bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Assessment of Synaptic Density in the Outer Molecular Layer of the Hippocampal Dentate Gyrus in Alzheimer's Disease
Authors: Scheff Stephen , Sparks D. Larry , Price Douglas
Published: August 2007

We quantified the synaptic density in the outer molecular layer of the hippocampal dentate gyrus. Autopsy material from 9 individuals with Alzheimer disease (AD) were compared to 10 age-matched, postmortem-matched controls without dementia, using standard electron microscopy. Statistical analyses showed a significant change in the density of synapses between controls and AD subjects. There was a significant decline in the width of the entire molecular layer in the AD material. Synaptic density showed a significant correlation with synaptic apposition length in both AD and control groups. As the number of synapses declined, the synaptic apposition length increased. The decline in density of synapses in the AD group might reflect the degree of neuronal loss in the entorhinal cortex. Such a loss in synaptic connectivity could play a key role in memory-related problems associated with AD.
Letter and Category Fluency in Alzheimer's Disease: A Prognostic Indicator of Progression?
Authors: Coen Robert.F , Maguire Conor , Swanwick Gregory R. , Kirby Michael , Burke Teresa , Lawlor Brian , Walsh J. Bernard , Coakley Davis
Published: August 2007

This study investigated differential patterns of performance by 40 Alzheimer''s disease (AD) patients on standardised letter and category fluency tests. The performance of 24 age and education matched controls was used to classify patients as relatively more letter fluency impaired (L<C, n = 15) or more category fluency impaired (C<L, n = 25), and clinical features distinguishing these patient subgroups were investigated. Category performance was equally impaired in both patient subgroups, whereas the L<C subgroups were particularly impaired on letter fluency. The subgroups differed significantly in duration of illness (24 months for L<C group, 47 months for C<L group; t = 2.69, p = 0.01) but did not differ in global dementia severity, age, education; general language ability, or functional status. Data on annual rate of change (ARC) on the Mini-Mental State Examination were available for 26 patients. While not statistically significant, subgroup ARC differences were suggestive of more rapid decline in the L<C patients, consistent with the finding of shorter duration of illness in this group. Word fluency tests may have potential as early predictors of rate of progression in AD.
An Enriched-Population, Double-Blind, Placebo-Controlled, Crossover Study of Tacrine and Lecithin in Alzheimer's Disease
Authors: Foster Norman L. , Peterson Ronald C. , Gracon Stephen I. , Lewis Karen
Published: August 2007

We studied the effects of 40 and 80 mg/day of tacrine on patients with probable Alzheimer''s disease (AD) in an 8-week, randomized, double-blind, placebo-controlled crossover trial with an enriched-population design. In the initial dose titration phases an intent-to-treat analysis showed significantly more improvement with 80 mg/day of tacrine than placebo. In the subsequent crossover trial that included only ‘responders’, no significant improvement was observed with tacrine, whether or not it was given with lecithin. We found that individualized dose titration and enrichment strategies were not helpful and had the effect of reducing the power of the study. In the dose titration phase of this study we found that more impaired subjects were as likely to improve as those who were less impaired, suggesting that tacrine should be further investigated in more severely demented AD patients.
Glial Fibrillary Acidic Protein in the Cerebrospinal Fluid of Patients with Dementia
Authors: Wallin Anders , Blennow Kaj , Rosengren Lars E.
Published: August 2007

Glial fibrillary acidic protein (GFAP) is the structural protein of the astroglial intermediate filament that forms the morphological basis of astrogliosis. In the present study, GFAP concentrations in cerebrospinal fluid were measured in patients with various dementia diseases. A significant correlation between GFAP and age was found both in the total dementia group and in the controls. Covariance analysis with GFAP as dependent variable and age and albumin ratio as covariates followed by multiple group comparisons showed that, with regard to GFAP levels, the controls (n = 39) differed significantly from the patients with vascular dementia (n = 20; p < 0.05), senile dementia of the Alzheimer type (n = 29; p < 0.05), and ''pure'' Alzheimers disease (n = 8; p < 0.05), but not from those with frontal lobe dementia (n = 5).
Sleep-Related Breathing and Movement Disorders in Healthy Elderly and Demented Subjects
Authors: Bader Gaby G. , Turesson Kent , Wallin Anders
Published: August 2007

Reported findings regarding sleep and sleep disorders in the elderly often conflict. Differences in results across studies may arise from selection of subjects, definitions and recording conditions. Our purpose was to test a method to study elderly, both healthy and demented, under the most natural conditions, without disturbing a fragile sleep. Using clinical parameters and a non-disturbing recording method, we evaluated sleep quality in patients with carefully diagnosed dementia and compared the results to a group of healthy subjects between 50 and 70 years of age. Healthy subjects awoke less and had more quiet sleep than patients, while in patients a tendency for delayed sleep latency and more active sleep was observed. Consistent with previous investigations, sleep-related respiratory disorders (SRRD) were more common in patients than in the matched control group, and periodic breathing appeared only among patients. SRRD, of both obstructive and central types, were only mild, with periodic breathing dominating only among patients. Most of the desaturations were less than 10%. We did not observe respiration of the Cheyne-Stokes type. Patients had more sleep-related movement disorders (SRMD), particularly with increase of twitches and long movements. Periodic movements were not significantly increased among the patients. The method, and the data obtained may be useful for practitioners dealing with sleep disorders in geriatric populations. In the elderly, interactivity between sleep, SRRD and SRMD may be bidirectional and as elderly and demented subjects might have a distorted homeostatic sleep response, SRRD and SRMD, even in a mild form, may cause sleep disruption and worsen dementia.
The Efficacy and Safety of Donepezil in Patients with Alzheimer's Disease: Results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Rogers Sharon L. , Friedhoff Lawrence T.
Published: August 2007

This study evaluated the efficacy and safety of donepezil in patients with mild to moderately severe Alzheimer''s disease, and examined the relationships between plasma donepezil concentration, red blood cell acetylcholinesterase (AChE) activity and clinical response. The trial was of a multicenter, double-blind, parallel-group design and patients were randomised to once-daily treatment with either donepezil (1, 3 or 5 mg) or placebo. The 12-week double-blind phase was followed by a 2-week single-blind placebo washout. 161 patients (55-85 years of age) entered the study and 141 completed treatment. Patients treated with donepezil showed dose-related improvements in the Alzheimer''s Disease Assessment Scale - cognitive subscale score (ADAS-cog) and in MMSE scores. The improvements in ADAS-cog were statistically significantly greater with donepezil 5 mg/day than with placebo. There was a 50% reduction in the percentage of patients showing clinical decline with donepezil at 5 mg/day (11%) relative to placebo (20%). In addition, a statistically significant correlation between plasma concentrations of donepezil and AChE inhibition was demonstrated. A plateau of inhibition (76-84%) was reached at plasma donepezil concentrations >50 ng/ml. The correlation between plasma drug concentrations and ADAS-cog (p = 0.014), MMSE (p = 0.023) and patient quality of life scores, assessed by the patient (p = 0.037) were also statistically significant, as was the correlation between AChE inhibition and change in ADAS-cog (p = 0.008). The incidence of treatment-emergent adverse events with all three dosages of donepezil (64-68%) was comparable to that observed with placebo (65%). Donepezil had no clinically significant effect on vital signs, haematology or clinical biochemistry tests. Importantly, donepezil was not associated with any hepatotoxicity, as observed with acridine-based cholinesterase inhibitors.
Symptoms and Signs in Dementia Synergy and Antagonism
Authors: Graham Janice E. , Mitnitski Arnold B. , Mogilner Alexander J. , Gauvreau Denis , Rockwood Kenneth
Published: August 2007

This paper addresses the synergy and antagonism between symptoms and signs among 2,914 elderly Canadians diagnosed in 15 categories, including no cognitive impairment, cognitive impairment but no dementia, mild, moderate and severe forms of Alzheimer''s disease and vascular dementia, 4 subtypes of possible Alzheimer''s disease, Parkinson''s dementia, unspecified other dementias and unclassified dementias. Attention is paid to the relationships between symptoms and signs rather than conventional analyses which assume independent signs. We demonstrate that dementia progression and specific aetiologies have characteristic patterns of decline and destruction from the strong synergy that exists between symptoms and signs among the population with no cognitive impairment. These findings have potential implications for the incorporation of new diagnostic criteria into existing databases.
The Gain of Apolipoprotein E Genotyping to Separate Patients with Alzheimer's Disease from Normal Individuals: Relevance to Community Studies
Authors: Frisoni Giovanni B. , Geroldi Cristina , Bianchetti Angelo , Binetti Giuliani , Trabucchi Marco
Published: August 2007

Neuropsychological screening tests such as the Mini Mental State Examination (MMSE) are commonly used for case finding in community studies on dementia or Alzheimer''s disease (AD). However, the high proportion of false-positives is an important limitation to the feasibility of such studies. The aim of this study was to evaluate whether adding apolipoprotein E (apoE) genotyping to the MMSE is followed by a significant reduction of the false-positive rate. Subjects were 70 AD patients (MMSE 13-28) and 70 normal controls (MMSE 25-30). Multivariable discriminant analysis was used to classify subjects on the basis of age, gender, MMSE score and the presence of the Ε4 allele of apoE. When sensitivity was set at 99%, the model including age, gender and MMSE had a false-positive rate of 13.5%, while adding Ε4 to the previous variables decreased this figure to 6.7%. In a hypothetical community study screening for AD in a population of 1,000,000, this would turn in a decrease of false-positives from about 19,000 to about 9,500. We conclude that the use of apoE genotyping in community case-finding studies is promising and should deserve further consideration.
Enhanced Cytotoxic Response of Natural Killer Cells to lnterleukin-2 in Alzheimer's Disease
Authors: Solerte Sebastiano Bruno , Fioravanti Marisa , Severgnini Silvia , Locatelli Mattia , Renzullo Maria , Pezza Nunziata , Cerutti Nadia , Ferrari Ettore
Published: August 2007

Experimental data suggest an involvement of immune cellular components in the development of Alzheimer''s disease (AD). Against this background, the spontaneous natural killer (NK) cell activity and the NK-induced cytotoxicity after interleukin-2 (IL-2) were studied in healthy elderly subjects and in patients with dementia of Alzheimer type (SDAT) and multi-infarct type (MID). Higher NK cytotoxicity (expressed as total lysis and percent increase) at different IL-2 concentrations (50 and 100 IU/ml/cells) was demonstrated in patients with SDAT than in healthy elderly subjects (p < 0.001) and MID patients (p < 0.001). NK cell activity of MID patients was similar to that of healthy elderly and healthy young subjects. A negative correlation between the percent increase in NK cytotoxicity after IL-2 and the Mini Mental State Examination Score was also found in SDAT patients (p < 0.01). Alterations of IL-2-mediated NK cytotoxicity may therefore support the neuroimmune hypothesis of AD.
Cell-Cycle-Dependent Abnormal Calcium Response in Fibroblasts from Patients with Familial Alzheimer's Disease
Authors: Tatebayashi Yoshitaka , Takeda Masatoshi , Kashiwagi Yuziro , Okochi Masayasu , Kurumadani Takahiro , Sekiyama Atsuo , Kanayama Gen , Hariguchi Shiro , Nishimura Tsuyoshi
Published: August 2007

Change in calcium response was studied to clarify the pathological process of Alzheimer''s disease (AD). Cultured fibroblasts from patients with familial Alzheimer''s disease (FAD; n = 6), sporadic Alzheimer’s disease (SAD; n = 4), and age-matched healthy control subjects (n = 4) were studied with an ACAS Interactive Laser Cytometer (ACAS-470). Fibroblasts from two independent families with FAD (OS-1, and OS-2 families) showed a suppressed calcium response after stimulation by 100 nM bradykinin (BK) 100 nM Vasopressin (VP)or 10% FCS in Ca2+-free condition compared with control fibroblasts at 48 h after plating. However, on the 7th day after plating, the abnormal calcium response was no longer observed. The height of the calcium peak showed periodic variation, indicating a relationship of calcium response with the cell cycle. When fibroblasts from OS-1 and OS-2 families were arrested in S phase, they showed a significantly suppressed calcium peak after BK stimulation. However, when those fibroblasts were arrested in other phases, they showed the same calcium peak as the other cells. The suppression of calcium response in S phase was indistinguishable from the calcium suppression induced by A23187 administration. Since Hardy type mutation on amyIoid precursor protein gene is found in the OS-1 family, the observed abnormalities in calcium response might be related with pathological processing of amyloid precursor protein in AD. The reported abnormal calcium response, which is observed most obviously in fibroblasts in S phase, may indicate participation of the cell-cycle-dependent process in the pathology of AD.
Relative Roles of Plaques and Tangles in the Dementia of Alzheimer's Disease: Correlations Using Three Sets of Neuropathological Criteria
Authors: Nagy Z. , Esiri M.M. , Jobst K.A. , Morris J.H. , King E.M.-F. , McDonald B. , Litchfield S. , Smith A. , Barnetson L. , Smith A.D.
Published: August 2007

We have performed a quantitative analysis of the amyloid load (plaques), neuritic plaques and neurofibrillary tangles (NFT) in the frontal, temporal and parietal association cortices of autopsied brains from 49 prospectively evaluated patients with Alzheimer''s disease (AD) diagnosed according to three sets of published pathological criteria. These patients had been assessed clinically with psychological testing of cognitive abilities within 6 months of death. Correlations were sought between severity of pathological change and cognitive status before death, duration of disease and age at death. Using Khachaturian and CERAD criteria highly positive correlations were obtained between the extent of cognitive deficit and the density of NFT in frontal and parietal lobes. The percentage area of cortex occupied by amyloid in the parietal lobe was correlated to the cognitive deficit only in the CERAD-diagnosed cases. The density of all amyloid plaques (AP) showed no correlation with the extent of cognitive deficit, but the densities of neuritic plaques did correlate with cognitive deficit. Both amyloid load and tangle densities were positively correlated with disease duration. All these correlations were reduced or absent in a sub-group of cases fulfilling the Tierney et al. A3 diagnostic criteria for AD. We found no pathological measure that correlated with the age of patients at death. Amyloid loads and NFT densities showed highly significant but selective positive correlations, the most striking being between temporal lobe NFT density and frontal and parietal lobe amyloid load and between temporal lobe NFT density and frontal and parietal lobe NFT densities. Correlations involving AP density as a measure of amyloid load were almost always less significant than those involving the percentage area of cortex occupied by amyloid, suggesting that the latter measures amyloid load more accurately. However, the highest correlations of NFT densities were with neuritic plaque densities. Overall this study highlights the relevance of neuritic changes (revealed by NFT and neuritic plaques) and the irrelevance of amyloid plaques to the dementia of AD.
Visuospatial Performance in Very Old Demented Persons: An Individual Difference Analysis
Authors: Hill Robert D. , Bäckman Lars , Wahlin Åke , Winblad Bengt
Published: August 2007

This study examines selected demographic, psychometric, and biological measures as predictors of visuospatial performance in a sample of 98 persons with mild to moderate dementia. Visuospatial performance was measured using standardized neuropsychology instruments, namely: Poppelreuter''s figures, the clock test, and block design. Although multiple measures were initially correlated with performance on the selected visuospatial tests, the Mini-Mental State Examination was the exclusive predictor of Poppelreuter''s figures and the clock test scores. For block design, years of education also contributed to the prediction model, but only among mildly demented persons. These results suggest that disease severity plays a dominant role in the prediction of visuospatial performance in dementia, particularly in more advanced stages of the disease. The differential role of education in predicting block design performance in mild vs. moderate dementia was also highlighted.
Amyloid Precursor Protein Accumulation in Lewy Body Dementia and Alzheimers Disease
Authors: Van Gool D. , De Strooper B. , Van Leuven F. , Dom R.
Published: August 2007

The presence of amyloid precursor protein (APP) and β-amyloid protein (βA4) was investigated in the cerebra of 4 patients with Alzheimers disease (AD), 1 patient with Down''s Syndrome, 4 patients with dementia of the Lewy body type (DLB) and 4 age-matched, clinically nondemented controls, of which one displayed many amyloid plaques. The different types of amyloid plaques stained strongly with antibodies against βA4. Antibodies against the C-terminal region of APP reacted only weakly with small swollen neurites and with globular deposits in neuritic-type plaques from patients with AD. The antibody against the N-terminal region of APP stained strongly cellular elements in the neuritic type plaques of patients with AD but not dense cored plaques. In contrast, patients with DLB displayed with this antibody a homo-geneous staining of dense cored amyloid plaques. Some Lewy bodies stained with the antibody against the N-terminal region of APP as well. These results indicate that the processing of APP in AD and DLB could be different, to yield different fragments deposited in AD and DLB amyloid plaques.
Diagnosis of Dementias Using Partial Least Squares Discriminant Analysis
Authors: Gottfries Johan , Blennow Kaj , Wallin Anders , Gottfries C.G.
Published: August 2007

Twenty patients with Alzheimers disease (AD), 34 with senile dementia of the Alzheimer type (SDAT) and 12 with vascular dementia (VAD) were carefully investigated. The diagnoses were made according to the DSM-III-R criteria and for AD/SDAT also according to the NINCDS-ADRDA criteria. The data set consisted of 29 descriptor variables obtained at the examination, and the data were fitted to a partial least squares model using dummy variables for the response variables (i.e. clinical diagnoses). The distribution of the scores over the descriptor variable space revealed adequate classification regarding all three diagnoses, with some overlap between SDAT and AD and between VAD and SDAT. The study demonstrates a clear difference in symptomatology between AD and SDAT with no influence of age per se or the severity of dementia.
Quality of Life in Alzheimer’s Disease
Authors: Howard Kellee , Rockwood Kenneth
Published: August 2007

We reviewed and independently ranked the measurement properties of quality of life (QL) instruments currently used in antidementia drug trials for Alzheimer''s disease. Of 36 read reports, 5 measured and 4 mentioned QL. Eight instruments, labelled QL measures, included questionnaires measuring function, self-rating instruments measuring the caregivers'' impression of the impact of sickness and deterioration of memory, and observational rating scales measuring function. The most thoroughly tested QL measure was the Progressive Deterioration Scale. The instruments with the most promising measurement properties were the Progressive Deterioration Scale and the Italian Quality of Life Scale. Most instruments now used to assess QL in anti-dementia drug trials have not been adequately validated in patients with Alzheimer''s disease. Effort should be directed both to conceptual and practical development in the assessment of QL in dementia.
Beta-Amyloid Deposition in the Medial Temporal Lobe in Elderly Non-Demented Brains and in Alzheimer’s Disease
Authors: Armstrong R.A.
Published: August 2007

The density of diffuse, primitive, classic and compact β-amyloid (β/A4) deposits was estimated in the medial temporal lobe in elderly non-demented brains and in Alzheimer''s disease (AD). In the non-demented cases, β/A4 deposits were absent in the hippocampus but in 8/14 cases they were present in the adjacent cortical regions. Variation in β/A4 deposition in the non-demented cases was large and overlapped with that of the AD cases. The ratio of mature to diffuse β/A4 deposits was greater in the non-demented than in the AD cases. In both the non-demented cases and AD, the β/A4 deposits were clustered with, in many tissues, a regular distribution of clusters along the cortex parallel to the pia. However, the mean cluster size of the deposits in the cortex was greater in AD than in the non-demented cases. These results suggest that the spread of β/A4 pathology between the modular units of the cortex and into the hippocampus could be important factors in the development of AD.
Alzheimer Disease Amyloid Proteins Inhibit Brain Endothelial Cell Proliferation in vitro
Authors: Grammas Paula , Botchlet Toya , Fugate Robert , Ball Melvyn J. , Roher Alex E.
Published: August 2007

Despite the close morphological association of β-amyloid and vascular cells, the functional effects of amyloid in cerebral endothelial cells in Alzheimer’s disease have not been assessed. In this study, effects of amyloid fractions purified from senile plaques of AD brains were compared to synthetic amyloid peptides for their ability to affect brain endothelial cells in vitro. Our results indicate that plaque-derived amyloid inhibit brain endothelial cell proliferation in vitro by 40%. This inhibition was specific for plaque-derived amyloid, was not evoked by synthetic Aβ1–40, and was not mediated by alterations in intracellular calcium levels. Amyloid fractions from AD brains, although not directly toxic to brain endothelial cells, inhibit endothelial replication in vitro and therefore could alter the ability of vessels to repair and regenerate after injury.
Clinical Diagnosis of Frontal Lobe Dementia and Alzheimer’s Disease Relation to Cerebral Perfusion, Brain Atrophy and Electroencephalography
Authors: Julin Per , Wahlund Lars-Olof , Basun Hans , Persson Anders , Måre Klas , Rudberg Ulf
Published: August 2007

The regional cerebral blood flow, brain atrophy, white matter changes and neurophysiologic changes were evaluated in 28 patients with a clinical diagnosis of probable Alzheimer''s disease (AD) and in 8 patients with a clinical diagnosis of frontal lobe dementia (FLD) using single photon emission computed tomography, magnetic resonance imaging and electroencephalography (EEG). We found that FLD patients had more severe frontal blood flow reduction and less severe parietal blood flow reduction compared to AD patients. Among patients with mild dementia the EEG changes were less severe in the FLD group. No significant differences were found in white matter changes or in regional atrophy.
Quantitative EEG Mapping, Regional Cerebral Blood Flow, and Neuropsychological Function in Alzheimer’s Disease
Authors: Passero Stefano , Rocchi Raffaele , Vatti Giampaolo , Burgalassi Laura , Battistini Noè
Published: August 2007

The relations between quantitative EEG, regional cerebral blood flow (rCBF), severity of disease and neuropsychological data were analyzed in 31 patients in different stages of Alzheimer’s disease (AD). As a group the demented patients had higher delta and theta activities, lower alpha activity and lower alpha peak frequency than control subjects. rCBF was reduced in all regions studied but mainly in the temporoparietal areas. An analysis of correlations showed a close relationship between rCBF and certain quantitative EEG Parameters in AD patients, mainly the power of the theta and delta bands. Both rCBF evaluation and quantitative EEG provide functional information related to the severity of cognitive impairment.
Neuropathological Analysis of Dementia in a Japanese Leprosarium
Authors: Goto Masamichi , Kimura Takemi , Hagio Satoru , Ueda Keishi , Kitajima Shin-ichi , Tokunaga Hidetsugu , Sato Eiichi
Published: August 2007

In a neuropathological study of consecutive autopsies, prevalence and cause of dementia in a Japanese leprosarium were investigated, where more than 95% of inpatients with a mean age of 70 years are now free from active leprosy. In 10 years (1983–1992), clinically overt dementia at death was 35/136 (25.7%) in the age group over 65 years (mean age 79.4). Autopsy was performed in 85 cases (mean age 81 years), and clinically overt dementia was seen in 25 subjects (29.4%). Neuropathologically, Alzheimer''s disease (AD) was seen in 9 cases (10.6%), vascular dementia (VD) in 9 cases (10.6%), mixed type in 3 cases (3.5%) and unclassified in 4 cases (4.7%). In the age group of 65-84 years, AD was 5/58 (8.6%), VD was 4/58 (6.9%), mixed type was 2/58 (3.4%), and unclassified was 1/58 (1.7%). Compared with previous Japanese general population-based data, where VD was more frequent than AD, the rate of dementia in our leprosarium was high, and pathologically confirmed AD was as common as VD. Recently, a prophylactic effect of the antileprosy and anti-inflammatory drug DDS (dapsone, 4,4´-diaminodiphenyl sulfone) has been suggested. Lepromatous patients take more DDS (51.9%) than tuberculoid patients (11.5%), however, as the dementia rate of tuberculoid leprosy (17.9%) in those 65–84 years old is similar to lepromatous leprosy (15.9%) in our study, we do not support their viewpoint.
Severity of Dementia Correlates with Loss of Broad-Band Visual Cortical Responses
Authors: Politoff Alberto L. , Monson Nancy , Stadter Richard P. , Hass Patricia
Published: August 2007

We have shown that the response to flash stimulation of the occipital electroencephalogram (EEG) in Alzheimer disease (AD) patients is smaller than in normal subjects. To ascertain whether this is a specific feature of AD or a nonspecific effect of dementia, we investigated in AD and multi-infarct dementia (MID) patients the relationship between cognitive function, measured as Mini-Mental State Examination score, and EEG power response, measured as the difference in spectral power between flash-stimulated EEG and resting EEG. Both variables were positively correlated and the regression equations of AD and MID patients were not significantly different, showing nonspecificity. The coupling between cognitive function and power response is discussed in relation to the dynamic binding hypothesis of cognition.
Procedural Memory and Parkinson's Disease
Authors: Allain Hervé , Lieury Alain , Quemener Véronique , Thomas Véronique , Reymann Jean-Michel , Gandon Jean-Marc
Published: August 2007

A detailed analysis of the mnestic deficits associated with Parkinson''s disease (PD) contributes to explaining the cognitive disorders and their well documented consequences. This study was designed to show that, in PD declarative as well as procedural memory is severely impaired. Three tests designed to explore this aspect of mnestic functioning were proposed to a group of 16 parkinsonian patients whose motoricity was controlled: inverted reading, braille reading, sound form association. The results obtained, compared with those of young and aged controls, show that PD is associated with marked deficits in both declarative and procedural memory. Declarative memory impairment was similar to that observed in the control population (healthy elderly subjects, age-matched with the PD patients) but more marked in PD subjects. The procedural memory deficit was linked with age and pathology. Procedural memory involves a variety of processing modules dedicated to the type of information (visual, auditive, tactile codes). The deficits observed were more like a loss of automatism than procedural impairment stricto sensu (''knowing how''). It would be worth pursuing research by studying akinesia and motor disorders from the angle of automatic memory impairment.
Dietary Changes, Compulsions and Sexual Behavior in Frontotemporal Degeneration
Authors: Miller Bruce L. , Darby Amy L. , Swartz J. Randolph , Yener Gorsev G. , Mena Ismael
Published: August 2007

The occurrence of weight gain, sweet and carbohydrate craving, hyposexuality, and compulsions in frontal lobe dementia (FLD) compared to Alzheimer’s disease (AD) was evaluated. FLD is a progressive dementia with a high rate of misdiagnosis and therefore better diagnostic criteria for FLD are needed. Fourteen patients meeting research criteria for AD were compared to 14 with suspected FLD. All had cerebral perfusion measured with xenon-133 and imaged with HMPAO using brain-dedicated SPECT. The FLD group showed frontotemporal and AD posterior temporoparietal hypoperfusion. The primary caregivers were queried regarding weight gain, sweet/carbohydrate preference, sexual drive, and compulsions. Differences were compared with Fisher''s exact test. The following was found in FLD versus AD: Weight gain in FLD patients amounted to 64% (AD 7%), carbohydrate craving was 79% (vs. 0%) and compulsive behavior 64% (vs. 14%). The differences for these symptoms were statistically significant, whereas for the symptoms increased sexual drive (8 vs. 8%) and reduced sexual drive (54 vs. 23%) no significant difference could be found. In FLD the first symptoms were often dietary changes or hyposexuality. Compulsions were more bizarre and severely disabling in FLD than in AD. Dietary changes, hyposexuality, and disabling compulsions are prominent early symptoms in FLD but not AD. The cause of these symptoms may be due to both frontal and subcortical serotonin loss and dysfunction of the anterior temporal lobes.
Atrophy of Hippocampal Formation Subdivisions Correlates with Stage and Duration of Alzheimer Disease
Authors: Bobinski M. , Wegiel J. , Wisniewski H.M. , Tarnawski M. , Mlodzik B. , Reisberg B. , de Leon M.J. , Miller D.C.
Published: August 2007

The hippocampal formations of 13 subjects with severe Alzheimer disease [AD; Global Deterioration Scale (GDS) stage 7] and of 5 age-matched subjects without symptoms of dementia were reconstructed from serial sections. Functional assessment staging (FAST) was used at the time of demise to assess 9 patients at stages 7a–c (incipient averbal and nonambulatory) and 4 patients at stages 7e–f (immobile). The duration of the disease from FAST stage 5 until demise ranged from 2 to 8 years in the first of these subgroups, and from 10 to 13 years in the second. The volumes of the entire hippocampal formation and of the cornu ammonis, its sectors and layers, the dentate gyrus, the subicular complex, and the entorhinal cortex were calculated. Hippocampal formation volume decreased by 36% in the incipient averbal and nonambulatory patients and by 60% in the severely functionally impaired immobile patients, in comparison with controls. In the final substages of AD, immobile patients exhibited significant atrophy, in comparison with controls, in the cornu ammonis and all of its sectors and layers except CA4, the subicular complex and all of its parts, and the entorhinal cortex (p < 0.05). Within the AD patient group, significant correlations were noted between both the magnitude of functional severity and the duration of AD and the volumes of most hippocampal formation subdivisions studied. For the cornu ammonis, subicular complex, and entorhinal cortex, volumetric loss correlations with FAST stage 7 ordinally enumerated substages were r = –0.71, –0.79, and –0.62, respectively. Calculations projected a decrease of 60% in the volume of the hippocampal formation over the duration of clinically manifest AD (from GDS and FAST stage 3 until demise). The projected decreases in the volumes of the cornu ammonis, subicular complex, and entorhinal cortex over the duration of AD were 64,70, and 51 %, respectively. We conclude that continuing changes occur in the hippocampal formation and most of its structural components throughout the clinical course of AD. These changes in the volume of the hippocampal subdivisions correlate with the stage and the duration of AD but not with age at onset of the disease.
Synaptophysin Immunoreactivity Is Stable 36 h Postmortem
Authors: Liu Xiaoying , Brun Arne
Published: August 2007

The effects of postmortem time, age and tissue storage time on synaptic density were investigated in the prefrontal cortex of human brains. Thirty normal cases and 10 patients with a variety of neurologic diseases were studied, using quantitative immunohistochemistry with a monoclonal antibody to synaptophysin. Synaptophysin immunoreactivity was stable during the first 36 h after death, showing no significant change at 1, 8, 12, 24 and 36 h postmortem in normals. However, at 48 and 72 h postmortem, synaptophysin immunoreactivity decreased significantly. A similar pattern of postmortem changes was found in the disease group. In 14 normal cases with a wide range of ages, a significant reduction in synaptic density with age was observed while the time of tissue storage as paraffin-embedded blocks had no significant effect on the synaptophysin immunoreactivity. These results support the validity of using synaptophysin immunohistochemistry as a measure of synaptic density in human brain autopsied within 36 h of death and stored as paraffin-embedded blocks for a long time.
Temporal Quantification of Alzheimer's Disease Severity: 'Time Index' Model
Authors: Ashford J. Wesson , Shan Minghua , Butler Steve , Rajasekar Arcot , Schmitt Frederick A.
Published: August 2007

A fundamental issue in the clinical and neuropathological assessment of Alzheimer''s disease patients is quantification of dementia severity progression. Several methods have been advanced for the purpose of staging dementia with various sensitivities at different phases of the disease, but no mathematical function has been developed to link these measures to a physical continuum. Using a dynamic method for quantifying illness severity, change in severity over time was referenced to a cumulative temporal index, a physical dimension. Data from 33 patients with probable Alzheimer''s disease with at least 2 successive assessments on three 50-point scales measuring cognitive, behavioral, and daily living skills were used to determine rate of change. ''Fuzzy-logic'' smoothing of the data, integration over time, and least-squares regression were used to derive a cubic polynomial function to calculate a severity measure in which ''days of illness'' was estimated from the severity score. This method can be used to improve the comparability of performance across various mental status tests, and to link measures of very early phases of preclinical dementia and late profound dementia phases. This method also provides a description of an ''average'' time course for any population from which the index is derived.
Changes in a CSF Antigen Associated with Dementia
Authors: Carretero M. Teresa , Harrington Charles R. , Wischik Claude M.
Published: August 2007

An 85-kDa antigen was detected in cerebrospinal fluid (CSF) using a monoclonal antibody, 11.57, raised against a fraction of paired helical filaments extracted from Alzheimer’s disease (AD) brain tissues. The antigen is a thermostable protein that is unrelated either to tau or amyloid β-protein precursor. Its level was measured in lumbar and post-mortem CSF samples and found to be decreased significantly in patients with dementia as compared with non-demented controls. There was no difference in its level between patients with AD and those with non-Alzheimer type dementia. In AD, however, there was a significant relationship between disease progression and the amount of the 85-kDa antigen.
A Case of Alzheimer’s Disease with Extensive Focal White Matter Changes
Authors: Zahner B. , Lang C.J.G. , Engelhardt A. , Thierauf P. , Neundörfer B.
Published: August 2007

The case of a patient is reported who suffered from disturbed concentration and memory and constructive apraxia. She had only mild neuropsychological deficits at the first examination. T2-weighted MRI presented extensive focal white matter changes. A brain biopsy showed changes typical for Alzheimer''s disease (AD). The extent of the white matter lesions was surprising compared to the mild clinical signs she had. This case confirms that AD may result in prominent white matter disease caused by incomplete infarction or demyelination.
Heat Shock Protein 70 mRNA Levels in Mononuclear Blood Cells from Patients with Dementia of the Alzheimer Type
Authors: Wakutani Yosuke , Urakami Katsuya , Shimomura Tokio , Takahashi Kazuro
Published: August 2007

The heat shock protein 70 (HSP70) gene is located in chromosome 14, it is now considered as a molecular ''chaperone'' and a cell-protective agent. It may be closely related to the pathogenesis of dementia of the Alzheimer type (DAT). To examine the relationship between HSP70 and DAT, HSP70 mRNA expression levels in mononuclear blood cells (MBCs) from patients with DAT were measured by Northern blotting. We found no significant correlation between HSP70 mRNA levels and aging. We found that HSP70 mRNA levels in MBCs from patients with DAT were significantly lower than those from patients with vascular dementia and nondemented controls. These findings suggest that the lower levels of constitutive HSP70 mRNA in DAT play an important role in developing DAT and that the measurement of HSP70 mRNA may be useful for the diagnosis of DAT.
Cognitive Performance after Small Strokes Correlates with Ischemia, Not Atrophy of the Brain
Authors: Stirling Meyer John , Obara Katsuyuki , Muramatsu Kazuhiro , Mortel Karl F. , Shirai Toshitaka
Published: August 2007

Computerized tomographic measures of recurrent cerebral infarctions, atrophy and local perfusion were all prospectively correlated with cognitive testing during treatment of risk factors plus antiplatelet therapy among vascular dementia patients. Neurological and cognitive status were quantified among 22 demented patients with small strokes and compared with 22 age-matched normal volunteers. In vascular dementia, risk factor control plus antiplatelet therapy reduced cerebral infarctions, increased perfusion, and stabilized or improved cognitive test performance, despite age-related, progressive cerebral atrophy.
Number of Platelet Dense Granules Varies with Age, Schizophrenia and Dementia
Authors: Kessler Abraham , Shinitzky Meir , Kessler Bezahl
Published: August 2007

In the present study we observed that the number of dense granules per platelet increases with age, attaining a maximum level above the age of about 40 years. Platelets of newborns apparently contain only a small number of dense granules per platelet. The numbers of platelet dense granules and platelet cell size in schizophrenic patients increase compared to age-matched healthy controls. In contrast, in Alzheimer-type dementia the number of platelet dense granules tends to decrease compared to healthy persons.
Alzheimers Disease: Distribution of Changes in Intraneuronal Lipopigment in the Frontal Cortex
Authors: Dowson Jonathan H. , Mountjoy Christopher Q. , Cairns Mary R. , Wilton-Cox Helen
Published: August 2007

Brains from 22 patients with Alzheimer''s disease (AD) and 20 non-diseased subjects were examined. Intraneuronal lipopigment in 2,440 nucleolated neurons throughout the depth of cortex was identifled by fluorescence microscopy. In the AD brains, the mean total area per neuron of the outlines of lipopigment was significantly increased in the region adjacent to the brain surface (sixths 1-3), and analysis of variance showed a significant interaction between depth of cortex (in sixths) and AD for this lipopigment variable (p = 0.012). After relating this lipopigment variable to the size of neuronal bodies, the results indicate that this change occurs in pyramidal neurons, although other neuronal types may also be affected. At least one of three AD-related changes in lipopigment was found in each sixth of the depth of cortex.
Electroencephalographic Correlates of Periventricular White Matter Lesions in Probable Alzheimer’ Disease
Authors: Lopez Oscar L. , Brenner Richard P. , Becker James T. , Jungreis Charles A. , Rezek Donald , DeKosky Steven T.
Published: August 2007

We evaluated the relationship between periventricular white matter lesions (PWMLs) and EEG abnormalities in probable Alzheimer''s disease (AD). We visually analyzed the EEG of 27 probable AD patients with mild to moderate degree of cognitive impairment participating in a longitudinal study of dementia. Patients had both CT and MRI scans performed at baseline examination, which also included an EEG. PWMLs were rated in CT and MRI films using a semiquantitative method. The EEGs were classified according to the Mayo Clinic Classification System. Abnormal EEGs correlated with PWMLs rating scores were detected on CT, but not on MRI. These data suggest that the presence of PWMLs contribute to the abnormal EEGs observed in AD patients, and that white matter abnormalities in CT correlate better with both the clinical findings and EEG than does the more sensitive but less specific MRI.
Aluminosilicate-lnduced Free Radical Generation by Murine Brain Glial Cells in vitro: Potential Significance in the Aetiopathogenesis of Alzheimer's Dementia
Authors: Evans Peter H. , Peterhans Ernst , Bürge Thomas , Klinowski Jacek
Published: August 2007

While previous studies have identified aluminosilicate deposits within the senile plaque cores from subjects with Alzheimer''s dementia, their possible role in the aetiopathogenesis of the disease remains unknown. In the present in vitro chemiluminescent study, we show that cultured murine glial cells exhibit the capacity to generate free radical and related oxygen-derived metabolites when exposed to various natural and synthetic model aluminosilicate particulate samples of differing particle size, morphology and composition. These results, if applicable to the proposed analogous in vivo situation in humans, suggest that further research into the biochemical and cellular mechanisms influencing the production and modulation of tissue-injurious free radical oxygen-derived metabolites within the brain, could have significant implications in the pathogenesis, prevention and treatment of Alzheimer''s disease.
Effects of L-α-Glycerylphosphorylcholine on Drug-Induced Behavioral Alterations in Rats
Authors: Drago Filippo , D'Agata Velia , Guidi Guido
Published: August 2007

Animals with learning and memory alterations induced by the intracerebroventricular administration of 6-hydroxydopamine or intraperitoneal injections of diazepam or buspirone were treated with L-α-glycerylphosphorylcholine (α-GPC) at the dose of 100 mg/kg/day for 20 days. The cognitive deficit, studied with the test of passive avoidance behavior, was recovered in all experimental groups. Motor activity tested with an open field was also increased by α-GPC. These results suggest that the mechanism of action of α-GPC involves, beside the cholinergic system, also other neurotransmitters in the brain.
Correlation between 99mTc - HMPAO Brain Uptake and Severity of Dementia in Alzheimer's Disease: Assessment Using an Automatized Technique
Authors: Robert Ph. , Migneco O. , Darcourt J. , Ricq O. , V.Aubin V. , Bonhomme P. , Pringuey D. , Lapulus F. , Darcourt G.
Published: August 2007

The aim of this study was to evaluate the correlations between the degree of dementia and the regional brain distribution of 99mTc-HMPAO in Alzheimer patients. Mini Mental Status Examination (MMSE) was used for deterioration evaluation. Regional cortical HMPAO uptake was analyzed by single photon emission tomography and an automatic technique for determination of lobe boundaries. Five regions were analyzed for each hemisphere: frontal, parietal, temporal, occipital and temporoparietal (TP). 39 patients satisfying the NINCDS-ADRDA criteria for probable Alzheimer''s disease (AD) and 10 controls of comparable age were included. There is a significant correlation between MMSE and the HMPAO uptake of the right temporal region of interest (p < 0.001) and right TP (p < 0,01) and left TP (p < 0.05). However, the regression curve is nonlinear, showing a strong correlation for severe cases (MMSE < 15) and a weak correlation for moderate cases. Within the subgroup of severe AD (n = 21; mean MMSE = 8.5) linear correlations are observed for parietal and occipital (p < 0.05), temporal and TP (p < 0.01) ROIs, but only on the right side. There is no significant correlation among the moderate AD subgroup (n = 18; mean MMSE = 20). We conclude that the HMPAO uptake of temporal and TP regions of the right hemisphere is correlated to the degree of dementia among severely demented patients.
Severity of Symptoms and Rate of Progression in Alzheimer's Disease: A Comparison of Cases with Early and Late Onset
Authors: Haupt M. , Kurz A. , Pollmann S.
Published: August 2007

Since first description of Alzheimer''s disease rapid symptom progression and relatively severe cognitive symptoms have been frequently associated with early age of onset, while slow symptom progression and relatively mild cognitive symptoms were often related to late age of onset. In a longitudinal study of 90 patients with mild to moderate Alzheimer''s disease, we investigated these hypotheses. We found that neither severity of cognitive symptoms nor symptom progression in Alzheimer''s disease were associated with age of onset. In addition, a comparison of extreme groups (group 1: < 60 years of age; group 2: > 75 years of age), taken from the study sample, showed similar results with respect to the independent variables. These results suggest that the interindividual variability of cognitive impairment as well as the large variation of symptom progression in Alzheimer''s disease cannot be explained by age of onset.
Transcranial Doppler Sonography in the Early Phase of Alzheimer's Disease
Authors: Bressi S. , Volontè MA. , Alberoni M. , Canal N. , Franceschi M.
Published: August 2007

Transcranial Doppler sonography examination of 23 patients with Alzheimer''s disease (AD) showed significantly slower blood flow velocities, bilaterally, in the middle cerebral arteries (MCAs) than in 10 healthy controls. The asymmetries of velocities in MCA were positively correlated with asymmetries of cognitive impairment, but not with global severity or duration of disease. Patients with prevalent left hemispheric neuropsychological dysfunction showed significantly slower blood flow in the left MCA, while the opposite pattern was observed in patients with prevalent right hemisphere dysfunction. The possibility that these findings are an expression of the reduction of cerebral blood flow and metabolism shown in AD by emission tomography studies is discussed.