Pathogenesis Of Vascular Dementia Research Articles

Prevention of Hippocampal Neuronal Damage and Cognitive Function Deficits in Vascular Dementia by Dextromethorphan.

Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37days. Neuron death, glial activation, and cognitive function were assessed at 37days after 2VO (0.2mg/kg, i.p., "DM-0.2" and 2mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD.

Diabetes mellitus and cognitive impairments.

There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer's disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings.

Acupuncture reversed hippocampal mitochondrial dysfunction in vascular dementia rats

Hippocampal mitochondrial dysfunction due to oxidative stress has been considered to play a major role in the pathogenesis of vascular dementia (VD). Previous studies suggested that acupuncture could improve cerebral hypoperfusion-induced cognitive impairments. However, whether hippocampal mitochondria are associated with this cognitive improvement remains unclear. In this study, an animal model of VD was established via bilateral common carotid arteries occlusion (BCCAO) to investigate the alterations of cognitive ability and hippocampal mitochondrial function. BCCAO rats showed impairments in hippocampal mitochondrial function, overproduction of reactive oxygen species (ROS) and learning and memory deficits. After two-week acupuncture treatment, BCCAO-induced spatial learning and memory impairments as shown in Morris water maze were ameliorated. Hippocampal mitochondrial respiratory complex enzymes (complex I, II, IV) activities and cytochrome c oxidase IV expression significantly increased, which might contribute to the reduction of hippocampal ROS generation. In addition, acupuncture significantly improve mitochondrial bioenergy parameters such as mitochondrial respiratory control rate and membrane potential not PDH A1 expression. Placebo-acupuncture did not produce similar therapeutic effects. These findings suggested that acupuncture reversed BCCAO-induced hippocampal mitochondrial dysfunction, which might contribute to its prevention on cognitive deficits.

Tau Protein, Ischemic Injury and Vascular Dementia

Clinical, neuroimaging and neuropathological studies have confirmed overlap between Alzheimer's disease (AD) and vascular dementia (VaD). Classical neuropathological changes of AD (plaques and tangles) can be present in VaD. We review neuroimaging, biochemical and animal studies to consider the role of tau protein in ischemic injury and VaD pathogenesis. The evidence comes largely from transgenic animal studies that confirm that tau transgenes influence cerebral vasculature. Clinicobiochemical studies in the cerebrospinal fluid (CSF) have, similarly, confirmed alterations in both total and phosphorylated tau protein in VaD. These data suggest that tau protein not only serves as a potential diagnostic tool for differential diagnosis of VaD from other types of dementia, but may also be a therapeutic target in ischemic stroke.

Protective activity of carnosine and anserine against zinc-induced neurotoxicity: a possible treatment for vascular dementia.

Carnosine (β-alanyl-L-histidine) is a small dipeptide with numerous beneficial effects, including the maintenance of the acid-base balance, antioxidant properties, chelating agent, anti-crosslinking, and anti-glycation activities. High levels of carnosine and its analogue anserine (1-methyl carnosine) are found in skeletal muscle and the brain. Zinc (Zn)-induced neurotoxicity plays a crucial role in the pathogenesis of vascular dementia (VD), and carnosine inhibits Zn-induced neuronal death. Here, the protective activity of carnosine against Zn-induced neurotoxicity and its molecular mechanisms such as cellular Zn influx and Zn-induced gene expression were investigated using immortalised hypothalamic neurons (GT1-7 cells). Carnosine and anserine protected against Zn-induced neurotoxicity not by preventing increases in intracellular Zn(2+) but by participating in the regulation of the endoplasmic reticulum (ER) stress pathway and the activity-regulated cytoskeletal protein (Arc). Accordingly, carnosine and anserine protected against neurotoxicity induced by ER-stress inducers thapsigargin and tunicamycin. Hence, carnosine and anserine are expected to have future therapeutic potential for VD and other neurodegenerative diseases.

Effects of alpha-lipoic acid on spatial learning and memory, oxidative stress, and central cholinergic system in a rat model of vascular dementia

Brain oxidative stress due to chronic cerebral hypoperfusion was considered to be the major risk factor in the pathogenesis of vascular dementia. In this study, we investigated the protective efficacy of alpha-lipoic acid, an antioxidant, against vascular dementia in rats, as well as the potential mechanism. Bilateral common carotid arteries occlusion (BCCAO) induced severe cognitive deficits tested by Morris water maze (MWM), along with oxidative stress and disturbance of central cholinergic system. However, administration of alpha-lipoic acid (50mg/kg, i.p.) for 28 days significantly restored cognitive deficits induced by BCCAO. Biochemical determination revealed that alpha-lipoic acid markedly decreased the production of malondialdehyde (MDA) and the generation of reactive oxidative species (ROS), and increased the level of reduced glutathione (GSH) in the hippocampal tissue. Additionally, alpha-lipoic acid raised the level of acetylcholine (ACh) and choline acetyltransferase (ChAT) and decreased the activity of acetycholinesterase (AChE) in the hippocampus. These results indicated that treatment with alpha-lipoic acid significantly improved behavioral alterations, protected against oxidative stress, and restored central cholinergic system in the rat model of vascular dementia induced by BCCAO.

Effects of donepezil, an acetylcholinesterase inhibitor, on neurogenesis in a rat model of vascular dementia

Vascular dementia (VaD) is the second most common form of dementia caused by cerebrovascular disease. Several recent reports demonstrated that cholinergic deficits are implicated in the pathogenesis of VaD and that cholinergic therapies have shown improvement of cognitive function in patients with VaD. However, the precise mechanisms by which donepezil achieves its effects on VaD are not fully understood. Donepezil hydrochloride is an acetylcholinesterase inhibitor (AChEI) currently used for the symptomatic treatment of Alzheimer's disease (AD). Several lines of evidence have demonstrated that AChEIs such as donepezil promote neurogenesis in the central nervous system. We investigated whether donepezil regulated hippocampal neurogenesis after bilateral common carotid artery occlusion (BCCAO) in rats, a commonly used animal model of VaD.To evaluate the effect of donepezil on neurogenesis, we orally treated rats with donepezil (10mg/kg) once a day for 3weeks, and injected BrdU over the same 3-week period to label newborn cells. The doses of donepezil that we used have been reported to activate cholinergic activity in rats. After 3weeks, a water maze task was performed on these rats to test spatial learning, and a subsequent histopathological evaluation was conducted. Donepezil improved memory impairment and increased the number of BrdU-positive cells in the dentate gyrus (DG) of BCCAO animals. These results indicated that donepezil improves cognitive function and enhances the survival of newborn neurons in the DG in our animal model of VaD, possibly by enhancing the expression of choline acetyltransferase and brain-derived neurotropic factor.

Statins for the treatment of dementia

The use of statin therapy in established Alzheimer's disease (AD) or vascular dementia (VaD) is a relatively unexplored area. In AD, β-amyloid protein (Aβ) is deposited in the form of extracellular plaques and previous studies have determined Aβ generation is cholesterol dependent. Hypercholesterolaemia has also been implicated in the pathogenesis of VaD. Due to the role of statins in cholesterol reduction, it is biologically plausible they may be efficacious in the treatment of AD and VaD. To assess the clinical efficacy and safety of statins in the treatment of AD and VaD. To evaluate if the efficacy of statins in the treatment of AD and VaD depends on cholesterol level, ApoE genotype or cognitive level. We searched ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (20 January 2014). Double-blind, randomised controlled trials of statins given for at least six months in people with a diagnosis of dementia. Two independent authors extracted and assessed data against the inclusion criteria. We pooled data where appropriate and entered them into a meta-analysis. We used standard methodological procedures expected by The Cochrane Collaboration. We identified four studies (1154 participants, age range 50 to 90 years). All participants had a diagnosis of probable or possible AD according to standard criteria and most participants were established on a cholinesterase inhibitor. The primary outcome in all studies was change in Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) from baseline. When we pooled data, there was no significant benefit from statin (mean difference -0.26, 95% confidence interval (CI) -1.05 to 0.52, P value = 0.51). All studies provided change in Mini Mental State Examination (MMSE) from baseline. There was no significant benefit from statins in MMSE when we pooled the data (mean difference -0.32, 95% CI -0.71 to 0.06, P value = 0.10). Three studies reported treatment-related adverse effects. When we pooled data, there was no significant difference between statins and placebo (odds ratio 1.09, 95% CI 0.58 to 2.06, P value = 0.78). There was no significant difference in behaviour, global function or activities of daily living in the statin and placebo groups. We assessed risk of bias as low for all studies. We found no studies assessing role of statins in treatment of VaD. Analyses from the studies available, including two large randomised controlled trials, indicate that statins have no benefit on the primary outcome measures of ADAS-Cog or MMSE.

NADPH Oxidase 1, a Novel Molecular Source of ROS in Hippocampal Neuronal Death in Vascular Dementia

Chronic cerebral hypoperfusion (CCH) is a common pathological factor that contributes to neurodegenerative diseases such as vascular dementia (VaD). Although oxidative stress has been strongly implicated in the pathogenesis of VaD, the molecular mechanism underlying the selective vulnerability of hippocampal neurons to oxidative damage remains unknown. We assessed whether the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) complex, a specialized superoxide generation system, plays a role in VaD by permanent ligation of bilateral common carotid arteries in rats. Male Wistar rats (10 weeks of age) were subjected to bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]). Nox1 expression gradually increased in hippocampal neurons, starting at 1 week after 2VO and for approximately 15 weeks after 2VO. The levels of superoxide, DNA oxidation, and neuronal death in the CA1 subfield of the hippocampus, as well as consequential cognitive impairment, were increased in 2VO rats. Both inhibition of Nox by apocynin, a putative Nox inhibitor, and adeno-associated virus-mediated Nox1 knockdown significantly reduced 2VO-induced reactive oxygen species generation, oxidative DNA damage, hippocampal neuronal degeneration, and cognitive impairment. We provided evidence that neuronal Nox1 is activated in the hippocampus under CCH, causing oxidative stress and consequential hippocampal neuronal death and cognitive impairment. This evidence implies that Nox1-mediated oxidative stress plays an important role in neuronal cell death and cognitive dysfunction in VaD. Nox1 may serve as a potential therapeutic target for VaD.

Carnosine: A Possible Drug for Vascular Dementia

Carnosine (β–alanyl histidine) is a small dipeptide with numerous beneficial effects, including the maintenance of the acid–base balance, antioxidant, chelating, anti–crosslinking, and anti–glycation activities in the living organism. High levels of carnosine are found in the skeletal muscles and in the brain. We have found that carnosine inhibits Zn2+–induced neuronal death, which plays acrucial role in the pathogenesis of vascular dementia. Our previous research demonstrated that carnosine participates in the Endoplasmic Reticulum (ER)–stress pathway in Zn– induced neurotoxicity and we have applied for a patent related to drugs for Vascular Dementia (VD). Here, we review the roles of carnosine in VD and otherneuro degenerative diseases and discuss perspectives about the future therapeutic use ofthis dipeptide.

Disruption of zinc homeostasis and the pathogenesis of senile dementia

Zinc (Zn) is an essential trace element that is abundantly present in the brain. Although Zn plays crucial roles in learning and memory, numerous studies have indicated that the disruption of Zn homeostasis, namely both depletion and excess Zn, causes severe damage to neurons and is linked with various neurodegenerative diseases including Alzheimer's disease and vascular dementia. Here, we review the current understanding of the role of Zn in the pathogenesis of these neurodegenerative diseases. Based on our findings and other numerous studies, Zn acts as a contributor to Alzheimer's disease in the oligomerization, and as a protector in the neurotoxicity of Alzheimer's β-amyloid protein. Furthermore, Zn plays a central role in ischemia-induced neuronal death and the pathogenesis of vascular dementia. Involvement of Ca(2+) dyshomeostasis and endoplasmic reticulum (ER) stress in the mechanism of Zn-induced neurotoxicity are suggested. We also discuss the possible role of carnosine (β-alanyl histidine), a dipeptide that is present in the brain, as a protective substance for neuronal injury.

Mitochondrial bioenergetic deficits in the hippocampi of rats with chronic ischemia-induced vascular dementia

Vascular dementia (VD), defined as a loss of memory and cognitive function resulting from vascular lesions in the brain, is the second-most-common cause of dementia in the elderly, after Alzheimer’s disease. In recent years, research has focused on the pathogenesis of VD, and mitochondrial bioenergetic deficits have been suggested to contribute to VD onset. To further investigate the role of mitochondria in VD, we used a rat model of VD, which involved permanent bilateral occlusion of the common carotid arteries (with a 1-week interval between artery occlusion to avoid an abrupt reduction in cerebral blood flow) leading to chronic cerebral hypoperfusion. Prior to occlusion, male Wistar rats underwent 7days of Morris water maze training. Only animals that could swim and passed the Morris water maze test were chosen for the study. After 5days of Morris water maze training, mitochondria from the hippocampi of rats, which were randomly selected from animals that could complete the Morris water maze test, were isolated for functional assessment.Mitochondria isolated from the hippocampi of rats from the ischemia group had decreased pyruvate dehydrogenase protein levels, and increased oxidative stress, as manifested by increased hydrogen peroxide production. The ischemia group mitochondria also exhibited decreased respiration coupled to decreased expression and activity of the electron transport chain complex IV (cytochrome c oxidase). These results indicate that the mitochondrial oxidative metabolism is inhibited in the hippocampi of rats following chronic ischemia-induced VD. As the mitochondrial oxidative metabolism deficits, namely mitochondrial bioenergetic deficits directly affect the functions of neurons, it may contribute to VD onset.

Effect of electroacupuncture on the expression of mTOR and eIF4E in hippocampus of rats with vascular dementia

Clinically, electroacupuncture is proved to be an effective therapy for vascular dementia; however, their mechanisms remain uncertain. The aim of the current study was to investigate the mechanism of electroacupuncture therapy for vascular dementia. One month after a vascular dementia animal model was established by bilateral occlusion of common carotid arteries, electroacupuncture treatment was given at "Baihui" (DU20), "Dazhui" (DU14), and "Shenshu" (BL23). Morris water maze was used to assess the learning and memory ability of rats. Western blot assay was performed to detect the expression of mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) in hippocampus of rats. Morris water maze test showed that electroacupuncture improved the learning ability of vascular dementia rats. Western blot assay revealed that the expression level of mTOR and eIF4E in the electroacupuncture group and sham-operated group was higher than that in the vascular dementia group (P < 0.05). In conclusion, the decreasing expression of mTOR and eIF4E plays important roles in the pathogenesis of vascular dementia. Electroacupuncture improves learning and memory ability by up-regulating expression of mTOR and eIF4E in the hippocampus of vascular dementia rats.

Antihypertensive treatment and risk of dementia: a retrospective database study

Vascular risk factors play an important role in the pathogenesis of vascular dementia, as well as in Alzheimer disease. The effect of antihypertensive medication on risk of dementia is unclear. The aim was to investigate the association between antihypertensive prescriptions and incident dementia, using a primary care database. The analysis was based on 575 general and internal practices in Germany (10/2003 - 09/2008) (Disease analyzer database). Antihypertensive medication (ATC codes) during 3 years before newly diagnosed dementia (ICD codes or specific medication) in 1,297 patients was compared to 1,297 controls without dementia after matching for age (mean age: 80.6 ± 8.6 y), sex (females: 62%) and date of diagnosis. Conditional logistic regression was used to calculate crude and adjusted odds ratios (95% confidence intervals). Betablocker prescriptions (≥ 1 per year over 3 y) showed a significant inverse association with newly diagnosed dementia (Odds ratio, OR: 0.79 95% CI 0.61 - 0.99) after adjusting for demographic covariates, health care use, and cardiovascular and neurological comorbidity. In the fully adjusted model, ACE inhibitors also tended to be inversely associated with incident dementia, but failed statistical significance (OR 0.84 95% CI 0.65 - 1.08). Calcium channel blockers were positively related to cognitive impairment only in the crude analysis. The other drug groups were not significantly related to dementia (diuretics OR: 0.89; 0.67 - 1.19; angiotensin- 1-inhibitors OR: 1.04; 0.66 - 1.64). This practice-based case-control study indicated a possible protective effect of some antihypertensive agents (betablockers, ACE-inhibitors) on the development of dementia. Randomized controlled trials are required to confirm this finding.

Biomarkers of Oxidative Stress in Vascular Dementia Patients

Little is known about the role of oxidative stress in the pathogenesis of vascular dementia (VaD). The aim of this study was to investigate the biomarkers of oxidative stress in urine, as reflected by 8-hydroxydeoxyguanosine (8-OHdG), 8-isoprostaglandin F(2a) (8-isoPGF(2a)) and nitrotyrosine (NT) levels, in a group of well characterized VaD patients and in two control groups of Vascular Not Demented (VaND) patients and health y subjects. Ninety-six subjects from the Tianjin municipality in China were recruited. Forty-six patients were in the VaD group, 24 patients with VaND and 26 persons with no signs of cognitive disorder were employed as control groups. Urinary 8-OHdG and 8-isoPGF(2a) was performed using enzyme-linked immunosorbent assay (ELISA), and urinary NT levels were measured by chemiluminescence detection. Significantly higher urinary 8-OHdG levels were detected in VaD patients compared to VaND patients and healthy control subjects. In contrast, urinary 8-isoPGF(2a) levels were significantly lower in VaD patients compared with two control groups. For NT levels, no statistically significant differences were observed among the three groups. Increased urinary 8-OHdG level was a potential marker of oxidative stress in VaD patients. Furthermore, it is also important to take into account potential confounders in order to improve the identification of changes in the status of oxidative stress as related to VaD.

Electroacupuncture Protected Pyramidal Cells in Hippocampal CA1 Region of Vascular Dementia Rats by Inhibiting the Expression of P53 and Noxa

Clinically electroacupuncture (EA) is proved an effective therapy for vascular dementia (VD), but their mechanisms remain uncertain. The aim of this study was to determine whether EA protects pyramidal cells from apoptosis in hippocampus of a VD rat model by inhibiting the expression of p53 and Noxa. One month after a VD animal model was established by bilateral occlusion of common carotid arteries, EA treatment was given at "Baihui" (DU20), "Dazhui" (DU14), and "Shenshu" (BL23). The learning and memory ability was assessed by Morris water maze. Neuronal apoptosis in hippocampus was evaluated with hematoxylin-eosin (HE) staining, and the expression of p53 and Noxa was analyzed by confocal laser scanning microscope with immunofluorescence staining. Expressions of p53 and Noxa in the EA group and sham-operated group were less than in the VD model group (P < 0.01), and the expression of p53 was positively correlated to expression of Noxa in hippocampus of VD rats (r = 0.918, P < 0.01). EA treatment could reduce the amount of apoptotic neurons in hippocampal CA1 area of rats with VD. The average latency in the Morris water maze test was significantly shorter, and escape strategies improved from edge and random searches to more linear swim pathway in the EA group compared with the VD model group (P < 0.01). The increasing expressions of p53 and Noxa play important roles in the pathogenesis of VD. EA improves learning and memory ability and protects pyramidal cells from apoptosis by blocking expression of p53 and Noxa in the hippocampal CA1 region of VD rats. These results suggest a novel mechanism of EA treatment to VD.

Polymorphism C in the Serotonin Transporter Gene in Depression-Free Elderly Patients with Vascular Dementia

Background: Genotypes of the solute carrier family 6 (neurotransmitter transporter, serotonin) member 4 (SLC6A4) have been variously associated with depression, obsessive-compulsive disorder, memory impairment, and anxiety. Less clear are data regarding their association with severe dementia, in particular with vascular dementia (VaD). Aims: To evaluate the possible involvement of different SLC6A4 genotypes/haplotypes in VaD. Methods: The analysis of the 3 markers rs3813034, rs140701 and rs4795541 spanning the SLC6A4 locus was made in 541 consecutive patients clinically diagnosed as having VaD (n = 372) or no cognitive impairment (n = 169) attending a geriatric ward. A community-dwelling sample of 353 healthy subjects, as a reference for the genetic frequencies in the recruitment area, was also included in the study. All patients and subjects were free from any symptoms of depression, obsessive-compulsive disorder and anxiety. A complete neuroimaging documentation was available for all patients. Results: No important differences were observed in genotype distribution across the study groups. Similarly, no important differences were observed in haplotype distribution when a 3-point analysis was made. Conclusion: Our findings suggest that polymorphism C in the promoter region of the SLC6A4 gene plays a minor role, if any, in the pathogenesis of VaD.

Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer's disease

Vascular risk factors have been implicated in the pathogenesis of vascular dementia and Alzheimer's disease. The identification of a novel vascular disease susceptibility locus at 9p21.3 has recently generated great interest. In the present study, we sought to determine whether a common genetic variant (tagged by rs1333049, G/C) in the 9p21.3 locus-that has been previously linked to an increased vascular risk-might influence the susceptibility to vascular dementia (VaD) and late-onset Alzheimer's disease (LOAD). A cohort of 200 VaD patients, 407 LOAD patients and 405 cognitively healthy controls were genotyped for rs1333049 using a fluorogenic 5' nuclease assay. The frequency of the C allele of rs1333049 was significantly higher in VaD (62.2%, P=0.005) and LOAD (60.7%, P=0.004) patients than in controls (53.6%). After adjustment for the APOE ε4 carrier status and other vascular risk factors, the C allele of rs1333049 remained significantly associated with both VaD (OR 1.31, 95% CI 1.07-1.77, P<0.01) and LOAD (OR 1.28, 95% CI 1.04-1.55, P<0.01). Altogether, our data indicate for the first time that the C allele of rs1333049 in the vascular disease susceptibility locus is associated with VaD and LOAD, independent of traditional risk factors and the APOE ε4 genotype.

Association between a Genetic Variant of the Alpha-7 Nicotinic Acetylcholine Receptor Subunit and Four Types of Dementia

We tested the hypothesis whether the partially duplicated variant of α7 nicotinic acetylcholine receptor subunit gene (CHRFAM7A) 2-bp deletion (–2 bp) polymorphism and apolipoprotein E (ApoE) ε4 allele confer susceptibility to Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), Pick’s disease (PiD) and vascular dementia (VD). The study included 175 AD, 35 DLB patients, 38 PiD, 96 VD and 175 healthy control (HC) probands. The CHRFAM7A genotype without the –2 bp allele was significantly over-represented in AD (p = 0.011), DLB (p = 0.001) and PiD (p < 0.0001) compared to HC, but there were no statistical differences in VD (p = 0.407) compared to HC. We confirmed again that the ApoE ε4 allele is a risk factor for dementias. The –2 bp polymorphism of CHRFAM7A can be implicated in AD, DLB and PiD. However, it is unlikely that it plays an important role in the pathogenesis of VD.

Intrathecal synthesis of immunoglobulin G in vascular dementia

Serum and CSF from 53 vascular dementia (VD) patients and 50 controls were analysed to investigate the possibility of an intrathecal synthesis of IgG, defined as an elevated IgG index (greater than or equal to 7) and/or presence of oligoclonal IgG in cerebrospinal fluid (CSF), but not in serum. Five (9%) patients and no controls exhibited an intrathecal synthesis of IgG. The IgG index increased with the degree of dementia (p less than 0.05). It was positively related to presence/absence of hypertension (p less than 0.05) and correlated positively with diastolic blood pressure (p less than 0.05). The findings suggest that immunological factors might be involved in the pathogenesis of VD.