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...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.
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 r...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.
The reason for the occurrence of Lewy body disease (LBD) in Alzheimer's disease (AD) patients is unknown. If brains from etiologically different AD groups differ in their tendency to develop cortical Lewy bodies, the con...The reason for the occurrence of Lewy body disease (LBD) in Alzheimer's disease (AD) patients is 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.
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 d...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.
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 ventricl...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 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 d...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.
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 A...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.
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 nursi...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.
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...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.
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 de...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.
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 cli...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.
Neurons in the nucleus basalis of Meynert (NBM) were analyzed morphometrically in 21 rhesus monkeys ranging in age from 9 to 33 years. Numbers of cholinergic neurons were similar across all ages at several NBM levels in...Neurons in the nucleus basalis of Meynert (NBM) were analyzed morphometrically in 21 rhesus monkeys ranging in age from 9 to 33 years. Numbers of cholinergic neurons were similar across all ages at several NBM levels in either Nissl-stained paraffin sections or sections processed immunocytochemically for nerve growth factor receptor (p75LNGFr). Size of NBM neurons was larger in aged monkeys than young monkeys at all NBM levels, particularly in the most posterior subdivision. A subset of monkeys were behaviorally characterized shortly before death, and partial correlation analyses indicated that increased age was associated with declines in recognition memory, visuospatial orientation, and reaction time. Controlling for age, spatial memory and concurrent discrimination abilities were associated with lower cell number in intermediate NBM. Numbers of neurons in anterior NBM did not correlate with any behavioral measure. These observations indicate that numbers of NBM cholinergic neurons are stable with age, that NBM neurons become hypertrophic in older animals, and that morphometric indices of cholinergic neurons are associated with cognitive function.
Despite the close morphological association of beta-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 amy...Despite the close morphological association of beta-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 A beta 1-40, 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.
The density of diffuse, primitive, classic and compact beta-amyloid (beta/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,...The density of diffuse, primitive, classic and compact beta-amyloid (beta/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, beta/A4 deposits were absent in the hippocampus but in 8/14 cases they were present in the adjacent cortical regions. Variation in beta/A4 deposition in the non-demented cases was large and overlapped with that of the AD cases. The ratio of mature to diffuse beta/A4 deposits was greater in the non-demented than in the AD cases. In both the non-demented cases and AD, the beta/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 beta/A4 pathology between the modular units of the cortex and into the hippocampus could be important factors in the development of AD.
Seven female patients with mild to moderate dementia of the Alzheimer type (DAT) were treated with long-term, low-dose estrogen replacement therapy (ERT) over a period of 5-45 months. Five of the 7 patients were cases wh...Seven female patients with mild to moderate dementia of the Alzheimer type (DAT) were treated with long-term, low-dose estrogen replacement therapy (ERT) over a period of 5-45 months. Five of the 7 patients were cases who had responded well to short-term ERT with 1.25 mg/day of conjugated equine estrogens (CEE) for 6 weeks. The 7 patients from 56 to 77 years of age received 0.625 mg/day of CEE for 21 days, followed by a pause of 7 days. A 28-day cycle of low-dose ERT was performed repeatedly. In 4 cases, these patients received 5 mg/day of medroxyprogesterone acetate (MPA) during the last 10-12 days of estrogen treatment. Therapeutic efficacy of estrogen was evaluated by psychometric assessments such as the Mini-Mental State Examination (MMSE) and the Hasegawa Dementia Scale (HDS) and a behavior rating scale of the Gottfries-Bråne-Steen geriatric rating scale (GBS). The MMSE and HDS evaluations were performed principally once in 2-4 weeks. In 4 out of the 7 patients, the MMSE and HDS scores were elevated above the pretreatment levels during ERT. The termination of ERT resulted in a decrease in both scores. Furthermore, the GBS scores and daily activities of the same 4 patients were improved during ERT. In these 4 patients cognitive functions were markedly improved throughout the treatment period, while the other 2 patients responded moderately well and another patient did not respond at all. These observations suggest that long-term, low-dose ERT improves cognitive functions, dementia symptoms and daily activities in women with mild to moderate DAT.(ABSTRACT TRUNCATED AT 250 WORDS)
An 81-year-old man presented with psychotic episodes involving the delusion that his wife had been replaced by a closely resembling double (the so-called Capgras delusion). A comprehensive neuropsychological investigatio...An 81-year-old man presented with psychotic episodes involving the delusion that his wife had been replaced by a closely resembling double (the so-called Capgras delusion). A comprehensive neuropsychological investigation revealed no signs of dementia at that time, but in the subsequent course the patient became demented and died 5 years later. Neuropathological and neurochemical examination displayed many diffuse plaques in the cortex that escaped detection by Congo-red but were clearly demonstrated by antibodies raised to beta-amyloid protein. Neurofibrillary tangles were absent in the cortex. Antiubiquitin immunohistochemistry revealed some cortical and subcortical Lewy bodies. The hippocampus and the majority of the nigral cells were intact. However, in the frontal and parietal white-matter many small lacunar infarcts were found due to arteriosclerotic and hypertensive vessel wall changes. Though the etiology of psychotic symptoms in the context of dementia is complex, this study shows the possible significance of white-matter lesions in the pathogenesis of delusions and subsequent dementia.
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 parie...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 findings suggest that the parietal cortex is involved in the cognitive impairment in patients with Parkinson's disease.
Twenty patients with Alzheimer's 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 crit...Twenty patients with Alzheimer's 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.
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 degene...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.
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 alumini...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 micrograms/g dry bone) versus the non-demented group (18.2 +/- 7.37 micrograms/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.