bluuebunny/crossref_metadata_2025 huggingface dataset:
Apolipoprotein E and Alzheimer's Disease: Strength of Association Is Related to Age at Onset
Authors: Murman D.L. , Foster N.L. , Kilgore S.P. , McDonagh C.A. , Fink J.K.
Published: August 2007

Apolipoprotein E (apoE) Ε4 allele frequency among Alzheimer''s disease (AD) patients is increased compared to control subjects and is influenced by the presence of other genetic factors and age at symptom onset. We examined the relationship between age at AD symptom onset and apoE by comparing the apoE Ε4 allele frequency of normal, elderly control subjects (n = 107) to that in AD patients (n = 123), divided into four age-at-onset periods. Additionally, the distribution of symptom onset ages of AD patients with and without apoE Ε4 alleles was determined. We observed increased apoE Ε4 allele frequencies between the AD onset ages of 55 and 75 years, but not at the extremes of onset ages (i.e. onset between 45 and 54 years of age and after age 75). Our data suggests that having an apoE Ε4 allele increases the likelihood that AD patients will develop symptoms in the middle range of onset ages. At the extremes of AD onset ages, non-apoE factors, including other genetic factors and age, are more important determinants of risk of developing AD.
Serum Amyloid P Component Level in Alzheimer's Disease
Authors: Nishiyama Etsuko , Iwamoto Norihiko , Kimura Michihiro , Arai Heii
Published: August 2007

Serum amyloid P component (AP) is a normal plasma constituent that is observed in senile plaques and neurofibrillary tangles in brains of Alzheimer''s disease (AD) patients. In this study we have evaluated the AP levels in sera of 16 patients with AD and in 16 control subjects by enzyme-linked immunosorbent assay. The AP level was 22.4 ± (SD) 7.0 µg/ml in the AD group and 34.4 ± (SD) 6.6 µg/ml in the control group. The AP level in the AD group was significantly lower than that of the control group (p < 0.01). In the control group, there was no correlation between AP levels and age. Our results suggest that the production of AP by the liver (hepatocytes), thought to be the only source, may be suppressed in AD patients and that the deposition of AP in senile plaques and neurofibrillary tangles is not due to its overproduction.
Apolipoprotein E in Cerebrospinal Fluid from Patients with Alzheimer's Disease and Other Forms of Dementia Is Reduced but without Any Correlation to the apoE4 Isoform
Authors: Landén Mikael , Hesse Camilla , Fredman Pam , Regland Björn , Wallin Anders , Blennow Kaj
Published: August 2007

Apolipoprotein E (apoE) has been suggested to play a role in regenerative processes in the brain after trauma, and also in the pathogenesis of Alzheimer''s disease (AD). We examined cerebrospinal fluid (CSF) apoE in a material consisting of 23 patients with early-onset AD (EAD), 31 with late-onset AD (LAD), 16 with frontal-lobe dementia (FLD), 25 with vascular dementia (VAD) and 25 controls. CSF-apoE was decreased in all of EAD (1.8 ± 1.1 mg/l; p < 0.0005), LAD(2.5 ± 0.9mg/l; p < 0.0005),VAD (2.3 ± 1.4mg/l; p < 0.0005) and FLD (3.0 ± 1.3 mg/l; p < 0.05) compared to the control group (5.7 ± 4.0 mg/l). Since apoE4 has been found to bind to β/A4-amyloid, and AD patients homozygous for apoE4 to have higher number of senile plaques than apoE3 homozygotes, we also examined the relation between CSF-apoE and apoE alleles. However, CSF-apoE did not significantly differ between patients with different apoE isoforms. Our findings support that apoE is involved in the pathogenesis of dementia disorders, both degenerative and vascular, but the CSF-apoE level is not influenced by the apoE isoforms. CSF-apoE may be used as an unspecific marker for neurodegenerative disorders, but not in purpose of differential diagnostics between different dementia disorders.
Regional Brain Atrophy in Idiopathic Parkinson's Disease and Diffuse Lewy Body Disease
Authors: Double K.L. , Halliday G.M. , McRitchie D.A. , Reid W.G.J. , Hely M.A. , Morris J.G.L.
Published: August 2007

This study measured brain atrophy in patients with idiopathic Parkinson''s disease and diffuse Lewy body disease, all of whom had equivalent loss of midbrain dopaminergic neurons and absence of Alzheimer''s disease. Characteristic patterns of volume loss were found throughout the brain, depending on the age of onset and clinical signs. An equivalent loss of medial temporal lobe structures occurred in all parkinsonian patients. This atrophy was similar in magnitude to that seen in Alzheimer''s disease and is likely to be the anatomical substrate for the memory deficits found in each of these patient groups. Frontal lobe atrophy was a feature of both late-onset Parkinson''s disease (mild atrophy) and diffuse Lewy body disease (significant atrophy) groups, with all cases analyzed having dementia. Atrophy of frontal lobes correlated with the duration of motor symptoms in these patients and may suggest an association between dopaminergic deafferentation, frontal atrophy and dementia.
Quantitative Electroencephalography Power and Coherence in Alzheimer's Disease and Mild Cognitive Impairment
Authors: Jelic Vesna , Shigeta Masahiro , Julin Per , Almkvist Ove , Winblad Bengt , Wahlund Lars-Olof
Published: August 2007

In this study the best combination of quantitative electroencephalographic variables (qEEG) for the discrimination of groups with mild to moderate Alzheimer''s disease (AD), mild cognitive impairment and healthy subjects was defined and related to neuropsychological performance. The study population included 18 patients with mild to moderate probable AD, 19 subjects with objective memory disturbances, 17 subjects with subjective memory complaints who did not have clinical evidence of memory disturbance, and 16 healthy controls. AD patients had significantly increased theta and decreased alpha relative power, mean frequency, and temporoparietal coherence. There was no significant difference in the mean frequency in the left temporal region between AD patients and subjects with objective memory disturbances. Temporoparietal coherence appeared as a discriminant variable together with alpha and theta relative power only between AD patients and controls, giving 77.8% sensitivity and 100% specificity. Significant correlations between regional changes in qEEG variables and cognitive functions were found.
An Algorithmic Approach to the Differential Diagnosis of Dementia
Authors: Graham Janice. E. , Mitnitski Arnold B. , Mogilner Alexander J. , Gauvreau Denis , Rockwood Kenneth
Published: August 2007

The careful definition of cases is fundamental to diagnosis and to any study of cognitive, behavioural and functional problems in dementia. This paper presents an algorithmic approach which mimics a crucial component of diagnostic decision-making; symptoms and signs do not occur independently, but are conditioned on each other. First, we examine whether the conditioned items can be assembled to yield a differential diagnosis of dementia which corresponds to clinical diagnoses, and second, we explore whether subjects whose algorithmic profiles do not fit the clinical diagnoses form new discernable patterns. Such a technique offers two advantages: it allows for the development of validation protocols which are crucial to epidemiological studies, and it allows for the analysis of new patterns of signs and symptoms for emerging criteria of dementia subtypes. This approach has the potential to refine and enhance criteria for the differential diagnosis of dementia and to have an impact on case identification and assessment, particularly in large epidemiologic studies.
Neuronal Ultrastructural Abnormalities in a Patient with Frontotemporal Dementia and Motor Neuron Disease
Authors: Chang Linda , Cornford Marcia , Miller Bruce L. , Itabashi Hideo , Mena Ismael
Published: August 2007

Motor neuron disease (MND) can be associated with frontotemporal dementia (FTD) and circumscribed lobar atrophy of frontal and temporal lobes. Neuropathological correlations were sought in postmortem studies from a woman with these associated conditions. Cerebral blood flow imaging and autopsy showed cortical abnormalities in the frontal and temporal lobes, but typical argyrophilic Pick''s bodies were absent and ubiquitin-positive neuronal cytoplasmic inclusions were rare. However, hematoxylin and eosin staining revealed eosinophilic, granular, central cytoplasmic ‘clearing’ in most neurons of the substantia nigra and in cervical anterior horn cells. Electron microscopy showed that these neurons contained a central cytoplasmic zone cleared of neuromelanin and normal cytoplasmic organelles containing small mitochondria with matrix inclusions and randomly oriented filamentous material. A mitochondrial dysfunction or defective transport of mitochondria into axonal processes needs to be studied as a potential cause for the coassociation of MND and FTD.
Correlations between Cognitive Impairment, Middle Cerebral Artery Flow Velocity and Cortical Glucose Metabolism in the Early Phase of Alzheimer’s Disease
Authors: Franceschi M. , Alberoni M. , Bressi S. , Canal N. , Comi G. , Fazio F. , Grassi F. , Perani D. , Volonté M.A.
Published: August 2007

In a previous transcranial Doppler (TCD) study, we demonstrated a decrease in blood flow velocity in the proximal tract of the middle cerebral artery (MCA) in patients with Alzheimer’s disease (AD). In these patients there was also an asymmetry in blood flow velocity which positively correlated with the cognitive asymmetry often seen in the early phase of AD. In this study we found a correlation between the absolute values and asymmetry indexes of MCA blood flow velocity with adjusted metabolic values and asymmetry indexes of the relative cortical frontotemporoparietal (FTP) areas, evaluated by FDG-PET, and with neuropsychological asymmetry indexes. Patients with prevalent visuospatial deficits (right hemisphere dysfunction) showed significant decreases in right MCA blood flow velocity and right FTP cortical glucose hypometabolism, whereas in patients with prevalent language deficits (left hemisphere dysfunction), these signs were observed on the other side. In AD patients, the decrease of blood flow velocity in MCA might be due to reduced metabolic demands in the temporoparietal cortical areas primarily affected by AD.
Bone Aluminium Content in Alzheimers Disease
Authors: O’Mahony D. , Denton J. , Templar J. , O’Hara M. , Day J.P. , Murphy S. , Walsh J.B. , Coakley D.
Published: August 2007

The possible association between aluminium and Alzheimer’s disease is still contentious. If aluminium neurotoxicity is implicated in the pathophysiology of Alzheimer''s disease, it may result either from excessive aluminium exposure or increased brain aluminium uptake. In a pilot study to test the former hypothesis, trabecular bone aluminium content, which reflects long-term aluminium exposure, was evaluated in 7 patients with a clinical diagnosis of senile dementia of the Alzheimer type (SDAT; mean age 80.8 ± 3.35 years) and 19 non-demented age-matched controls (mean age 79.6 ± 6.09 years). Trabecular bone was obtained from post-traumatic femoral neck fracture specimens taken from patients during femoral head prosthesis surgery. Bone aluminium content was expressed quantitatively by atomic absorption spectrometry and qualitatively by the acid solochrome azurine histological staining technique. Quantitative analysis showed a lower aluminium content in the SDAT (11.9 ± 4.04 µg/g dry bone) versus the non-demented group (18.2 ± 7.37 µg/g), which was significant at the 95% but not at the 99% confidence limit. Aluminium deposition from qualitative histological analysis was not detectable in either group. These results do not support a hypothesis of excessive aluminium absorption and tissue accumulation in Alzheimer''s disease.
Cerebrovascular Reactivity to Acetazolamide in (Senile) Dementia of Alzheimer’s Type: Relationship to Disease Severity
Authors: Stoppe Gabriela , Schütze Rainer , Kögler Andreas , Staedt Jürgen , Munz Dieter L. , Emrich Dieter , Rüther Eckart
Published: August 2007

Neuropathological reports about denervation and amyloid angiopathy in dementia of Alzheimer''s type (DAT) as well as signs of selective incomplete white matter infarctions point to a vascular involvement within the degenerative process. In order to investigate potential alterations of cerebrovascular function we performed cerebral blood flow measurements before and after intravenous injection of 1 g acetazolamide using technetium-99m hexamethylpropyleneamine oxime and single photon emission tomography in 12 patients (6 female, 6 male; mean age 70.8 ± 9.6 years) with probable (senile) dementia of Alzheimer''s type (SDAT) and 9 controls (7 female, 2 male; mean age 71.2 ± 8.6 years). SDAT patients revealed significantly reduced cerebrovascular reactivity with lower values with increasing cognitive impairment. We discuss possible underlying mechanisms.
Twelve-Month Follow-Up Study of Regional Cerebral Blood Flow in Parkinson's Disease
Authors: Tachibana Hisao , Tomino Yoshio , Kawabata Keita , Sugita Minoru , Fukuchi Minoru
Published: August 2007

Measurement of regional cerebral blood flow (rCBF) in 30 patients with Parkinson''s disease using single-photon emission computed tomography and 123I-IMP demonstrated that hypoperfusion was relatively severer in the parietal cortex than other cortices before and after a 1-year follow-up period. The decline in the scores of the Mini-Mental State Examination was significantly correlated with the decrease in rCBF in the parietal cortex during the follow-up period. Our flndings suggest that the parietal cortex is involved in the cognitive impairment in patients with Parkinson''s disease.
Predictors of Mortality and Institutionalization in Alzheimer Disease Patients 1 Year after Discharge from an Alzheimer Dementia Unit
Authors: Bianchetti Angelo , Scuratti Alberto , Zanetti Orazio , Binetti Giuliano , Frisoni Giovanni B. , Magni Eugenio , Trabucchi Marco
Published: August 2007

Several factors have been reported to predict death and institutionalization in demented patients, even if the results of the studies are often conflicting. We conducted a study on a group of 86 consecutive noninstitutionalized probable Alzheimer disease (AD) patients, to evaluate clinical and social factors predicting mortality and institutionalization 1 year after discharge from the Alzheimer Dementia Unit at ''Sacro Cuore Fatebenefratelli’ Hospital, Brescia, Italy. The 1-year mortality rate was 13.9% and the 1-year rate of admission to a nursing home was 34%. Our data indicate that the number of lost functions on the Activity of Daily Living scale is the most important predictor of short-term mortality, independently of the degree of cognitive impairment, the duration of the dementia, the age of the patients and the number of chronic diseases. Our data also demonstrate that, in a short period of observation, behavioral disturbances (and in particular insomnia) and availability of social Services play a major role in the decision to institutionalize AD patients.
Neuropathological Diagnoses in Elderly Patients in Oslo: Alzheimers Disease, Lewy Body Disease, Vascular Lesions
Authors: Ince Paul G. , McArthur Fiona K. , Bjertness Espen , Torvik Ansgar , Candy John M. , Edwardson James A.
Published: August 2007

Neuropathological changes in elderly residents of Oslo, Norway, were characterised with respect to the cerebral substrates of dementia. Ninety-two brains were examined, representing 41% of all deaths occurring in 10 nursing homes during a 9-month period. The autopsy cohort showed a similar mean age (85 years) and sex ratio (73% female) and proportion of demented patients (75%) compared to all the patients resident in these homes who died during the same period. Clinical data was compiled retrospectively. Diagnosis was made using the CERAD protocol, and criteria for the diagnosis of Lewy body dementia. Lewy body formation was present in 20% and cerebral infarction in 21% of patients. In the demented group (69 patients) 90% fulfilled CERAD criteria for definite or probable Alzheimer’s disease. Eight demented cases had absent neocortical neurofibrillary tangles and 6 other cases showed Lewy body dementia (9% of demented patients). A further 8 of these demented cases had brain stem Lewy bodies with only minimal cortical involvement. Thirteen cases (19% of the sample) had cerebral infarcts but these were considered to be clinically significant in only 4 (6%). In the non-demented patients (23) 4 patients had brain stem Lewy bodies and 6 had cerebral infarcts. Despite inclusion criteria biased towards the collection of Alzheimer''s disease and normal patients, both Lewy body dementia (7%) and cerebral infarcts contributing to dementia (6%) were frequent
Transient Enhancement of Cholinergic Neurochemical Markers Induced by NGF in Aged F344 Rats
Authors: Santucci Anthony C. , Kanof Philip D. , Haroutunian Vahram
Published: August 2007

Two experiments were conducted to assess the durability of nerve growth factor (NGF) effects on cholinergic neurochemical markers. Artificial CSF or NGF was infused via osmotic pumps for 2 weeks into the lateral ventricles of young adult (3- to 6-month-old) and aged (22- to 26-month-old) Fischer 344 rats. Assessment of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) within the cortex, striatum, and hippocampus was conducted either approximately 3 (experiment 1) or 12 (experiment 2) weeks after termination of treatment. A variety of age-related deficiencies were found in the two experiments with decreased marker levels within the dorsal hippocampus and striatum being most consistent. NGF increased cholinergic marker enzyme activity in experiment 1 only. Specifically, NGF (a) attenuated age-related CAT and AChE deficits within the dorsal hippocampus and striatum, (b) enhanced CAT activity within the frontal cortex and ventral hippocampus in aged animals, and (c) increased CAT activity within the dorsal hippocampus in young subjects. It is concluded that NGF may be beneficial in enhancing cholinergic neurochemical parameters, especially in aged animals, but such effects are most likely transient.
A Decrease in Neural Sialyltransferase Activity in Alzheimer’s Disease
Authors: Maguire Teresa M. , Breen Kieran C.
Published: August 2007

The activities of both a particulate and soluble form of the sialyltransferase enzyme have been examined in post-mortem brain samples from Alzheimer''s disease patients and age-matched controls. There was a considerable decrease in the activity of both the soluble and membrane-bound forms of the enzyme in the frontal and temporal cortical lobes, although no change was observed in the hippocampus. There was, however, no change in activity of the Golgi marker enzyme thiamine pyrophosphatase. Therefore, it is suggested that the decrease in sialyltransferase enzyme activity may be a specific biochemical event associated with the AD-like neurodegeneration.
Familial Alzheimer’s Disease and Cortical Lewy Bodies: Is There a Genetic Susceptibility Factor?
Authors: Lippa Carol F. , Smith Thomas W. , Nee Linda , Robitaille Yves , Crain Barbara , Dickson Dennis , Pulaski-Salo D. , Pollen Daniel A.
Published: August 2007

The reason for the occurrence of Lewy body disease (LBD) in Alzheimer''s disease (AD) patients in unknown. If brains from etiologically different AD groups differ in their tendency to develop cortical Lewy bodies, the concurrence of LBD in AD patients may be a manifestation of the AD process in specific AD subsets. To address this issue, we counted cortical Lewy bodies in AD patients with genetic abnormalities on chromosome 14 (n = 19), and chromosome 21 (n = 3), sporadic AD (n = 27), Down''s Syndrome (n = 1) and control (n = 26) patients. Cortical Lewy bodies were occasionally present in AD patients with long-duration disease in most of the above AD subgroups, but were not present in any of our age-matched control cases. We suggest that cortical Lewy body formation may be an intrinsic part of the late pathologic changes of AD regardless of etiology and that it is not specific to any of the AD subtypes studied.
Leukocyte Hexokinase Activity in Aging and Alzheimer Disease
Authors: Antuono Piero G. , Ravanelli-Meyer J. , Nicholson K. , Bloom Alan S.
Published: August 2007

We determined the effects of clinical variables on hexokinase (HK) activity in leukocytes from Alzheimer''s disease (AD) patients and controls. Age accounted for 51% of the variance in HK activity in the young and 23% in the old. Duration of illness in both familial and sporadic AD accounted for HK levels by 32 and 38%, respectively. Hexokinase activity increases with age and does not discriminate between familial and sporadic AD.
Striatonigral Degeneration Combined with Olivopontocerebellar Atrophy with Subcortical Dementia and Hallucinatory State
Authors: Fukutani Y. , Takeuchi N. , Kobayashi K. , Miyazu K. , Yamaguchi N. , Terada T. , Nakamura I. , Isaki K.
Published: August 2007

We present an autopsied case of striatonigral degeneration (SND) combined with olivopontocerebellar atrophy (OPCA) with subcortical dementia and hallucinatory state. A Japanese woman without a remarkable family history showed hand tremor at the age of 35 years, followed by bradykinesia, muscle rigidity, orthostatic hypotension, neurogenic bladder and pyramidal signs. No obvious cerebellar symptoms were found. Various antiparkinsonian drugs were administered, but were not markedly effective for the parkinsonism. She developed a mild dementia characterized by mild memory disturbance with preservation of orientation, slowing of thought processes, emotional Iability toward sadness, impaired ability to manipulate acquired knowledge and poor calculating, and by the absence of aphasia, apraxia and agnosia. The features in this patient were consistent with those seen in subcortical dementia. She also had auditory hallucinations. MRI revealed hypointense T2 signals in the putamina and substantia nigra. T1-weighted MRI demonstrated atrophy of both the pons and cerebellum in addition to atrophy of the putamina and substantia nigra. EEG showed slowing of background activity. She died of cardiac failure at the age of 47. Autopsy disclosed brain stem tegmental atrophy, SND, OPCA and many glial cytoplasmic inclusions in the central nervous system, but well-preseved cerebrum. We discuss the relationship between the psychiatric symptoms and pathologic findings of brain stem tegmentum.
Changes of the Relative Severity of Naming, Fluency and Recall Impairment in the Course of Dementia of the Alzheimer Type
Authors: Pollmann S. , Haupt M. , Kurz A.
Published: August 2007

In a longitudinal study of 90 patients with mild to moderate dementia of the Alzheimer type (DAT) we investigated the relative severity of impairment in a confrontation naming, a categorical word fluency and a word list recall task. Severity of impairment was assessed in comparison to a healthy age-matched control group. At baseline, confrontation naming and fluency deficits were about equally often the most severe deficit. The number of patients with most severe naming deficits increased from mild to moderate dementia and from baseline to 1-year follow-up. Word recall was the most severe deficit only in a minority of patients. An addition of lexical-semantic and visual-perceptive dysfunctions is discussed as a possible cause for the shift towards naming deficits in the course of the disease.
Effect of Seizures on Progression of Dementia of the Alzheimer Type
Authors: Volicer Ladislav , Smith Sally , Volicer Beverly J.
Published: August 2007

A survey of institutionalized patients with clinical diagnosis of probable dementia of the Alzheimer type (DAT) indicated that 21% of patients developed seizures after the onset of DAT. Of the total of 27 patients, 11 developed seizures at home and 16 after institutionalization. In 9 of the 11 patients (82%), who suffered the initial seizure at home, the patients'' condition suddenly worsened and required long-term care admission within 6 months of the seizure onset. Language function declined significantly more rapidly in 5 patients with seizures than in controls matched by age and duration of DAT.
Eye Movement Dysfunction in Dementia of the Alzheimer Type
Authors: Moser A. , Kömpf D. , Olschinka J.
Published: August 2007

Patients with dementia of the Alzheimer type (DAT) are described to have disturbances in basic visual, complex visual and oculomotor functions. In order to study and quantify dysfunction of eye movements under several paradigms, they were measured with infrared photoelectric techniques and analyzed by a digital Computer. The study included 12 normal subjects and 10 patients with mild to moderate DAT (DSM-III-R criteria). The authors'' results could demonstrate both an attentional deficit to externally triggered, unpredictable targets and an impaired systematic, voluntary, internally organized scanning of the environment due to motivational and perceptional deficits.
Intravascular Malignant Lymphomatosis: A Cause of Subacute Dementia
Authors: Treves T.A. , Gadoth N. , Blumen S. , Korczyn A.D.
Published: August 2007

Intravascular malignant lymphomatosis (IML) is a rare disease characterized by proliferation of neoplastic cells of lymphoid origin within small blood vessels. The median survival of IML patients is only 6 months. Any organ can be affected, with or without clinical expression. Although skin lesions are classic, they are relatively uncommon (28%). Neurological symptomatology (which evolves over a few weeks) is the most common clinical expression (83%). Dementia is the most common neurological symptom that occurs in about half of the patients with central nervous system pathology, and is associated with poorer prognosis. The diagnosis is confirmed by histology but, except for lung, biopsies are not sensitive and are helpful only when performed in the symptomatic organs; furthermore, when associated with anesthesia, they can be followed by dramatic worsening of the patient''s condition. Elevated LDH is a good indicator of IML in patients with subacute neurological symptomatology, especially if associated with signs suggestive of other organ involvement.
Chromogranin A in Cerebrospinal Fluid: A Biochemical Marker for Synaptic Degeneration in Alzheimer’s Disease?
Authors: Blennow K. , Davidsson P. , Wallin A. , Ekman R.
Published: August 2007

Biochemical markers for AD would be of great value both to improve the clinical diagnostic accuracy in scientific studies and to increase the knowledge of the pathogenesis of the disorder. One of the main features of AD is a degeneration of synapses. Therefore, we examined if chromogranin A (CrA), the major protein of large dense-core synaptic vesicles, in cerebrospinal fluid (CSF) may be of value as a biochemical marker for the synaptic function in AD. The mean concentration of CrA in CSF was about 7.5 times higher than its concentration in serum, and there was no significant correlation between CSF-CrA and the blood-brain barrier function (measured as the CSF/serum albumin ratio), nor between CSF-CrA and serum-CrA. These findings suggest that the major portion of CSF-CrA is locally produced within the CNS. There were no significant differences in CSF-CrA between the AD (n = 29), vascular dementia (n = 13), and age-matched control (n = 9) groups (99.9 ± 58.9 ng/ml, 108.0 ± 69.4 ng/ml, and 115.1 ± 44.4 ng/ml, respectively). However, when the AD group was subdivided into AD type I (n = 12) and AD type II (n = 17), a lower concentration of CSF-CrA was found in AD type I (72.8 ± 28.9 ng/ml) compared with controls (115.1 ± 44.4 ng/ml), p < 0.02, and compared with AD type II (119.1 ± 67.5 ng/ml), p < 0.05, while CSF-CrA did not significantly differ between AD type II and controls. These findings suggest that CSF-CrA has a potential as a biochemical marker for the synaptic degeneration in AD type I, and gives further support for the relevance of identifying the AD type I (pure AD) subgroup in scientific studies.
Evidence of Blood-Cerebrospinal Fluid-Barrier Impairment in a Subgroup of Patients with Dementia of the Alzheimer Type and Major Depression: A Possible Indicator for Immunoactivation
Authors: Hampel H. , Müller-Spahn F. , Berger C. , Haberl A. , Ackenheil M. , Hock C.
Published: August 2007

Serum and cerebrospinal fluid (CSF) from 44 patients with clinical probable Alzheimer''s disease (AD) (subdivided in two groups with 18 early onset, EO, and 26 late onset, LO, cases), 10 patients with vascular dementia (VD) and 24 patients with major depression (MD) were assayed for concentrations of albumin and IgG. The severity of dementia was assessed with the Mini Mental State Examination. The CSF/serum ratio for albumin and IgG as well as the IgG index were used to evaluate blood-CSF barrier function. Various patients showed signs of blood-CSF-barrier (BCB) dysfunction and only few displayed evidence of local IgG synthesis in the central nervous system (CNS) in the AD, VD and in the MD group (IgG index >0.7). The permeability of the blood-CSF barrier was not correlated to measures of dementia severity. Our data support the hypothesis of a BCB leakage in a subgroup of all investigated patients. Furthermore, we found a small number of patients with increased intrathecal IgG synthesis. Elevated CSF immunoglobulins combined with BCB impairment might be associated or caused by a general immune activation. Our data are in agreement with the assumption that an inflammatory process may play a role in a subgroup of patients with AD but also with MD and less likely in VD. In conclusion BCB impairment and elevated IgG Immunoglobulin levels are unspeciflc either for AD, VD or MD.
Cumulative Risk of Alzheimer-Like Dementia in Relatives of Autopsy-Confirmed Cases of Alzheimer’s Disease
Authors: Hocking Leslie B. , Breitner John C.S.
Published: August 2007

The cumulative risk of Alzheimer-like dementia (AD) was investigated in first-degree relatives (n = 176) of 35 probands with autopsy-confirmed clinical diagnoses of Alzheimer''s disease. Seventeen of the 176 first-degree relatives showed evidence of AD. Cumulative morbid risk for the first-degree relatives was estimated to be 28.8%. This result is broadly consistent with previously reported studies, and affirms the presence of substantial disease risk in close relatives of those with Alzheimer''s disease
Evaluation of the Hachinski Ischemic Scale in a Prospective Study
Authors: Nussbaum M. , Treves T.A. , Korczyn A.D.
Published: August 2007

The Hachinski ischemic scale (HIS) is the favored clinical tool used in the differentiation between degenerative dementia and multi-infarct dementia. Application of the HIS results in an additional subtype of dementia termed ''mixed'' dementia. More significantly, distribution of the scores obtained has a skewed rather than a bimodal pattern, which does not agree with the original framework of the test, namely to distinguish between the two different nosological entities. This prompted us to evaluate the scale, and a modification is proposed in which several non-discriminating items are excluded. Application of the modified HIS to a series of 98 demented patients consecutively admitted to a drug study, resulted in a bimodal distribution of the scores obtained and in a smaller size of the intermediate group, supporting the improved diagnostic reliability of this version.
Maternal Age and Alzheimer's Disease
Authors: Clarnette Roger , Molloy D. William , McIlroy William E. , Lever Judy , Rees Linda
Published: August 2007

The pathogenesis of Alzheimer''s disease (AD) is contributed to by genetic factors, but the mechanism is unknown. Because of the pathological similarities between AD and Down''s syndrome, it has been suggested that increased maternal age may influence the transmission of AD. Studies which have examined maternal age in AD subjects have shown inconsistent results. We performed a case-control study using data from 214 persons referred to a Memory Clinic. The parental age of 64 patients with probable AD was compared to that of 78 patients with possible AD, 72 with other diagnoses and spouses. Although there was a trend towards higher maternal age in those with probable AD, the differences were not significant. A review of the literature reveals difficulties with case-control methodology and variability in case definition and control collection. We conclude that determining whether maternal age is increased in subjects with AD may not be possible using case-control methodology.
Validation Study of the Italian Version of the Cambridge Mental Disorders of the Elderly Examination: Preliminary Findings
Authors: Neri M , Andermacher E. , Spanó A. , Salvioli G. , Cipolli C.
Published: August 2007

A validation study was planned to assess, by comparing the performance of a group of suspected demented (i.e. scoring less than 27 in the Mini Mental State Examination, MMSE) and a control group of normal aged subjects, (a) whether the Cambridge Mental Disorders of the Elderly Examination (CAMDEX) interview maintains in the Italian version the characteristics of sensitivity and specificity established in the English one and (b) whether the concurrent validity of the CAMDEX (with respect to psychometric tests such as MMSE, Geriatric Depression Scale and Extended Dementia Scale, is satisfactory. In this paper some preliminary findings (obtained on 31 of the 50 subjects of each group) are reported. Each subject was examined by the MMSE and other psychometric tests, and, in a separate session, the Italian version of the CAMDEX. This version or an abridged one had to be (re-)administered after 3 or 12 months to one or the other half of both groups. All the suspected demented subjects reached a Cambridge Cognitive Examination (CAMCOG) score under the cut-off point for dementia, while only 8 control subjects scored under this point, with a significant difference in the mean score of the two groups. Moreover, CAMCOG scores were highly correlated with those of the MMSE and, in suspected demented subjects, with those of the Gottfries-Brane-Steen scale. These findings suggest that the sensitivity of the CAMDEX is maintained in the Italian version, while the specificity seems to be less satisfactory. This conclusion needs further support by findings from larger samples and from follow-up studies.
Sporadic Olivopontocerebellar Atrophy with 'Subcortical Dementia' and Hallucinatory Paranoid State: Report of an Autopsy
Authors: Fukutani Y. , Katsukawa K. , Kobayashi K. , Nakamura I. , Miyazu K. , Yamaguchi N. , Watanabe K.
Published: August 2007

An autopsied case of sporadic olivopontocerebellar atrophy with ''subcortical dementia'' and hallucinatory paranoid state is reported. A Japanese woman without a remarkable family history showed cerebellar ataxia at the age of 61 years, followed by muscle rigidity, pyramidal signs, peripheral amyotrophy and ophthalmoplegia. She had paranoid delusion and visual and auditory hallucinations. She also developed a dementia characterized by mild memory disturbance with preservation of orientation, slowing of thought processes, affective changes including apathy and depression, impaired ability to manipulate acquired knowledge and the absence of aphasia, apraxia and agnosia. These features were consistent with those seen in subcortical dementia, first proposed by Albert. Autopsy revealed pontine tegmental atrophy in addition to a marked atrophy of the inferior olivary nucleus, pontine basis and cerebellum, in contrast to a relatively well-preserved cerebrum. The peculiar psychotic features including dementia found in the patient are discussed from a clinicopathological standpoint.
Visual Pattern Recognition Memory and Learning Deficits in Senile Dementias of Alzheimer and Lewy Body Types
Authors: Galloway Peter H. , Shagal Arjun , McKeitha, bJolles Ian G. , Cook Julia H. , Ferrier I. Nicol , Edwardson James A.
Published: August 2007

Senile dementia of Alzheimer''s type (SDAT) and the recently described senile dementia of Lewy body type (SDLT) are both characterized by marked cognitive deterioration. In this study we compare and contrast neuropsychological profiles in the two disorders. The tests described include some well-known standard psychometric tests as well as pattern recognition (PR) and conditional learning paired associate (CLPA) tasks taken from the computerised Cambridge Neuropsychological Test Automated Battery. Most of the standard tests were unable to distinguish between SDAT and SDLT. The SDLT patients were more severely impaired on the computerised CLPA task, and generally took longer to respond. It is suggested that the severe mnemonic deficiencies seen in SDLT result from relatively marked neurodegeneration of temporal and possibly frontal lobe structures, and that response deficiencies could reflect involvement of motor areas.
Relationship between Growth Hormone Responses to Apomorphine and CSF Homovanillic Acid Levels in Dementia of the Alzheimer Type
Authors: Balldin Jan , Berggren Ulf , Gottfries Carl Gerhard , Lindstedt Göran
Published: August 2007

The possible relationship between growth hormone (GH) responses to the dopamine (DA) agonist apomorphine (APO; 0.24 mg i.v.) and CSF concentrations of the monoamine metabolites was investigated in 15 patients with dementia of the Alzheimer type (DAT). A significant negative correlation was found between the CSF concentrations of homovanillic acid (HVA) and the maximum APO-stimulated serum GH levels. Assuming that CSF HVA reflects central DA release and the GH response to APO reflects postsynaptic DA D2 receptor function, this finding suggests that low DA release is associated with upregulation of DA D2 in DAT.
Morbid Risk to First Degree Relatives of Neuropathologically Confirmed Cases of Alzheimer's Disease
Authors: Bierer Linda M. , Silverman Jeremy M. , Mohs Richard C. , Haroutunian Vahram , Li Ge , Purohit Dushyant , Breitner John C.S. , Perl Daniel P. , Davis Kenneth L.
Published: August 2007

One source of variance in familial aggregation studies in Alzheimer''s disease (AD) is proband diagnosis. In this study, the morbid risk of primary progressive dementia (PPD) was assessed in first degree relatives of 32 patients with clinically diagnosed AD (mean onset = 59.9 ± 7.2 years) whose diagnoses were confirmed at autopsy. The Alzheimer''s Disease Risk Questionnaire and the Dementia Questionnaire were administered to multiple family informants by trained raters blind to the probands'' clinical and neuropathologic diagnoses. Morbid risk for PPD was analyzed using the Kaplan-Meier life-table method. The estimated cumulative risk of PPD in first degree relatives (n = 159; age ≧: 45) was estimated to be 48.8 ± 11.3% by age 86. The risk estimate for affected siblings (n = 96; age ≧ 45) reached 54.9 ± 20.7 % by age 78. These figures are consistent with those calculated for most cohorts of relatives of clinically selected AD probands lacking autopsy confirmation of diagnosis. Although based on a relatively small sample, this series is the first morbid risk analysis to employ clinically diagnosed probands with neuropathologic confirmation of AD.
MRI Finding in an Offspring of an Individual with Familial 2 Alzheimer's Disease
Authors: Sagawa Katsuo , Kawakatsu Shinobu , Totsuka Shiro
Published: August 2007

An at risk offspring of an individual with familial Alzheimer''s disease showed a white matter lesion on magnetic resonance imaging. This finding might appear in some individuals with Alzheimer''s disease before its clinical onset.
Principal Component Analysis of the GBS Scale
Authors: Nyth Anna Lena , Bråne Görel
Published: August 2007

Principal component analysis of the Gottfries-Bråne-Steen (GBS) scale was performed. GBS ratings of 221 consecutive patients with suspected or mild to severe dementia formed the basis for the analysis. A four-factor solution and varimax rotation was selected which accounted for 64.5 % of the variance. The components were called Impaired Orientation and Memory, Impaired Ability to Perform Activities of Daily Living, Depression-Anxiety and Impaired Attention and Motivation. This empirically based organization of 22 of the 26 items was used to generate subscales (GBS-F scales). The internal consistency of each of the GBS-F scales was estimated in 2 other samples and was found satisfactory. The GBS-F scales may be used in studies of the course of various dementia disorders and of the efficacy of drug therapy and other interventions aimed at modifying the course of a dementia disorder.
Increased Proteolytic Activity in Erythrocytes from Patients with Alzheimer's Disease
Authors: Karlsson J.O. , Blennow K. , Holmberg B. , Janson I. , Karlsson I. , Nilsson E. , Wallin A. , Gottfries C.G.
Published: August 2007

Ca-independent and Ca-dependent proteolytic activity were significantly higher in erythrocytes from male patients with Alzheimer''s disease compared to control subjects. The level of calpastatin, an endogenous inhibitor of the proteolytic enzyme calpain, was lower in male patients with Alzheimer''s disease. The small changes observed in the female group were not statistically significant. Control male subjects had significantly higher levels of calpastatin compared to female controls. The observed changes in the calpain/calpastatin system of erythrocytes may be caused by a general dysregulation of Ca homeostasis in cells of Alzheimer patients and may lead to calpain-induced pathological changes.
MAO A and B Immunoreactivity in the Hippocampus, Temporal Cortex and Cerebellum of Normal Controls and of Patients with Senile Dementia of the Alzheimer Type (Part 1 of 2)
Authors: Zetzsche T. , Chan-Palay V.
Published: August 2007

The distribution of MAO A and B immunoreactivity was studied in the postmortem hippocampus, cerebellum and temporal cortex of normal controls and in patients with senile dementia of the Alzheimer type (SDAT). In normal control, neurons, glia cells, cellular processes and the walls of blood vessels were found to be MAO-immunoreactive (MAO-i). In the hippocampus of control cases, a subpopulation of small nonpyramidal neurons was MAO A-i. In addition, the somata of granule and pyramidal cells were densely surrounded by MAO B-i cellular processes. In the cerebellum, fine MAO A and B-i cellular processes and small varicosities were found in the cortex and in the dentate nucleus. In the normal temporal cortex, glia cells and cellular processes were MAO A-i and MAO B-i in all lamina. In SDAT, some changes of MAO immunoreactivity were encountered in all of the examined brain areas. The hippocampal MAO A-i neurons were well preserved in the dentate gyrus. However, large MAO B-i glia cells were found in the Ammon's horn, subiculum and entorhinal cortex, where they formed cell clusters or patches with increased MAO B immunoreactivity. Bodian-stained sections of the same hippocampi showed neuritic plaques in a similar number and regional distribution as the patches of increased MAO B immunoreactivity. In the cerebellar cortex of SDAT patients, plexuses of thick MAO A-i processes as well as patches of increased MAO B immunoreactivity with clusters of large MAO B-i glia cells were found. In the temporal cortex of SDAT cases, proliferation of large MAO B-i glia cells was detected. These glia cells formed numerous patches of increased MAO B immunoreactivity which were predominantly found in the upper cortical layers, similar to the distribution of neuritic plaques.
Changes of High-Affinity Choline Uptake in the Hippocampus of Old Rats after Long-Term Administration of Two Nootropic Drugs (Tacrine and Ginkgo biloba Extract)
Authors: Krištofiková Z. , Benešová O. , Tejkalová H.
Published: August 2007

The effect of tacrine (THA), the cholinesterase inhibitor, and Ginkgo biloba extract (EGb) on the sodium-dependent high-affinity choline uptake (HACU) into hippocampal synaptosomes was studies in vivo in model experiments after long-term administration in old rats (THA 5 or 10 mg/kg/day p.o. for 3 months; EGb 50 or 100 mg/kg/day p.o. for 30 days) and in vitro tests. EGb increased HACU both in vivo and in vitro experiments. On the contrary, THA induced a decrease of HACU under both conditions, suggesting a negative impact on the cholinergic neuronal activity.
The Effects of Moclobemide on Psychomotor Performance and Cognitive Function in the Elderly
Authors: Hindmarch I. , Kerr J.S. , Fairweather D.B.
Published: August 2007

Behavioural toxicity is a side-effect of many psychoactive drugs and can be defined as the extent to which a centrally acting compound disrupts those abilities necessary for the performance of the psychomotor and cognitive tasks of everyday life. Moclobemide is a novel antidepressant which functions by the reversible inhibition of monoamine oxidase-A (MAO-A). In an elderly population moclobemide was shown to be no different from placebo in tests of psychomotor performance and cognitive function. As a reversible MAO inhibitor with a neutral profile of behavioural toxicity, this compound may make a valuable contribution to the treatment of depression in the elderly.
Vascular Adhesion Molecules in Atherosclerosis
Authors: Galkina Elena , Ley Klaus
Published: August 2007

Numerous reports document the role of vascular adhesion molecules in the development and progression of atherosclerosis. Recent novel findings in the field of adhesion molecules require an updated summary of current research. In this review, we highlight the role of vascular adhesion molecules including selectins, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule1 (ICAM-1), PECAM-1, JAMs, and connexins in atherosclerosis. The immune system is important in atherosclerosis, and significant efforts are under way to understand the vascular adhesion molecule–dependent mechanisms of immune cell trafficking into healthy and atherosclerosis-prone arterial walls. This review focuses on the role of vascular adhesion molecules in the regulation of immune cell homing during atherosclerosis and discusses future directions that will lead to better understanding of this disease.
USF1 Contributes to High Serum Lipid Levels in Dutch FCHL Families and U.S. Whites With Coronary Artery Disease
Authors: Lee Jenny C. , Weissglas-Volkov Daphna , Kyttälä Mira , Sinsheimer Janet S. , Jokiaho Anne , de Bruin Tjerk W.A. , Lusis Aldons J. , Brennan Marie-Luise , van Greevenbroek Marleen M.J. , van der Kallen Carla J.H. , Hazen Stanley L. , Pajukanta Päivi
Published: August 2007

Objective—

Familial combined hyperlipidemia (FCHL) characterized by high serum total cholesterol and/or triglycerides (TGs) is a common dyslipidemia predisposing to coronary artery disease (CAD). Recently, the upstream transcription factor 1 (
USF1
) was linked and associated with FCHL and TGs in Finnish FCHL families. Here we examined the previously associated rs3737787 SNP in extended Dutch FCHL families (n=532) and in a cohort of US subjects who underwent diagnostic coronary angiography (n=1533).

Methods and Results—

In males of the Dutch FCHL families, we observed significant sex-dependent associations between the common allele of rs3737787 and FCHL, TGs, and related metabolic traits (
P
=0.02 to 0.006). In the U.S. Whites, sex-dependent associations with TGs and related metabolic traits were observed for the common allele of rs3737787 in males (
P
=0.04 to 0.02) and rare allele in females (
P
=0.05 to 0.002). This intriguing relationship was further supported by the highly significant genotype
x
sex interactions observed for TGs in the Dutch and TGs and body mass index (BMI) in U.S. White subjects with CAD (
P
=0.0005 to 0.00004).

Conclusion—

These data show that
USF1
influences several cardiovascular risk factors in a sex-dependent manner in Dutch FCHL families and U.S. Whites with CAD. A significant interaction between sex and genotype was shown to affect TGs and BMI.