Assessment of CSF homovanillic acid levels distinguishes dementia with Lewy bodies from Alzheimer's disease.

Abstract

Sirs: Dementia with Lewy bodies (DLB) is clinically characterized by fluctuating cognitive impairment, visual hallucinations and parkinsonism [4]. It is the second most common neurodegenerative disease that causes dementia after Alzheimer’s disease (AD). One of the most distinct pathologic features in the brains of DLB patients is the prominent loss of nigrostriatal dopaminergic neurons similar to that in the brains of Parkinson’s disease (PD) patients. The previous SPECT and PET studies have shown that the assessment of nigrostriatal dopaminergic functions is useful in distinguishing between DLB and AD patients [2, 6]. In the present study, we measured the CSF levels of homovanillic acid (HVA), a major dopamine metabolite, in DLB and AD patients. We report here that the assessment of CSF HVA levels is also a possible marker for distinguishing DLB patients from AD patients. Although Weiner et al. [7] previously reported that CSF HVA levels in DLB patients were lower than those in AD patients, the number of samples was small (DLB, n = 8) and they did not show the normal control levels of CSF HVA. Sixty-five patients with PD without dementia (32 men and 33 women, 74.5 ± 5.6 years, mean ± SD), 14 patients with DLB (8 men and 6 women, 74.0 ± 7.8 years), 53 patients with AD (23 men and 30 women, 77.1 ± 6.8 years) and 34 normal control subjects (16 men and 18 women, 76.9 ± 6.4 years) were examined. There were no significant differences in age and gender among the four groups. The clinical diagnosis of DLB was based on the criteria of the consortium on DLB international workshop [4]. All the patients with DLB had at least two of the three core features of DLB (fluctuating cognition, recurrent visual hallucinations, and spontaneous parkinsonism). CT or MRI of the heads of these patients showed no focal brain lesions, including those of cerebrovascular disease. Thus, they were diagnosed as having probable DLB. The clinical diagnosis of AD was based on the NINCDS-ADRDA criteria [5]. The mean Mini-Mental State Examination (MMSE) scores (mean ± SD) were 15.1 ± 5.4 (5 to 23) in the DLB group and 16.1 ± 5.1 (0 to 23) in the AD group. The difference in MMSE scores between the two groups was not significant. The mean Hoehn and Yahr scores were 2.08 ± 0.56 in the PD group and 2.13 ± 0.64 in the DLB group. All the AD patients had no apparent extrapyramidal signs and could walk unassisted. After informed consent was obtained, CSF samples were collected from the patients by lumbar puncture. None of the patients took any antiparkinsonian drugs, neuroleptics, or antidepressants when the lumbar puncture was performed. Three milliliters of CSF was used for routine examination, and an additional 2 ml was stored at –70 °C until analysis. The CSF HVA levels were measured by injection of 80 μl of CSF into a high-performance liquid chromatography (HPLC) system equipped with 16 electrochemical sensors (CEAS Model 5500, ESA, Bedford, MA, USA). The mean CSF HVA values were compared by ANOVA with post hoc Scheffe’s analyses. The study protocol was reviewed and approved by the ethics committee of Tokyo Metropolitan Geriatric Hospital. CSF HVA levels were 37.1 ± 14.4 ng/ml in the control group, 14.5 ± 7.3 ng/ml in the PD group, 10.9 ± 9.0 ng/ml in the DLB group and 22.0 ± 10.9 ng/ml in the AD group (Fig. 1). CSF HVA levels were lower in the PD, DLB and AD groups than in the control subjects (p< 0.001, ANOVA). CSF HVA levels in the DLB and PD groups were much lower than those in the AD group (p< 0.01, ANOVA). The difference in CSF HVA levels between the PD and DLB groups was not significant. The cutoff value of 12.6 ng/ml could distinguish the DLB patients from the AD patients with a sensitivity of 78.6 % and a specificity of 79.2 %. We demonstrated a prominent reduction in CSF HVA levels in DLB patients. This finding is compatible with the pathological features that nigrostriatal dopaminergic neurons are severely degenerated in the DLB brain. As previously reported, CSF HVA levels were also lower in AD patients than in the control subjects [1]. However, CSF HVA levels in DLB patients were much lower than those in AD patients. The analysis of CSF HVA levels may be useful in distinguishing DLB patients from AD patients. Recently, we have shown that CSF Aβ42 levels are decreased and CSF tau levels are normal in DLB patients [3]. Although our results should be confirmed by postmortem examination, decreased As42, normal tau and decreased HVA levels may be the characteristic CSF features of DLB. LETTER TO THE EDITORS