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The present study was designed to assess performance of Alzheimer's (AD) and Multi-infarct (MID) demented patients on the explicit and implicit versions of two memory tasks, namely Word-Stem Completion and Word-Pair Learning. Consistently with previous studies, the AD patients were deficient on the explicit and implicit versions of both tasks. In MID patients, a dissociation emerged between normal implicit and deficient explicit Word-Stem Completion. Two multiple regression analyses were performed to evaluate patients' ability on measures of lexical-semantic competence, explicit memory, and global intellective efficiency in predicting level of repetition priming. The results demonstrate a close association between explicit and implicit memory performance in AD patients but no relation between repetition priming level and measures of lexical-semantic competence or general intelligence. Overall, the results of the present study do not support previous conceptualizations suggesting that a breakdown in the structure of semantic memory is at the root of deficient priming in demented patients. Alternative interpretations of the deficient repetition priming effect in dementia, based on a common mechanism underlying conscious and unconscious retrieval deficits, are discussed.

A long-term follow-up study was performed on patients with transient global amnesia (TGA) in order to evaluate the prognosis, the recurrence rate and the occurrence of stroke and dementia. 102 patients (57 women, 45 men; mean age 62.8 +/- 9.4 years) were prospectively included and followed up. The follow-up duration ranged between 12 and 241 months with an average value of 82.2 +/- 51.1 (mean +/- SD). The death rate showed no difference from that of sex- and age-matched subjects. TGA recurred in 19 cases (18.63%). Only 4 patients suffered subsequent stroke, and only 3 showed intellectual deterioration. TGA prognosis was shown to be better than that of RIA and lacunar patients.

We investigated whether MCI patients with hippocampal atrophy or multiple subcortical infarcts demonstrate neuropsychological patterns and markers considered typical of Alzheimer's disease (AD) and of vascular dementia (VD), respectively. An extensive neuropsychological battery, including tests of memory, visual-spatial and executive functions, language, attention, praxis and psychomotor speed, was administered to 36 mild cognitive impairment (MCI) patients with hippocampal atrophy and 41 MCI patients with multiple subcortical infarcts. Both groups of MCI patients were very mildly impaired and well matched in terms of MMSE scores. A clear, disproportionately severe, episodic memory disorder was observed in MCI patients with hippocampal atrophy. A less specific neuropsychological profile, consisting of impairment on an Action Naming task that is sensitive to frontal lobe lesions, was observed in MCI patients with multiple subcortical infarcts. In MCI patients, a disproportionately severe episodic memory impairment strongly points to an Alzheimer's type brain pathology, whereas the prevalence of executive deficits and other frontal lobe symptoms are a much weaker diagnostic marker of small vessel subcortical disease. (JINS, 2008, 14, 611–619.)

Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is considered a cerebrovascular disorder with almost exclusively neurological symptoms, arteriopathy is generalized and also involves the choroid and retina.To study optic nerve head microvascular function in CADASIL by assessing blood flow, volume, and velocity with a retina flowmeter.Scanning laser Doppler flowmetry permits the noninvasive assessment of relative blood velocity, volume, and flow in a sample volume of either retina or anterior optic nerve head. Measurements were performed in a first group of 9 eyes of 5 patients with CADASIL and a second group of 8 eyes of 4 healthy subjects. Hemodynamic parameters were computed in 4 quadrants of the optic disc (superior nasal, superior temporal, inferior nasal, and inferior temporal). The Wilcoxon rank sum test was used to assess differences in relative flow, volume, and velocity in each quadrant and between the 2 groups and differences in overall optic nerve head blood flow, volume, and velocity.Patients with CADASIL had a significant decrease in overall blood flow and volume compared with healthy subjects (P.05). The reduction in blood flow and volume was particularly significant in the superior and inferior temporal quadrants. No significant differences were found nasally between the patients and the control groups.Our results suggest that hemodynamic parameters are abnormal in the superficial nerve fiber layer of the optic nerve head of patients with CADASIL, especially in the temporal quadrants of the neuroretinal rim.

Objectives – To examine differences in cerebrovascular reactivity between multi-infarct and Alzheimer types of dementia. Patients and methods – Using transcranial Doppler, measurements of flow velocity in the middle cerebral arteries during apnea, thumb-to-finger opposition and verbal and design discrimination tasks were recorded in patients with multi-infarct (n = 10; mean age 68 + 7.5 years) and Alzheimer types of dementia (n = 10; mean age 62±9.1 years). Controls were 20 healthy subjects matched for age and sex. Results – Cerebral reactivity to apnea was significantly lower (P

Peripheral blood mononuclear cells (PBMC) from 40 consecutive patients entering a screening program on cognitive impairment were studied in vitro with respect to their sensitivity to dexamethasone (DEX). Phytohemagglutinin-induced proliferation by PBMC from patients with senile dementia of the Alzheimer type (SDAT) was less sensitive to the inhibitory effect of DEX, compared to PBMC from patients with multi-infarct dementia (MID) and PBMC from patients with miscellaneous causes of cognitive impairment (MISC). An intermediate sensitivity was found with PBMC from patients with clinical signs of both MID and SDAT (= MIXED). These differences could not be explained by differences in the composition of the CD4+ T cell population, interleukin (IL)-2 or IL-4 production, or quantitative differences in the expression of glucocorticoid receptors as measured by flowcytometry. However, the expression of bcl-2 was higher in PBMC from SDAT patients than in cells from MID patients or from MISC patients, whereas the MIXED group showed an intermediate expression; a high bcl-2 expression correlated with a low DEX-sensitivity. These findings suggest that characteristics of PBMC reflect related changes in the central nervous system and indicate that PBMC may be a useful and accessible tool to obtain more insight into the pathogenesis of Alzheimer's disease. Chemicals/CAS: dexamethasone receptor; Dexamethasone, 50-02-2; Immunosuppressive Agents; Interleukin-2; Interleukin-4, 207137-56-2; Phytohemagglutinins; Proto-Oncogene Proteins c-bcl-2; Receptors, Glucocorticoid

This study aimed to explore verbal and spatial memory spans in Alzheimer's (AD) and multi-infarct (MID) demented patients. For this purpose, we administered the forward and backward versions of the Digit Span and of the Corsi test to 18 AD, 18 MID and 26 controls. Results revealed a normal forward verbal span but reduced backward verbal and forward and backward spatial spans in both demented groups. These data are discussed in the light of the Working Memory model. It is argued that the normal verbal forward span is sustained by a normally functioning Articulatory Loop. The deficient processing resources of the Central Executive, on the other side, are responsible for the reduced extension of the other memory spans. The possible anatomical substrate of short-term memory impairment in dementia, as well as alternative interpretations of memory span performance in demented patients are discussed.

In this study we explored the rate of forgetting from long-term memory in Alzheimer's (AD) and multi-infarct (MID) dementia. For this purpose, we administered to 15 AD, 15 MID, and 22 control subjects two tasks exploring, respectively, long-term verbal and long-term visuo-spatial memory. The absolute rate of forgetting in both tasks was computed as the difference between immediate and delayed recall of memorandum. Since level of immediate recall was significantly different between groups, a proportional rate of forgetting (percentage of memorandum lost passing from immediate to delayed recall) was computed for each patient. In the verbal task (Rey's 15 words) AD patients displayed significantly larger absolute and proportional rates of forgetting than MID and control subjects. In the spatial task (Corsi block supraspan), the absolute rate of forgetting was only marginally different between groups. Nevertheless, AD patients demonstrated a larger proportional rate of forgetting than MID and normal subjects. These results point out an exalted decay of information from long-term memory store in AD patients. In the light of previous data (Corkin et al., 1984; Kopelman, 1985) we propose that long-term memory deficits in AD is due, at least in part, to an abnormal forgetting of information within the first few minutes following acquisition. Information still present in the subsequent period (10 min to several days) is retained normally. The normal rate of forgetting in MID patients, further, suggests different mechanisms underlying memory disorders in vascular and degenerative dementias.

Albumin and IgG were determined in serum and cerebrospinal fluid (CSF) of patients with early-onset Alzheimer's disease (AD, n. 13), senile dementia of Alzheimer type (SDAT, n. 33), vascular dementia divided into multi-infarct (MID, n. 9) and probable vascular (PVD, n. 11) dementia. Albumin and IgG ratio and IgG index were calculated. CSF albumin and albumin ratio were significantly higher in MID patients indicating an increased BBB permeability. IgG ratio and IgG index did not show any significant difference among groups. These results do not provide evidence for BBB damage in AD/SDAT, while in MID the increase of CSF albumin and albumin ratio is suggestive of BBB dysfunction.

Thirty-four demented patients, 19 with Alzheimer's and 15 with multi-infarct dementia, were studied using single photon emission computed tomography, and 99mTc-hexamethyl-propylenemine oxime as a tracer of regional cerebral perfusion. Tracer activity ratios, determined in cortical and subcortical regions, were compared with those of 11 age-matched controls. In both groups of demented patients, most of the cortical regions showed significant declines in tracer uptake from control values, with the greatest reductions in the parietal cortex. Significantly lower parietal indexes were found in the Alzheimer's patient group as compared both to the control values and to the group of multi-infarct dementia patients. A positive correlation was found between the magnitude of the parietal deficits and the severity of dementia.

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.

The cognitive and behavioral effects of oxiracetam therapy during long-term treatment in patients with dementia of Alzheimer type (DAT) and multi-infarct dementia (MID) were studied in comparison with a historical control group. Twenty DAT/MID outpatients, aged 54-86 years, received oxiracetam (800 mg twice a day) for a period of 6 months. Another 20 DAT/MID outpatients, aged 67-85 years, were selected from our clinical records in order to obtain a control group of patients matched for age, sex, diagnosis, baseline Mini Mental State Examination (MMSE) score and follow-up duration. All the patients were diagnosed as having mild to moderate degrees of dementia as defined by a baseline MMSE score between 14 and 24. The patients of both groups underwent, both at baseline and after 6 months, the following neuropsychological tests: MMSE, Idiopathic Cerebral Dysfunction Scale, Babcock Test, Gibson Spiral, Toulouse-Pieron Test. Statistical analysis of experimental data demonstrated that at baseline the two groups were comparable. At the end of the study period the oxiracetam group scored significantly better on the majority of the tests evaluating memory, attention, orientation, concentration and psychomotricity than the control group, in which a worsening trend was seen on the whole. No side effects were seen during oxiracetam treatment. The present study, showing positive clinical findings after long-term oxiracetam therapy in controlled conditions, confirms that this drug can be a useful pharmacological treatment for mild to moderate degrees of dementia.