Abstract
BackgroundThe pathological processes underlying dementia are poorly understood and so are the markers which identify them. Carnosinase is a dipeptidase found almost exclusively in brain and serum. Carnosinase and its substrate carnosine have been linked to neuropathophysiological processes.MethodsCarnosinase activity was measured by a flourometric method in 37 patients attending a Geriatric Outpatient Clinic. There were 17 patients without dementia, 13 had Alzheimer's disease (AD) and 7 had mixed dementia (MD).ResultsThe range of serum carnosinase activity for patients without dementia was 14.5 – 78.5 μmol/ml/h. There was no difference in carnosinase activity between patients without dementia (40.3 ± 15.2 μmol/ml/h) and patients with AD (44.4 ± 12.4 μmol/ml/h) or MD (26.6 ± 15 μmol/ml/h). However, levels in the MD group were significantly lower than the AD group (p = 0.01). This difference remained significant after adjusting for gender, MMSE score, exercise, but not age, one at a time and all combined. The effect of other medical conditions did not remove the significance between the AD and MD groups. The MD group, but not the AD group, demonstrated a significant trend with carnosinase activity decreasing with duration of disease (from first recorded date of diagnosis to date of blood collection) (r = -0.76, p = 0.049). There was no association with carnosinase activity and MMSE score in the AD or MD group. Both AD and MD patients on any dementia medication (donepezil, galantamine, memantine) had higher carnosinase activity compared to those not taking a dementia medication. Carnosinase activity was higher in patients who regularly exercised (n = 20) compared to those who did not exercise regularly (n = 17)(p = 0.006).ConclusionThis exploratory study has shown altered activities of the enzyme carnosinase in patients with dementia.
Highlights
The pathological processes underlying dementia are poorly understood and so are the markers which identify them
The Pearson correlation was calculated for relationships among serum carnosinase activity, duration of dementia and mini-mental state examination (MMSE) score
Carnosinase activity for patients without dementia was 14.5 – 78.5 μmol/ml/h, comparable to the adult range determined by Lenney et al (18 – 72 μmol/ml/h) using the same method [31]
Summary
The study population consisted of 17 patients without dementia and 20 patients with dementia. Further analysis showed there was no difference in carnosinase activity between patients without dementia (40.3 ± 15.2 μmol/ml/h) and patients with AD (44.4 ± 12.4 μmol/ml/h) or MD (26.6 ± 15 μmol/ml/ h) (Figure 1). Number of patients Mean age (range) Female gender Mean aterial pressure (mmHg) Duration of dementia (month) Mini-mental state examination (MMSE) score Neuroimaging (CT or MRI) Diet, meat eaten within the last day Exercise, 3 or more times per week Medical Conditions: Arthritis Cardiovascular disease Depression Diabetes Hypothyroidism, treated Parkinson's disease Renal insufficiency Stroke, history TIA, history Dementia medication: Donepezil Memantine Galantamine. Exercise on the day of blood collection showed no difference between patients with dementia and those without dementia, but exercising three or more times a week was associated with an increase in carnosinase activity (n = 37, p = 0.006) (Figure 4)
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