190 Journal ofNeurology, Neurosurgery, and Psychiatry 1992;55:190-194 Association of atrophy of the medial temporal lobe J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.3.190 on 1 March 1992. Downloaded from with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer's disease K A Jobst, A D Smith, C S Barker, A Wear, E M King, A Smith, P A Anslow, A J Molyneux, B J Shepstone, N Soper, K A Holmes, J R Robinson, R A Hope, C Oppenheimer, K Brockbank, B McDonald Abstract lateral temporal lobes are related to the degree A combination of medial temporal lobe of cognitive decline,"8 but such findings are atrophy, shown by computed tomo- difficult to reconcile with neuropathological graphy, and reduced blood flow in the studies showing that the most severely affected parietotemporal cortex, shown by single parts of the brain in Alzheimer's disease are in photon emission tomography, was found the medial lobe, mainly the amygdala, the in 86% (44151) of patients with a clinical hippocampal formation and adjacent parahip- diagnosis of senile dementia of the Alz- pocampal gyrus.>'3 Atrophy of these areas can heimer type (SDAT). The same combina- be revealed in life by CT studies in which the tion ofchanges was found in four out of 10 scan angle is adjusted to give a clearer view of patients with other clinical types of the medial temporal lobe, and such studies in dementia and in two out of 18 with no patients with a clinical diagnosis ofAlzheimer's evidence of cognitive deficit. Of the 12 disease have, indeed, shown severe damage to patients who died, 10 fulfilled histopatho- structures in the medial temporal lobe.'""6 logical criteria for Alzheimer's disease, However, atrophy of the medial temporal lobe nine ofthem having a clinical diagnosis of is also found in other conditions-notably, SDAT, and one a clinical diagnosis of epilepsy and hypoxia,'7 schizophrenia,'8 and multi-infarct dementia. All 10 patients amnesia'9-and so is not unique to dementia of Radcliffe Infirmary, with histopathologically diagnosed Alz- the Alzheimer's type. Oxford OX2 6HE University heimer's disease had shown a combina- In none of the CT and SPET studies des- Department of tion ofhippocampal atrophy and reduced cribed above were the two procedures carried Clinical Neurology parietotemporal blood flow in life. In 10 out in the same patients. The purpose of our K A Jobst A Wear patients (nine with SDAT) out of 12 in report is to describe CT studies ofthe temporal E M King whom the hippocampal atrophy was lobe and SPET studies of perfusion of the A Smith more noticeable on one side of the brain cortex in the same group of patients. We University than on the other the parietotemporal wished to see whether there was any relation http://jnnp.bmj.com/ Department of perfusion deficit was also asymmetrical, Pharmacology between atrophy of the medial temporal lobe A D Smith being greater on the side showing more and a perfusion deficit in the parietotemporal Department of hippocampal atrophy. These results sug- cortex and, if so, whether such a relation was Neuroradiology gest that the combination of atrophy of associated with Alzheimer's disease defined C S Barker the hippocampal formation and reduced clinically and, when possible, by histopatho- P A Anslow A J Molyneux bloodflowin the parietotemporal regionis logical criteria. Preliminary findings have been a feature of dementia of the Alzheimer on September 24, 2021 by guest. Protected copyright. Department of reported.20 Neuropathology type and that the functional change in the B McDonald parietotemporal region might be related University to the loss ofthe projection neurons in the Patients and methods Department of parahippocampal gyrus that innervate Patients were recruited, after having been Nuclear Medicine, John Radcliffe this region of the neocortex. given a full explanation of the study protocol, Hospital, Oxford from general practitioners and hospital based B J Shepstone services, with some subjects entering them- N Soper CT has shown that many patients with a selves. Ethical approval for the study was K A Holmes clinical of senile dementia of the Littlemore Hospital, diagnosis obtained from both the Central Oxford Oxford Alzheimer type (SDAT) display more Research and the Psychiatric Sector Research J R Robinson appreciable cerebral atrophy than expected for ethics committees. Informed consent was ob- K Brockbank their age.' Functional changes in the brains of tained from those without cognitive deficit, and University demented patients have been found by meth- for those with a significant deficit it was given by Department of Psychiatry, ods that show cerebral blood flow, or uptake of a close relative. Subjects were referred with Warneford Hospital, glucose, oxygen or radioligands: the most varying degrees of mental deterioration and Oxford frequent finding is a functional deficit in the memory loss, many for detailed screening with R A Hope posterior parietal and temporal lobes ofthe cor- a view to making a diagnosis. Diagnoses were C Oppenheimer tex.2" Single photon emission tomography made according to DSM-III-R criteria. Drug Received 11 March 1991 and in revised form 10 June 1991. (SPET) has recently been used to show that the treatment remained unchanged during screen- Accepted 18 July 1991 functional deficits in the posterior parietal and ing. Association ofatrophy of the medial temporal lobe with reduced bloodflow in the posterior parietotemporal cortex 191 Figure CT in the SPET studies were carried out with an J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.3.190 on 1 March 1992. Downloaded from temporal lobe orientation intravenous injection of 500 MBq hexamethyl- of a patient who was not propyleneamine oxime (HMPAO) labelled clinically demented (top) as a and a patient with a with technetium-99m, which was given clinical diagnosis of senile bolus and prepared according to the manufac- dementia of the Alzheimer turer's instructions (Ceretec, hexametazime, type (SDA T) (bottom). Sixty four SPET The arrows indicate the Amersham Intemational). thinnest part of the medial images were obtained over 360°, each having an temporal lobe adjacent to acquisition time of 20 s and a resolution of the brain stem where a x 64 Axial and coronal slices were linear measurement was 64 pixels. taken. The left of the brain reconstructed by filtered back projection and is shown on the right, were two pixels in width (13 mm). SPET scans where there is also a scale were assessed blind to the clinical diagnosis on in cm. The non-demented patient was aged 80 at the a scale of zero to three, in which 0 represented time of the scan, while the no perfusion deficit, 1 a minimal to mild deficit, patient with SDA T was 82; the respective right 2 a moderate deficit, and 3 a severe perfusion medial temporal lobe deficit "breaching" the cortex. To localise and thicknesses were 17 5 mm grade the deficits more accurately scans were and 10 mm. assessed in both transverse and coronal planes. Grading was done alongside the CT scan so as to identify perfusion deficits in which intra- cerebral pathology was clearly discernible (such as a cerebral infarct) and accounted for the observed SPET perfusion anomaly. Any CT evidence of appreciable atrophy of the parietal lobe was also noted. SPET perfusion scores in the left, right, or bilateral parietotem- poral regions with a grading of 2 or more were considered to indicate a clear perfusion deficit for the purpose of subsequent analysis. Each subject was assessed with the CAMDEX.21 The cognitive section, CAM- COG, includes sections for testing memory, praxis, language, attention, concentration, orientation, abstract thinking, and calculation and has a maximum score of 107. It also enables the derivation of the mini mental state examin- ation, which is scored out of 30. A score of less than 80 in the CAMCOG and of less than 24 in the MMSE was considered to indicate a sig- nificant cognitive deficit. Neuropathological examination was perfor- A detailed clinical and psychiatric history med on cerebral hemispheres that had been http://jnnp.bmj.com/ was taken from each subject, followed by a suspended in buffered neutral formalin for at full physical examination of all systems, blood least six weeks. Histological sections were tests to exclude identifiable metabolic causes prepared from the frontal, temporal, and of memory loss and dementia, and neuro- parietal neocortex, hippocampus, cerebellum, psychological screening with the Cambridge midbrain, and pons. Sections were stained with mental disorders of the elderly examination haemotoxylin and eosin, congo red, luxol and (CAMDEX).2' Screening specifically included fast blue cresyl violet and with methenamine on September 24, 2021 by guest. Protected copyright. CT and SPET of the brain. silver22 and Cross's modification of the CT scans were taken in the axial plane with Palmgren stain23 in order to demonstrate argy- 4 mm contiguous sections through the pos- rophylic plaques and neurofibrillary tangles, terior fossa and 8 mm contiguous sections respectively. Alzheimer's disease was diag- through the cerebrum parallel to the orbito- nosed if the diagnostic criteria proposed by meatal line. After this procedure and starting Khachaturian were fulfilled,24 taking into with a lateral topogram sections were then account any clinical history of dementia. taken passing through the front of the hard palate and top of the mastoids in 4 mm parallel sections through the temporal lobes; this scan Results plane is approximately 20 degrees caudad to the Clinical diagnosis orbitomeatal line. Left and right medial tem- Fifty one of the 79 patients fulfilled the DSM- poral lobe width (combined hippocampal for- III-R criteria for SDAT and could be further mation and parahippocampal gyrus) was then categorised, as shown in the table, into those measured from the film, using calipers, at the who were thought to have SDAT alone and narrowest point adjacent to the brain stem those with other central nervous system disease (figure 1).