Acta Med Scand 208: 387-388. 1980

PRELIMINARY REPORT

Hypoglycemia in Alzheimer’s Disease

Rolf Adolfsson, Costa Bucht, Folke Lithner and Bengt Winblad

From the UmeH Dementia Research Group, Departments of Psychiatry, Medicine and Pathology, Universiry of Umeci, UmeB, Sweden

ABSTRACT. Glucose tolerance tests (GTT) were performed on patients with a ) dementia of Alzheimer type, b) distal gangrene, c) cerebrovascular disease, and d) on non-diabetic controls. Fasting blood sugar was significantly lower and the areas under the GTT curves were significantly smaller in the dementia group than in the other three groups. It is discussed whether Alzheimer’s disease is a generalized disease not only confined to brain tissue and whether the reduced blood glucose levels could impair the brain transmitter levels.

Key words: Alzheimer’s disease, glucose metabolism Acta Med Scand 208: 387. 1980.

The etiology of the most common dementia, de- mentia of Alzheimer type, is still unknown. The pathology of the brain in this disease is well de- scribed and reports on abnormalities in both catecholaminergic and cholinergic systems have been published. However, it is not known whether or not these defects have any effect on the metabolic systems in the body. Carbohydrate metabolism is dependent, at least in part, on the pituitary hormones, and the catecholaminergic and cholinergic transmitter systems exert an influence on these hormones. Furthermore it has been shown that an impairment of glucose oxidation by reduc- tion of the glucose concentration produces a de- creased synthesis of acetylcholine ( I ) . Accordingly, permanently subnormal blood glucose levels in pa- tients with dementia of Alzheimer type could be due to defects in the transmitter systems. It could also be a possible explanation of the finding of reduced acetylcholine synthesis in this disease. After in vit- ro studies of brain biopsy material it was consid- ered unlikely that a generalized defect in glucose metabolism would cause the diminished acetyl- choline production (4).

PATIENTS AND METHODS Four groups of patients were investigated. Group 1: 24 patients (mean age 70 y.) who fulfilled the criteria of dementia of Alzheimer type (insidious onset, loss of memory, intellectual and personality deterioration, typical non-fluctuating progressive downhill course, absence of hypertension, stroke or other diseases causing dementia); group 2: 247 patients (mean age 71 y.) with distal gangrene; group 3: 62 patients (mean age 68 y.) with cerebrovascular disease; group 4: 32 unselected non- diabetic control patients (mean age 68 y.), most of whom where hospitalized because of deep venous thrombosis or heart failure.

Oral glucose tolerance tests were performed according to a standardized procedure and the areas under the glu- cose tolerance test curves were calculated as described earlier (2).

RESULTS AND DISCUSSION

After excluding all cases with open diabetes, we found significantly lower fasting blood sugar, de- termined by the glucose oxidation method, in group 1 (4.34 mmol/l) than in all other groups: controls (p<0.02), group 2 (p<O.OOS) and group 3 ( p < O . O O S ) . The numerical values of the areas under the glucose tolerance test curves (2) were also significantly smaller in the dementia group than in the other three groups (Fig. I).

The investigation suggests that patients with de- mentia of Alzheimer type have a changed car- bohydrate metabolism with decreased blood glu- cose levels. In order to check whether these results are due to an underlying malabsorption or not, we have undertaken a preliminary study on 9 patients with dementia of Alzheimer type and found normal values in their xylose absorption tests. Seven out of 9 patients had normal results in the vitamin A ab-

Reprint requests to: Dr B. Winblad, Department of Pathology, University of Umeh, S-90187 UmeB, Sweden.

Acta Med Scand 208

388 R . Adolfsson et c r l .

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Fig. I . Oral glucose tolerance test. CVD = cerebrovascu- lar disease, SDAT = dementia of Alzheimer type.

sorption test, the two exceptions having a slightly diminished vitamin A absorption. From these re- sults it would appearthat malabsorption is unlikely.

It seems more likely that the changed carbohy- drate metabolism is due to malfunction in the hor- monal regulation, for example in the brain-pitui- tary-adrenal axis, in which the cholinergic and

dopaminergic transmitter systems play an impor- tant role. Dementia of Alzheimer type has been suggested t o be a generalized disease, not only con- fined to the brain tissue ( 5 ) . Catecholamine deficit somewhere else in the body, e.g. in the liver, might make it difficult to mobilize the carbohydrate stores. An interesting question is to what extent, if at all, dementia of Alzheimer type and diabetes mellitus in old age coexist. It has been suggested (3) that, for the peripheral nervous system, a very slight decrease in glucose levels leads to a rapid exhaustion of the neuronal firing. It remains to be found out whether or not the decreased blood glu- cose levels can impair the acetylcholine synthesis as extensively as found by independent research groups in the brain of patients with dementia of Alzheimer type.

AC KNOWLEDGE M EN TS This study was supported by grants from the Swedish Medical Research Council (12X-5664). Osterman's and Pfannenstill's funds.

REFERENCES I . Gibson, G. E. & Blass, J. P.: Impaired synthesis of

acetylcholine in brain accompanying hypoglycemia and mild hypoxia. J Neurochem 27: 37, 1976.

2. Lithner, F.: Cutaneous erythema, with or without ne- crosis, localized to the legs and feet-a lesion in elder- ly diabetics. Acta Med Scand 196: 333, 1974.

3. Perri, V . , Sacchi, 0. & Casella, L.: Nervous transmis- sion in the superior cervical ganglion of the thiamine- deficient rat. Q J Exp Physiol 55: 25, 1970.

4 . Sims, N. R., Smith, C. C. T., Davison, A. N., Bowen, D. M., Flack, R. H. A. & Snowden, J. S.: Glucose metabolism and acetylcholine synthesis in relation to neuronal activity in Alzheimer's disease. Lancet 1: 333, 1980.

5 . Winblad, B., Adolfsson, R., Gottfries, C.-G., Oreland, L. & Roos, 9. E.: Brain monoamines, monoamine metabolites and enzymes in physiological ageing and senile dementia. Recent Dev Mass Spectrom Biochem Med 1:253, 1978.

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