previously labeled with [3H]uridine shows that isotope incorporation is largely confined to muscle fibers rather than connective tissue. Muscles cultured for 3 days display normal action and resting potentials either in the presence or absence of extract. The results are discussed in terms of control of muscle RNA synthesis by substances present in motor neurons.

Uncoupling cell junctions in a glandular epithelium by depolarizing current.

The high electrical conductance linking adjacent border cells in Chironomus salivary gland is depressed reversibly when current is passed outward from one of the cells, though not when current is passed inward. This "uncoupling" is closely associated with an electrically induced increase in conductance in the (nonjunctional) membrane of that cell.

Permeability of a cell membrane junction. Dependence on energy metabolism.

The ion permeability of the membrane junctions between Chironomus salivary gland cells is strongly depressed by treatments that are generally known to inhibit energy metabolism. These treatments include prolonged cooling at 6 degrees -8 degrees C, and exposure to dinitrophenol, cyanide, oligomycin, and N-ethylmaleimide. Intracellular injection of ATP appears to prevent depression of junctional permeability by dinitrophenol or to reverse it. Ouabain, azide, p-chloromercuriphenylsulfonic acid, reserpine, and acetazolamide fail to depress junctional permeability. Thus the ion permeability of the junctional membranes appears to depend on energy provided by oxidative phosphorylation. Possible energy-linked processes for maintaining junctional permeability are discussed, including processes involving transport of permeability-modifying species such as Ca(++).