Multi-infarct Dementia Patients Research Articles

Performance on the Rey-Osterrieth complex figure test and the correlation with the magnetic resonance imaging brain lesion volume in multi-infract versus small vessel disease dementia

Background/Aim. Regarding several cognitive domains, including visuospatial and visuoconstructional abilities, little is known about the differences between vascular dementia (VaD) subtypes, even in the most common sub-types, such as multi-infarct dementia (MID) and subcortical ischemic small vessel disease dementia (SSVD). This paper aimed to identify the differences between the performances on the Rey-Osterrieth Complex Figure (ROCF) test in MID and SSVD and correlate the ROCF scores in both groups with magnetic resonance imaging (MRI) ischemic lesion load. Methods. Sixty VaD patients with matching severity of dementia, age, and education were included in this study: 32 with SSVD and 28 with MID ac-cording to the NINDS-AIREN (National Institute of Neuro-logical Disorders and Stroke and Association Internationale pour la Recherch? et l'Enseignement en Neurosciences) neuroradiological criteria. A quantitative scoring system was performed. ROCF was given to all subjects in three test conditions: copy, immediate recall after 3 minutes, and delayed recall after 45 min. Magnetic resonance imaging (MRI) of the is-chemic brain volumes of anterior and posterior lesions, left and right hemispheric lesions, left and right-sided basal ganglia lesions, and total lesion load (TLL) were calculated in both groups. Results. The MID group was more impaired than SSVD on ROCF copy (p = 0.008), immediate recall (p= 0.005) and delayed recall (p = 0.001). There were significant correlations between ROCF copy score and the TLL (p < 0.05) and posterior brain lesion volume (p< 0.05) in the MID group. Conclusion. The importance of visuospatial, visuoconstructional deficit and impairment of visual memory is disregarded in VaD subtypes. These impairments are more severe in MID than SSVD and the deficit of ROCF copying in MID patients correlates with posterior and total MRI lesion volume.

Increased binding to 5-HT1A and 5-HT2A receptors is associated with large vessel infarction and relative preservation of cognition

Vascular dementia accounts for approximately 15-20% of all dementias. In addition, a significant subset of people with Alzheimer's disease have concurrent cerebrovascular disease. Vascular dementia is caused by different cerebrovascular morphological abnormalities including large artery territory infarction (multi-infarct vascular dementia) and sub-cortical ischaemic vascular dementia. Despite this distinction, there is a lack of studies examining the neurochemistry of individual vascular dementia subtypes. Serotonin is believed to play an important role in cognition, and serotonin receptors may provide a novel target for future anti-dementia therapeutics. This study aimed to determine levels of two serotonin receptors in subtypes of vascular dementia and relate any changes to cognition. We have determined, using saturation radioligand binding, the binding parameters (affinity and maximal binding) of ((3)H)-WAY 100635 binding to 5-HT(1A) receptors and ((3)H)-ketanserin binding to 5-HT(2A) receptors in post-mortem tissue from the frontal and temporal cortices of patients with either multi-infarct vascular dementia, sub-cortical ischaemic vascular dementia, mixed Alzheimer's disease/vascular dementia or stroke no dementia (SND). 5-HT(1A) and 5-HT(2A) receptor binding was significantly increased in the temporal cortex of patients with either multi-infarct vascular dementia or SND, compared to age-matched controls. 5-HT(1A) receptor maximal binding in the temporal cortex was also positively correlated with cognition as determined by Mini-Mental State Examination (MMSE) and Cambridge Assessment of Mental Health for the Elderly scores (CAMCOG). These results reveal an important distinction between the neurochemistry of multi-infarct vascular dementia/SND and sub-cortical ischaemic vascular dementia, suggesting that pharmacological manipulation of serotonin offers the possibility to develop novel therapies for stroke and multi-infarct vascular dementia patients. The results also highlight the importance of the cortical 5-HT(1A) receptor in mediating cognition.

Is multi-infarct dementia representative of vascular dementias? A retrospective study

Multi-infarct dementia (MID) indicates a dementia disorder primarily caused by multiple cerebral infarcts. Since other pathogenetic mechanisms cause vascular dementia we evaluated clinical, CT scan and CSF neurochemical parameters of 134 MID and 67 PVD (probable vascular dementia) patients. We found no differences with regard to the presence of major risk factors. Only TIA/stroke episodes and focal neurological signs were significantly more frequent in MID than in PVD cases, an anticipable result on the basis of MID definition. CT scan findings showed a prevalence of subcortical with respect to cortical lesions in both groups, with a higher frequency in MID patients. Subjects with deep infarcts more frequently showed TIA/stroke episodes and diabetes mellitus. No differences were detectable in CSF monoamine metabolite levels. We conclude that in the majority of vascular dementias subcortical damage seems to have a major pathogenetic role.

White matter lucencies in multi-infarct dementia: a somatosensory evoked potentials and CT study

White matter low attenuation (WMLA) on computed tomography (CT) and the central conduction time (CCT) measured by median nerve-somatosensory evoked potentials were examined in 12 multi-infarct dementia (MID) patients, 10 patients with multiple infarcts (MI) without dementia and 11 age-matched controls. Patients with deep vascular lesions without cortical infarcts on CT were included. In MID, prolongation of CCT and moderate to severe WMLA were observed. The CCT and WMLA in MI patients were intermediate. The CCT was longer when the WMLA was more extensive. The result suggests that white matter disease in MID is concerned to the occurrence of dementia by disturbing axonal conduction.

CSF cholinesterase in early-onset and late-onset Alzheimer's disease and multi-infarct dementia of Chinese patients.

Using Ellman spectrophotometric method we measured the total cholinesterase (ChE) activity in lumbar cerebrospinal fluid (CSF) of 13 persons without neurological disorder, 10 non-demented patients with cerebral infarcts, 17 patients with dementia of Alzheimer's type (DAT) (11 presenile, 6 senile cases), 10 patients with multi-infarct dementia (MID), 1 patient with Parkinson's disease associated with dementia. The ChE activity in CSF was significantly lower in the DAT group compared with age-matched control subjects (p < 0.001). This paper also analyses the possibility of using CSF ChE activity as a marker of DAT, and the relationships between its level of activity and the age of the patient at onset, stage of illness and severity of dementia as well as discrepancies in the data published so far. Previous work has shown that ChE activity in the brain tissue and CSF of MID is normal: therefore, if low ChE activity is found in the CSF of MID patients, as was obtained in 8 out of 10 cases in our series, the diagnosis of mixed dementia should be considered.

Childhood conduct problems, stages of Alzheimer's disease, and physical aggression against caregivers

To assess the prevalence of physical aggression against caregivers by Alzheimer's patients. One hundred and ninety-eight individuals with dementia, primarily Alzheimer's disease (AD) were evaluated with the Cohen-Mansfield Agitation Inventory, the Mini Mental Status Examination, two measures of Activities of Daily Living, portions of the Conflict Tactics Scale to measure physical aggression against partner, questions about conduct problems during childhood/adolescence of the patients, and chart records of delusion and paranoia. 25% of the patients engaged in physical aggression against their caregivers in the past year, and 33% of the patients engaged in some act of physical aggression against any individual in the past two weeks. Physical aggression against a caregiver was more likely in the middle (34%) than the early stage of AD (4%). Physical aggression against a partner and agitation were more likely if the patient had a history of symptoms of conduct disorder. Delusions and paranoia were both associated with general physical aggression and general verbal aggression but not physical aggression against a caretaker. 25% of Alzheimer's disease and Multi-Infarct dementia patients engaged in acts of physical aggression against their caregivers. The rate of aggression seen in this clinical sample was much higher than the rate of physical aggression in a community sample of the elderly.

Lower Levels of Eicosapentaenoic Acid and the Ratio of Docosahexaenoic Acid to Arachidonic Acid in Sera of Patients with Multi-Infarct Dementia

To survey the risk factors in multi-infarct dementia (MID), the levels of fatty acids in serum were measured for MID patients and compared with those of healthy individuals. Examined were 40 MID patients aged 57-94 and 152 healthy control subjects aged 50-89. The mean levels of polyunsaturated fatty acid (PUFA), monounsaturated fatty acid and saturated fatty acid of MID were lower than those of the control subjects (p<0.001, respectively). The total amounts of n-3 PUFA and n-6 PUFA in MID were significantly lower than those in control subjects (p<0.01 and p<0.05, respectively) but there were no differences among those of the ratios of n-3/n-6 PUFA. When compared with those of control subjects, low eicosapentaenoic acid (EPA, C20:5n-3) and high arachidonic acid (AA, C20:4n-6) were found in MID (p<0.001, respectively). No significant differences were found in the mean levels of docosahexaenoic acids (DHA, C22:6n-3) between MID and control subjects. The levels of EPA/AA and DHA/AA ratios were lower and the levels of DHA/EPA ratios were higher for the MID than for the control subjects (p<0.001, p<0.01, and p<0.001, respectively). The EPA/AA ratios showed a positive correlation with the DHA/AA ratios in MID patients and control subjects (r=0.65 and r=0.77, p<0.001, respectively). The ratios of DHA/AA showed a positive correlation with the DHA/EPA levels in control subjects (r=0.25, p<0.01), but there was no correlation in the dementia patients. These results suggest that the low EPA and high AA levels and the high DHA/EPA and low DHA/AA ratios might be useful indicators of MID.

The cognitive pattern of vascular dementia and its assessment

Prevailing definitions of dementia are based on the Alzheimer disease (AD) model, which places major emphasis on memory impairment. In other dementias, such as vascular dementia (VaD), several other cognitive dysfunctions predominate over the memory disorder. The cognitive pattern changes according to the type of VaD. In multi-infarct dementia (MID), cortical lesions may cause loss of instrumental functions manifested by aphasia, amnesia, apraxia, or agnosia. Language in MID patients has shorter phrase length, restricted lexical variability, simplified syntax, and low verbal fluency; dysarthria or mechanical impairment of speech with abnormal pitch, melody, or articulation rate also occur. The latter are rare in degenerative dementias. Compared with AD, patients with MID demonstrate superior performance on verbal learning and memory, better delayed recall, and lower rates of forgetting, intrusions, and false positives. Subcortical ischemic dementia, subcortical hemorrhages, or single subcortical strategic infarcts frequently impair executive functions, attention, and speed of information processing; anterograde memory is generally less impaired than in AD patients. The two main problems of batteries used for evaluation of dementia such as those recommended by CERAD (verbal fluency test, a brief naming test such as the Modified Boston Naming Test, free recall of a word list, with immediate and delayed recall, followed by a recognition task of the same words, and line drawings of figures), as well as the Mini-Mental State Examination (MMSE), are (1) their strong emphasis on memory, temporal and spatial orientation, calculation, language, and constructional praxis, and (2) their failure to assess executive functions. Simple tests of executive function include the Trail Making Test, the Wisconsin Card Sorting Test, and the EXIT-25. A simple and effective test is the CLOX, an executive variation of the clock-drawing task. Depressive symptoms and other psychiatric disturbances are particularly common in VaD and become sources of cognitive and functional disability. Several questionnaires assess the neuropsychiatric manifestations of dementia including the Neuro-Psychiatric Inventory (NPI), the BEHAVE-AD test, the Cohen-Mansfield Scale, and the CERAD Behavioral Rating Scale for Dementia. Finally, development of dementia after a stroke may represent true VaD in patients with intact cognition before the stroke, or AD + CVD when the dementia occurs in patients that already had memory problems before the ictus. The diagnosis of VaD is a challenging clinical problem that encompasses the fields of medicine, neurology, psychiatry, and psychology.

Inflammatory markers in Alzheimer's disease and multi-infarct dementia

Inflammation has been involved in the pathogenesis of dementia. The study evaluates the presence and the source of pro- and anti- inflammatory cytokines in the blood of patients with Alzheimer's disease (AD), multi-infarct dementia (MID) or in non-demented elderly people (controls). Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10, IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptor I (sTNF-RI) plasma concentrations and release from blood cells stimulated with lipopolysaccharide (LPS, 1 μg/ml) were determined. The results show that TNF-α released from blood cells is significantly decreased (27%) in all demented patients compared to controls. Circulating TNF-α is increased (400%) only in MID patients. In these patients plasma levels of sTNF-RI are increased (53%) and IL-10 from stimulated blood cells decreased (47%) compared to non-demented subjects. The results show that: (1) peripheral production of TNF-α is blunted in demented (both AD and MID) patients compared to non-demented age-matched subjects; (2) AD patients have a selective disregulation of the peripheral TNF-α system; (3) different cytokines are up- or down- regulated in MID patients showing that in this condition the pro- and anti-inflammatory peripheral cytokine system is more widely affected.

Donepezil (Aricept®) treatment of multi infarct dementia: The caregivers and clinical impression

The purpose of this study was to investigate the clinical and caregivers impression of Aricept ® treatment in patients suffering from Multi-Infarct Dementia (MID). In a prospective study 73 MID patients1 were treated with Donepezil (Aricept®) for 16-to 20-weeks. Donepezil was administered as a 5mg tablet once daily at bedtime. After four weeks, patients tolerant of the 5-mg dose were increased to 10 mg daily. All patients satisfied the DSM-III-R criteria for Multi-Infarct Dementia. 2 After 16-to 20-weeks of treatment, the patient's caregiver completed a questionnaire concerning the effectiveness of the drug. Subjective cognitive improvement, MMSE, 3 ADL4 and IADL5 outcomes were all assessed before and after treatment (referred to as Clinical Impression). Behavioral outcomes evaluated included depression, agitation, violence, anxiety, and paranoid thoughts. Functional and overall family satisfaction were also evaluated. Side effects as well as reasons for discontinuation from the study were also reported. Seventy-three patients participated in the study. Twelve patients (16 percent) terminated participation due to side effects. Total adverse events were reported in 34 (46.5 percent) of patients. Cognitive improvement was reported in 31 (42.4 percent) patients. Verbal skills and attention were the most commonly reported cognitive improvement. Average MMSE declined by 2.6 points after 16-weeks of treatment. No behavioral improvement was reported. Behavioral deterioration was reported in 16 (21.9 percent) of patients. Functional improvement was reported in 32 (42.8 percent) patients. Overall positive family satisfaction was reported in 54 (73.9 percent) patients. Although Donepezil treatment was approved by the FDA for the treatment of Alzheimer's Disease (AD), such treatment for MID patients appears to be a reasonably safe and effective treatment from the caregiver and family's point of view.

Glutamate uptake is decreased in platelets from Alzheimer's disease patients

Because excitotoxicity may be involved in neurodegeneration in Alzheimer's disease, we investigated possible modifications of platelet glutamate uptake in AD patients. High-affinity glutamate uptake was studied in platelets from 35 Alzheimer's disease patients, 10 multi-infarct dementia patients, and 35 age-matched normal controls; it was decreased by 40% in platelets from Alzheimer's disease patients compared with controls and with multi-infarct dementia patients. Platelet glutamate uptake could be used as peripheral marker of glutamatergic involvement and as adjunctive diagnostic tool in Alzheimer's disease patients.

A population-based study of family history in relation to dementia and apolipoprotein E polymorphism in 85-year-olds

We studied a synaptophysin-like immunoreactivity in the hippocampal formation of patients with definite Alzheimer's disease, multi-infarct dementia, patients with no evidence of clinical dementia with neuropathological findings fulfilling the criteria of possible Alzheimer's disease, and age-matched nondemented controls. Possible Alzheimer's disease cases were of special interest because they were considered to represent early Alzheimer's disease. We also studied the spatial relationship of synaptophysin-like immunopositivity with amyloid-β-protein immunopositive senile plaques and anti-paired helical filament immunopositive degenerating neurons locally as well as considering the intrinsic circuits in the hippocampal formation. The synaptophysin-like immunoreactivity was decreased in the hippocampus and the entorhinal cortex in patients with definite and possible Alzheimer's disease but not in multi-infarct dementia patients compared to controls.Equal loss of synapses in possible and definite Alzheimer's disease patients supports the hypothesis that synaptic loss is an early phenomenon in Alzheimer's disease. Unchanged synaptophysin-like immunopositivity in patients with multi-infarct dementia suggests that the loss of synapses is centrally involved in the pathogenesis of Alzheimer's disease and not dementiaper se. There was no spatial correlation between loss of synapses and amyloid-β-protein positive senile plaques. Moreover, we could not find a strict spatial relationship between senile plaques and degenerating neurons. Our results do not support the amyloid cascade hypothesis of Alzheimer's disease that local accumulation of amyloid-β-protein leads to the loss of synapses.

Efficacy and safety of nimodipine in subcortical vascular dementia: a subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial

In Western countries, vascular dementia (VaD) is the most common form of cognitive deterioration after Alzheimer’s disease. Therapeutic trials in VaD have so far failed to yield satisfactory results. One explanation of this failure may be the etiological and clinical heterogeneity of the included patients. Patients with subcortical VaD, defined on a clinical and radiological basis, may constitute a more homogeneous group. Thus, we conducted a post-hoc subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial that evaluated the efficacy and safety of oral nimodipine administered for 6 months in 259 patients. The original patients sample was divided on the basis of head CT in those with subcortical VaD (n=92, 45 nimodipine, 47 placebo) and those with multi-infarct dementia (n=167, 83 nimodipine, 84 placebo). While in the total trial population a treatment effect could not be proved, in this subgroup analysis, the subcortical VaD patients treated with nimodipine performed better on the majority of neuropsychological tests and functional scales in comparison with patients on placebo. No trend could be evidenced in the multi-infarct dementia patients. Treatment efficacy was in particular suggested for the Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency, and for the Instrumental Activities of Daily Living scale. The results did not reach statistical significance in this small sample. Our study preliminarily indicates that nimodipine could be effective in patients with small vessel subcortical VaD and supports the rationale for a further controlled and adequately powered trial to test nimodipine in patients with subcortical VaD.

No association between the intronic presenilin 1 polymorphism and Alzheimer's disease in the Chinese population

Wragg et al. [1996: Lancet 347:509-512] recorded an association between the intron-based presenilin 1 (PS1) genotype 1/1 and late-onset Alzheimer's disease (AD). This study was performed to determine if there is a similar association in the Chinese population. Ninety-one AD cases, 50 multiinfarct dementia (MID) patients, and 73 age-matched normal controls were recruited. Genotyping of PS1 and apolipoprotein E (APOE) was performed by the methods of polymerase chain reaction and restriction fragment length polymorphism. In AD, MID, and normal controls PS1 allele 1 frequency was 0.6703, 0.5600, and 0.6301, respectively; PS1 allele 2 frequency was 0.3297, 0.4400, and 0.3699, respectively. No association was detected between these diseases and any PS1 allele or genotype. There was only a nearly significant negative association between MID and PS1 genotype 1/1 in the subgroup population bearing APOE allele E4 (odds ratio = 0.2753, P = 0.0776). Our results do not support the conclusion that the intronic PS1 polymorphism is associated with Alzheimer's disease.

No association between the intronic presenilin 1 polymorphism and Alzheimer's disease in the Chinese population

Wragg et al. [1996: Lancet 347:509–512] recorded an association between the intron-based presenilin 1 (PS1) genotype 1/1 and late-onset Alzheimer's disease (AD). This study was performed to determine if there is a similar association in the Chinese population. Ninety-one AD cases, 50 multiinfarct dementia (MID) patients, and 73 age-matched normal controls were recruited. Genotyping of PS1 and apolipoprotein E (APOE) was performed by the methods of polymerase chain reaction and restriction fragment length polymorphism. In AD, MID, and normal controls PS1 allele 1 frequency was 0.6703, 0.5600, and 0.6301, respectively; PS1 allele 2 frequency was 0.3297, 0.4400, and 0.3699, respectively. No association was detected between these diseases and any PS1 allele or genotype. There was only a nearly significant negative association between MID and PS1 genotype 1/1 in the subgroup population bearing APOE allele E4 (odds ratio = 0.2753, P = 0.0776). Our results do not support the conclusion that the intronic PS1 polymorphism is associated with Alzheimer's disease. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:1–3, 1999. © 1999 Wiley-Liss, Inc.

EEG coherence in alzheimer and multi-infarct dementia

Summary Previous studies using quantitative EEG (qEEG) absolute and relative power did not reveal significant differences between Alzheimer's dementia (AD) and multi-infarct dementia (MID); several studies have reported differences in qEEG coherence which could be of some diagnostic utility. Aim of this study is to compare EEG coherence in AD and MID in order to evaluate, if topographic changes of coherence could differentiate the two major types of dementia. We examined 61 AD and 41 MID patients. Alpha coherence was significantly decreased in both groups while delta coherence was increased especially in MID patients. However, topographic distribution of coherence alterations were different in the two groups. In fact, the reduction of alpha coherence was diffuse or multifocal in MID and more evident in centro-anterior regions in AD: the increase of delta coherence was diffuse in MID and in the left posterior regions in AD. The decrease of alpha coherence in AD, could be considered an involvement of long cortico-cortical connections and the decrease of alpha coherence in MID, as an involvement of short cortico-cortical connections.

Effects of Aging and Dementia on the Levels of Thiobarbituric-Acid- Reactive Products Stimulated by L-Glutamic Acid in Human Autopsy and Biopsy Brain Tissue

Basal and stimulated (by L-glutamic acid, GA) levels of thiobarbituric-acid-reactive products were estimated in the brain tissue (hippocampus, cortex and cerebellum) from autopsy samples of people with Alzheimer disease (AD), multi-infarct dementia (MID) and from nondemented control patients. The experiment was also performed on biopsy brain tissue (cortex) of nondemented controls. The biopsy brain tissue influenced by normal aging in vivo showed a limited susceptibility to undergo lipid peroxidation stimulated by GA in vitro in comparison with the younger tissue. A significant decrease in the ratio of stimulated to basal levels was found in the cerebellum of MID patients in comparison with nondemented controls and AD patients.

Regional atrophy of the corpus callosum in subjects with Alzheimer's disease and multi-infarct dementia

Regional areas of the corpus callosum (CC) were evaluated in subjects with dementia. The area of the CC and seven distinct subdivisions were measured in subjects with Alzheimer's disease (AD) ( n = 162), multi-infarct dementia (MID) ( n = 28), and in a healthy comparison group ( n = 36). There were significant differences in the regional areas of the CC for both the AD and MID patients relative to values for the comparison subjects. When mildly demented (MMSE ≥ 21), subjects with AD had significantly smaller posterior midbody, isthmus, and splenium and subjects with MID had significantly smaller genu relative to comparison subjects. This study reports different patterns of regional CC area loss in subjects with AD and MID.

Binding of platelet-activating factor to platelets of Alzheimer's disease and multiinfarct Dementia patients

The binding of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor, PAF) to platelets was studied in 22 patients with probable Alzheimer's disease (AD), 11 with multi-infarct dementia (MID), 22 age-matched normal old controls, and 20 young subjects. The results showed a significantly lower degree of PAF binding to platelets of AD and MID patients than in those of the old controls and young subjects (133.3 ± 8.5, and 123.4 ± 16.5 vs. 202.3 ± 11.6 and 206.7 ± 17.3 receptors/cell, respectively; p < 0.01). These differences were due to reduced B max, while K d remained unchanged. No significant difference was observed between the PAF binding to platelets of AD and MID patients nor between that of old and young controls. No correlation was found between age and binding in the various elderly groups. However, a significant correlation was found between PAF binding and degree of cognitive impairment in the AD patients. This is the first evidence to support a possible involvement of PAF in dementing disorders.

Risk of mortality and institutionalization in demented patients with delusions.

Delusions are a common symptom during the course of dementia. Despite their clinical relevance, however, it is still unclear whether they are of prognostic value. This longitudinal study involving, at baseline, 99 demented Alzheimer disease (AD) and multi-infarct dementia (MID) patients, investigates the risk of mortality and institutionalization at 2 years after discharge from a dementia unit in patients with and without delusions at baseline. Results indicate that the presence of delusions is a significant predictor of future institutionalization (odds ratio 3.6, confidence interval 1.3-9.6), even when confounding factors such as age, educational level, and severity of cognitive and functional impairment are statistically controlled. No significant impact on survival was found.