Renin-angiotensin system blockers affect cognitive decline and serum adipocytokines in Alzheimer's disease.

BACKGROUND: Accumulating evidence indicates an association of Alzheimer's disease (AD) with the metabolic syndrome (MetS), characterized by visceral fat accumulation with insulin resistance and altered secretion of adipocytokines such as adiponectin and leptin. The renin-angiotensin system (RAS) regulates blood pressure and insulin resistance. Recent studies suggest that the RAS plays crucial roles in cognitive functions and that adipocytokines exert neuroprotective activity in the brain. We investigated whether RAS blockers (RASB) affect adipocytokines and cognitive function in patients with AD. METHODS: We studied 78 patients with a diagnosis of probable AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition and 106 nondemented control subjects who visited our clinic with a main complaint of headache or dizziness. We examined retrospectively the effects of RASB on adipocytokines and cognitive decline in patients with AD who were divided into three groups: hypertension treated with RASB (HT-RASB; n = 17), hypertension treated with other antihypertensive drugs (HT-other; n = 34), and no hypertension (non-HT; n = 27). RESULTS: The HT-RASB group had a significantly higher serum leptin level and a relatively larger visceral fat area than the other groups, because of the bias toward patients with MetS in this group. The HT-RASB group also had a significantly lower immunoreactive insulin level, a relatively low homeostasis model assessment as an index of insulin resistance, and a relatively high serum adiponectin level among the three groups. Cognitive decline, estimated on the basis of the mean annual decline using the Hasegawa Dementia Scale score was significantly low in the HT-RASB group. CONCLUSION: Treatment with RASB might modulate serum adipocytokines and glucose homeostasis, potentially slowing cognitive decline in patients with AD.

Gender differences in D-aspartic acid content in skull bone.

In forensic medicine, the personal identification of cadavers is one of the most important tasks. One method of estimating age at death relies on the high correlation between racemization rates in teeth and actual age, and this method has been applied successfully in forensic odontology for several years. In this study, we attempt to facilitate the analysis of racemized amino acids and examine the determination of age at death on the basis of the extent of aspartic acid (Asp) racemization in skull bones. The specimens were obtained from 61 human skull bones (19 females and 42 males) that underwent judicial autopsy from October 2010 to May 2012. The amount of D-Asp and L-Asp, total protein, osteocalcin, and collagen I in the skull bones was measured. Logistic regression analysis was performed for age, sex, and each measured protein. The amount of D-Asp in the female skull bones was significantly different from that in the male skull bones (p = 0.021), whereas the amount of L-Asp was similar. Thus, our study indicates that the amount of D-Asp in skull bones is different between the sexes.

Serial neuroimaging in tolosa-hunt syndrome with acute bilateral complete ophthalmoplegia.

Tolosa-Hunt syndrome (THS) is a very rare, relapsing, and remitting painful ophthalmoplegia caused by nonspecific granulomatous inflammation in the cavernous sinus. To our knowledge, bilateral complete, simultaneous palsies of all 3 cranial nerves associated with extraocular movement have not been reported. We describe the first such patient with bilateral THS that responded quickly to corticosteroid therapy. A 54-year-old man presented with a periorbital and frontal headache with acute bilateral severe blepharoptosis and fixed eyes, which dramatically responded to corticosteroid therapy. He had diabetes mellitus type II. Brain MRI showed granulomatous inflammation in both cavernous sinuses and thickening of the surrounding dura mater of the cranial base, suggesting the coexistence of focal hypertrophic cranial pachymeningitis. Our experience indicates that steroid therapy with strict control of blood sugar should be considered in patients with THS complicated by diabetes. MRI is a valuable tool for serially monitoring the response of lesions to treatment in THS.

Characteristic neuroimaging in patients with tumefactive demyelinating lesions exceeding 30 mm.

BACKGROUND AND PURPOSE: Features of tumefactive demyelinating lesion (TDL) on magnetic resonance imaging (MRI) can facilitate the differential diagnosis of TDL and neoplastic lesions, but vary considerably among patients. The larger TDL grows, the more difficult it becomes to differentiate TDL from neoplastic lesions. The purpose of this study was to elucidate typical MRI features in 12 patients with large TDL (>30 mm in diameter). METHODS: We identified 12 patients with large TDL (six men, six women; age range 17-64 years, median age 27 years) and studied the clinical histories and the results of laboratory and various radiological studies in these patients. All cases of clinically definite multiple sclerosis were diagnosed in accordance with McDonald's revised criteria. RESULTS: Common MRI features of large TDLs included variable degrees of mass effect (71%) and edema (100%), a T2 hypointense rim (79%), venular enhancement (57%), and peripheral restriction on diffusion-weighted images (50%). Ring enhancement (38%), open-ring enhancement (31%), or decreased N-acetylaspartate ratios on magnetic resonance spectroscopy (22%) were less frequently observed. Brain angiography demonstrated venous dilatations on and around the TDL. CONCLUSIONS: The diagnosis of large TDL is challenging. Our findings suggest that multiple venous dilatations on and around TDLs on angiography can facilitate diagnosis.

Cerebrospinal fluid-orexin levels and sleep attacks in four patients with Parkinson's disease.

OBJECTIVES: Sleep attacks (SAs) in Parkinson's disease (PD) are rare, but clinically important because they significantly impair the daily lives of patients. Causes of SAs include long-term activation of dopaminergic (especially D3) receptors. Recent studies suggest that SAs in PD may be related to impairment of hypothalamic orexin neurons, similar to narcolepsy. Whether orexin is associated with long-term activation of dopaminergic receptors remains uncertain. PATIENTS AND METHODS: We measured levels of orexin in samples of spinal cerebrospinal fluid (CSF) from 25 patients with PD, including 9 with excessive daytime sleepiness and 4 with SAs. Furthermore, in the four patients with SAs, the selective dopamine D1/D2 agonist pergolide was substituted for the causative drugs with D3 stimulatory activity, and CSF-orexin levels were measured before and after switching treatment. RESULTS: In the 25 patients with PD, including the 4 patients with SAs, lower CSF-orexin levels were associated with a longer disease duration, which has been linked to a higher incidence of SAs. Switching treatment to pergolide significantly increased CSF-orexin levels and completely resolved SAs in the four patients with PD. CONCLUSION: Despite the small number of patients studied, our results suggest that orexin transmission is most likely involved in SAs in PD and that abrogation of D3 receptor stimulation may increase orexin and thereby inhibit SAs.