Clinical criteria for the diagnosis of Alzheimer's disease include insidious onset and progressive impairment of memory and other cognitive functions. There are no motor, sensory, or coordination deficits early in the disease. The diagnosis cannot be determined by laboratory tests. These tests are important primarily in identifying other possible causes of dementia that must be excluded before the diagnosis of Alzheimer's disease may be made with confidence. Neuropsychological tests provide confirmatory evidence of the diagnosis of dementia and help to assess the course and response to therapy. The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information become available.

https://n.neurology.org/content/neurology/34/7/939.full.pdf

Clinical diagnosis of Alzheimer's disease : report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

/pdf/free-radicals-in-the-physiological-control-of-cell-function-g3w3iyr0ph.pdf

Free Radicals in the Physiological Control of Cell Function

An MRI time course of 512 echo-planar images (EPI) in resting human brain obtained every 250 ms reveals fluctuations in signal intensity in each pixel that have a physiologic origin. Regions of the sensorimotor cortex that were activated secondary to hand movement were identified using functional MRI methodology (FMRI). Time courses of low frequency (< 0.1 Hz) fluctuations in resting brain were observed to have a high degree of temporal correlation (P < 10(-3)) within these regions and also with time courses in several other regions that can be associated with motor function. It is concluded that correlation of low frequency fluctuations, which may arise from fluctuations in blood oxygenation or flow, is a manifestation of functional connectivity of the brain.

Functional connectivity in the motor cortex of resting human brain using echo-planar MRI.

Information about the basal ganglia has accumulated at a prodigious pace over the past decade, necessitating major revisions in our concepts of the structural and functional organization of these nuclei. From earlier data it had appeared that the basal ganglia served primarily to integrate diverse inputs from the entire cerebral cortex and to "funnel" these influences, via the ventrolateral thalamus, to the motor cortex (Allen & Tsukahara 1974, Evarts & Thach 1969, Kemp & Powell 1971). In particular, the basal

/pdf/parallel-organization-of-functionally-segregated-circuits-159qr6wgp1.pdf

Parallel Organization of Functionally Segregated Circuits Linking Basal Ganglia and Cortex

— A method has been developed for the simultaneous measurement of the rates of glucose consumption in the various structural and functional components of the brain in vivo. The method can be applied to most laboratory animals in the conscious state. It is based on the use of 2-deoxy-D-[14C]glucose ([14C]DG) as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissues. [14C]DG is used because the label in its product, [14C]deoxyglucose-6-phosphate, is essentially trapped in the tissue over the time course of the measurement. A model has been designed based on the assumptions of a steady state for glucose consumption, a first order equilibration of the free [14C]DG pool in the tissue with the plasma level, and relative rates of phosphorylation of [14C]DG and glucose determined by their relative concentrations in the precursor pools and their respective kinetic constants for the hexokinase reaction. An operational equation based on this model has been derived in terms of determinable variables. A pulse of [14C]DG is administered intravenously and the arterial plasma [14C]DG and glucose concentrations monitored for a preset time between 30 and 45min. At the prescribed time, the head is removed and frozen in liquid N2-chilled Freon XII, and the brain sectioned for autoradiography. Local tissue concentrations of [14C]DG are determined by quantitative autoradiography. Local cerebral glucose consumption is calculated by the equation on the basis of these measured values.

The method has been applied to normal albino rats in the conscious state and under thiopental anesthesia. The results demonstrate that the local rates of glucose consumption in the brain fall into two distinct distributions, one for gray matter and the other for white matter. In the conscious rat the values in the gray matter vary widely from structure to structure (54-197 μmol/100 g/min) with the highest values in structures related to auditory function, e.g. medial geniculate body, superior olive, inferior colliculus, and auditory cortex. The values in white matter are more uniform (i.e. 33–40 μmo1/100 g/min) at levels approximately one-fourth to one-half those of gray matter. Heterogeneous rates of glucose consumption are frequently seen within specific structures, often revealing a pattern of cytoarchitecture. Thiopental anesthesia markedly depresses the rates of glucose utilization throughout the brain, particularly in gray matter, and metabolic rate throughout gray matter becomes more uniform at a lower level.

The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat.

HE BLOOD FLOW AND OXYGEN METABOLISM of the human brain has been studied intensively since Kety developed the inert gas method in 1945. More than 200 clinical studies employing this method have been published so far, and now the former terra incognita is well mapped out. The information gained from all these studies will form the subject of the present review. It will also include, however, the results obtained by an indicator injection technique which has been applied to the measurement of cerebral blood flow in man to a much more limited extent. The early results obtained in this particular field have been reviewed by Schmidt (292) and Kety (156-163) and by other authors (38, 61, 76, 2 I 6, 281, 307). The aim of the present review is to offer an up to date presentation of the subject, and, in particular, to discuss certain aspects in greater detail. The general field of cerebral circulation was reviewed by Wolff in 1936 (348), by many authors in a comprehensive study in 1938 (41), and extensive bibliographic compilations of original contributions from 1938 to 1952 have also been published (255, 256). The pharmacology of the cerebral circulation alone, which has recently been reviewed by Sokoloff (318), forms an overwhelming body of knowledge. In the present study great emphasis will be put on information regarding cerebral oxygen consumption in man, whereas only scant attention will be paid to the intermediary metabolism of the brain. Himwich in I 951 published an excellent review (142) of much of the pertinent literature in this rapidly expanding field. Reference is also made to the recent study by Sokoloff (3 I 9). The first attempt to measure the cerebral blood flow in man was made in 1941 by observing the displacement of spinal fluid caused by compression of the

Cerebral blood flow and oxygen consumption in man.

1. Previous studies in man have revealed a coupling between the regional cerebral blood flow (rCBF) and the regional cerebral metabolic rate for oxygen. In normal man, increases in the regional cerebral metabolic rate for oxygen leads to proportional increases in the rCBF(34). We have measured the rCBF as an expression of the level of cortical activity simultaneously from 254 cortical regions in 28 patients with no major neurological defects, during rest and during planning and execution of a few types of learned voluntary movements with the hand. 2. We found that the rCBF increases exclusively in the supplementary motor area while subjects were programming a sequence of fast isolated movements of individual fingers, without actually executing it. 3. During execution of the same motor sequence, there were equivalent increases of the rCBF in both supplementary motor areas, but only in the contralateral primary motor area. In addition, there were more modest rCBF increases in the contralateral sensory hand area, the convexity part of the premotor area, and bilaterally in the inferior frontal region. 4. Repetitive fast flexions of the same finger or a sustained isometric muscular contraction raise the blood flow in the contralateral primary motor and sensory hand area. 5. A pure somatosensory discrimination of the shapes of objects, without any concomitant voluntary movements, also leaves the supplementary motor areas silent. 6. We conclude that the primary motor area and the part of the motor system it projects to by itself can control ongoing simple ballistic movements with the self-same body part. A sequence of different isolated finger movements requires programming in the supplementary motor areas. We suggest that the supplementary motor areas are programming areas for motor subroutines and that these areas form a queue of time-ordered motor commands before voluntary movement are executed by way of the primary motor area.

Supplementary motor area and other cortical areas in organization of voluntary movements in man

Multi-infarct dementia. A cause of mental deterioration in the elderly.

The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localised within the brain

Cerebral blood flow was studied by the arteriovenous oxygen difference method in patients with severe hypertension and in normotensive controls. The blood pressure was lowered to study the lower limit of autoregulation (the pressure below which cerebral blood flow decreases) and the pressure limit of brain hypoxia. Both limits were shifted upwards in the hypertensive patients, probably as a consequence of hypertrophy of the arteriolar walls. These findings have practical implications for antihypertensive therapy.When the blood pressure was raised some patients showed an upper limit of autoregulation beyond which an increase of cerebral blood flow above the resting value was seen without clinical symptoms. No evidence of vasospasm was found in any patient at high blood pressure. These observations may be of importance for the understanding of the pathogenesis of hypertensive encephalopathy.

https://www.bmj.com/content/bmj/1/5852/507.full.pdf

Niels A. Lassen

Papers

Cerebral blood flow and oxygen consumption in man.

Supplementary motor area and other cortical areas in organization of voluntary movements in man

Multi-infarct dementia. A cause of mental deterioration in the elderly.

The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localised within the brain

Autoregulation of brain circulation in severe arterial hypertension.