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 identified by fluorescence micro...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 identified 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.
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...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.
EEG indicators were correlated with clinical items in 174 patients with dementia diagnoses based on the DSM-III-R criteria. The patients' clinical symptomatologies were presented as regional brain syndromes, i.e. parieta...EEG indicators were correlated with clinical items in 174 patients with dementia diagnoses based on the DSM-III-R criteria. The patients' clinical symptomatologies were presented as regional brain syndromes, i.e. parietal lobe, frontal lobe, subcortical and global (nonregional) syndromes. The EEGs were abnormal in 87% of the cases. The typical abnormalities consisted of diffusely distributed slow wave activity. A significant correlation was found between the degree of slow wave abnormality and the degree of dementia. The results of the statistical analysis also suggest that EEG slow wave activity in dementia primarily reflects parietal lobe dysfunction. No association seems to exist between EEG slow wave activity and frontal lobe dysfunction.
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 v...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.
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...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.
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...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.
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...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.
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 or...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.
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...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 beta-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 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 demen...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. 'Fuzzylogic' 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.
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 pa...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.
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 de...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 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.
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...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.
UNLABELLED: Regional cerebral blood flow (rCBF) was studied in patients with Alzheimer's disease (AD) before and after 14 months of tacrine treatment. The treated group was compared with an identical reference group of u...UNLABELLED: Regional cerebral blood flow (rCBF) was studied in patients with Alzheimer's disease (AD) before and after 14 months of tacrine treatment. The treated group was compared with an identical reference group of untreated AD patients. At baseline the two groups showed an identical rCBF and mean hemispheric blood flow. After 14 months the tacrine-treated patients showed a stable rCBF level and a significant increase in rCBF in the central-parietal regions, compared to the untreated reference group, who showed typical AD reductions in rCBF in these regions. CLINICAL OUTCOME: 7 of 9 patients in the tacrine group were clinically unchanged or slightly improved during the study time. In the untreated group 8 of 11 patients had deteriorated in clinical assessments and none had improved. Long-term tacrine treatment in Alzheimer's disease may delay the progression of symptoms.
Potassium (K+) channel dysfunction in fibroblasts was recently proposed as a potential diagnostic marker for Alzheimer disease (AD). We utilized a microspectrofluorometric method with Fura-2AM to measure intracellular fr...Potassium (K+) channel dysfunction in fibroblasts was recently proposed as a potential diagnostic marker for Alzheimer disease (AD). We utilized a microspectrofluorometric method with Fura-2AM to measure intracellular free calcium ([Ca2+]i) following depolarization with the K+ channel blocker tetraethylammonium (TEA) in seven AD and seven control fibroblast cultures. Contrary to our expectation, 43% of the AD and 36% of the control fibroblast plated coverglasses responded with an increase in [Ca2+]i on addition of 100 mM TEA. The data suggest that the TEA-elicited [Ca2+]i response is not a useful AD screening test.
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 s...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 lability 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-preserved cerebrum. We discuss the relationship between the psychiatric symptoms and pathologic findings of brain stem tegmentum.
The authors reviewed historical data in the development of THA, as well as recent data on its pharmacological properties and therapeutic effects on cognitive dysfunction. A medline search was conducted to identify the tr...The authors reviewed historical data in the development of THA, as well as recent data on its pharmacological properties and therapeutic effects on cognitive dysfunction. A medline search was conducted to identify the trials conducted with THA in Alzheimer's disease (AD) patients. The findings seem to lend support to some palliative action of THA, especially at higher doses, but in these doses about 2/3 of the patients experience significant adverse reactions. The significance of these findings is discussed, with emphasis on the their relevance for the management of AD patients.
It has been increasingly appreciated in the last decade that the neocortex of the Alzheimer's disease brain is characterized by a widespread neuritic dystrophy, spatially distinct from that observed surrounding neuritic...It has been increasingly appreciated in the last decade that the neocortex of the Alzheimer's disease brain is characterized by a widespread neuritic dystrophy, spatially distinct from that observed surrounding neuritic amyloid plaques. The nature and significance of this cortical neuritic dystrophy and its possible pathogenesis are the topics of this review. It may represent a regenerative sprouting response of neurons to partial deafferentation following cell loss; alternatively it may reflect a primary aberrant growth phenomenon leading to cell loss. Such changes could result from derangement of neurite growth-promoting and growth-inhibitory factors in the Alzheimer's disease brain.
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 s...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.
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. F...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.(ABSTRACT TRUNCATED AT 250 WORDS)