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J Kril

Publications and source records attributed to J Kril.

17 recordsLinked to original sources
PubMed2006

Investigation of Alzheimer's disease-related pathology in community dwelling older subjects who committed suicide.

BACKGROUND: Older people have a higher risk of completed suicide than any other age group worldwide. The contribution of neurodegenerative disease to this risk remains controversial. AIMS: To investigate prevalence of Alzheimer's disease-related (AD) pathology in older suicide victims. METHODS: Ratings of AD pathology using Braak and CERAD protocols were compared in 143 community-dwelling suicide victims aged 65 years or more and 59 motor vehicle accident victims autopsied at the request of an Australian Coroner's Court. RESULTS: There were no significant differences in plaque score or neurofibrillary tangle staging between suicide and control groups. None of the subjects with a history of dementia had neuropathologically confirmed AD. CONCLUSIONS: Our study is the second and largest investigation of the prevalence of AD neuropathology in the elderly suicide population. Unlike the previous study, we did not find an increased prevalence of AD neuropathology despite a history of dementia in 6.3%, implicating other pathologies such as Lewy Body or Vascular dementia in the aetiology of dementia in elderly suicide victims.

Accidents, Traffic↗
PubMed2003

Survival in frontotemporal dementia.

OBJECTIVES: To establish survival in patients with pathologically confirmed frontotemporal dementia (FTD) and to determine whether clinical or pathologic subtype affects prognosis. METHODS: The authors reviewed the presenting clinical features of 61 patients with dementia and pathologically confirmed FTD studied in Sydney (n = 31) and Cambridge (n = 30) over a 10-year period. Data were available on time of symptom onset, diagnosis, institutionalization, and death. Cases were classified pathologically as tau-positive and tau-negative. RESULTS: Of the 61 patients with FTD, 26 presented with frontal variant (fvFTD), 9 with semantic dementia, 8 with progressive nonfluent aphasia (PNFA), 9 with associated motor neuron disease (FTD-MND), and 9 with corticobasal degeneration features. There was no difference between the groups in age at symptom onset (overall mean 58.5 +/- 7.8 years), but at diagnosis the PNFA (68.3 +/- 2.7) group was significantly older than the fvFTD (59.9 +/- 7.4) and FTD-MND (57.7 +/- 7.9) groups. The median survival from symptom onset and from diagnosis was 6 +/- 1.1 years (95% CI) for fvFTD and 3 +/- 0.4 years for FTD-MND. Survival across subgroups was equivalent except for the FTD-MND group, which had significantly shorter survival. Cases with tau-positive pathology had an older age at onset and a significantly better prognosis: median survival 9.0 +/- 0.9 years vs 5.0 +/- 1.1 years. CONCLUSIONS: FTD is a malignant disorder with limited life expectancy. FTD-MND has the shortest duration both before and after diagnosis. Tau-positivity is associated with a more slowly progressive form of FTD.

Aged↗
PubMed2002

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria.

The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

Alzheimer Disease↗
PubMed2000

Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia.

The specific neural substrate underlying the amnesia in alcoholic Korsakoff's psychosis is poorly defined because of the considerable brain damage found in many non-amnesic alcoholics, particularly those with Wernicke's encephalopathy. Using operational criteria to identify alcoholics with and without Korsakoff's psychosis, we have shown that many of the cortical and subcortical regions involved in the encoding and retrieval of episodic memory are either unaffected (hippocampus) or damaged to the same extent (prefrontal cortex and the cholinergic basal forebrain) in both amnesic and non-amnesic alcoholics. In the present study we analysed the diencephalic regions involved in episodic memory to determine the neural substrate for the amnesia observed in alcoholic Korsakoff's psychosis. The number of neurons in spaced serial sections containing the hypothalamic mamillary nuclei and the anterior and mediodorsal thalamic nuclei was estimated using unbiased stereological techniques. Neurodegeneration of the hypothalamic mamillary nuclei and the mediodorsal thalamic nuclei was substantial in both non-amnesic and amnesic alcoholics with Wernicke's encephalopathy. However, neuronal loss in the anterior thalamic nuclei was found consistently only in alcoholic Korsakoff's psychosis. This is the first demonstration of a differentiating lesion in alcoholic Korsakoff's psychosis and supports previous evidence that degeneration of thalamic relays are important in this memory disorder.

Aged↗
PubMed1995

Motor neuron disease: a primary disorder of corticomotoneurons?

It has been suggested that the primary site of damage in motor neuron disease (MND) is the cortical motor neuron, with secondary degeneration of spinal motor neurons. To test this hypothesis, we sought to determine if loss of corticomotoneurons in MND precedes spinal motor neuron loss. The density of corticomotoneurons was measured in 18 MND and 9 control cases using 10-microns horizontal sections of motor cortex in the hand/arm region. The density of spinal motor neurons was measured in 10-microns transverse sections of the lower cervical spinal cord. Corticomotoneuron and spinal motor neuron densities were decreased in MND cases compared to controls, but in MND cases there was poor correlation (r2 = 0.06) between corticomotoneuron and spinal motor neuron densities. The results indicate that corticomotoneuron and spinal motor neurons are lost at different rates in different MND patients, and that corticomoteneuron loss is unlikely to be a primary event in MND.

Adult↗
PubMed1994

An introduction to alcohol-induced brain damage and its causes.

The aim of the symposium on alcohol-induced brain damage is to review current opinion and recent advances concerning factors which are thought to play a significant role in this disorder. The three principal factors are: alcohol specific neurotoxicity, associated vitamin B1 (thiamine) deficiency (the Wernicke-Korsakoff syndrome) and liver failure secondary to alcoholic cirrhosis. There is a complex interaction of these and other factors and it is difficult to dissect out the relative importance of each in the pathogenesis of alcohol-related brain damage. Moreover recent molecular and biochemical studies suggest that several of these factors may have pathogenetic mechanisms in common-for example, excitotoxicity, mitric oxide and free radicals. The application of new technologies in neuropathological studies of carefully selected groups of alcoholic cases is beginning to reveal a far more complex pattern of damage than current view holds. Quantitative morphometry and immunohistochemistry can be combined to create three dimensional images of various anatomical regions of the brain together with detailed analyses of neuronal counts, sizes and neurochemical type. In the Wernicke-Korsakoff syndrome (WKS) there is good evidence (in support of neuropsychological and neuroradiological data) to suggest that specific populations of neurons are damaged in cortical and subcortical regions. In those cases with the WKS there is also evidence of pathological damage in cortical and subcortical regions other than the well described periventricular distributions. These more detailed studies provide us with a more comprehensive understanding of alcohol-related brain damage.

Alcoholism↗
PubMed1991

If you drink your brain will shrink. Neuropathological considerations.

Recent quantitative neuropathological analyses of the effects of alcohol on the central nervous system have revealed some interesting findings. CT scan studies have suggested shrinkage of the brain in alcoholics and this has been confirmed pathologically. Brain shrinkage relates to a loss of the white matter rather than the grey. However the cortical grey matter is not spared. There is a selective loss of neurones from the frontal region and in this and other cortical regions (motor and cingulate) there is shrinkage of the neuronal soma. This is reflected in a retraction of neuronal dendritic arbor which could account for a loss of white matter but does not explain the reversible brain shrinkage that sometimes follows prolonged abstinence. These studies were extended to specific population groups including moderate drinkers, female alcoholics and alcoholics with cirrhosis of the liver and the Wernicke-Korsakoff syndrome.

Alcoholism↗
PubMed1989

Patterns of neuronal loss in the cerebral cortex in chronic alcoholic patients.

A loss of neurones from the frontal cortex of chronic alcoholic patients has recently been documented. In addition to this loss of neurones there was found to be a reduction in the mean size of the neuronal soma in both the superior frontal and motor cortices. This could be explained on the basis of a selective loss of larger neurones rather than a general shrinkage of all neurones. This population of large neurones (greater than 90 microns 2) has been recognised as being more vulnerable in both Alzheimer's disease and the normal ageing process. Neurones in 2 size categories (41-90 microns 2 and greater than 90 microns 2) were counted in the superior frontal and motor cortices of age- and sex-matched controls and alcoholics. There was found to be a significant reduction in the number of large neurones in the superior frontal cortex, whilst no change in number was seen in the motor cortex. The possibility that neurones in particular layers of the cortex are more severely affected in alcohol abuse was also considered. The cortex was divided into 3 layers and the number of neurones and glia in each determined. No pattern of regional neuronal loss could be distinguished.

Alcoholism↗
PubMed1988

Does a "moderate" alcohol intake damage the brain?

A range of volumetric and neurochemical analyses were carried out on the brains of 14 "moderate" drinkers. These data were compared with previous studies from controls and alcoholics. Volumetric measurements consistently suggest a loss of cerebral tissue although the differences were not statistically significant. Changes in the lipid and water content of the white matter were noted and the significance of these changes in relation to the pathogenesis of reversible brain shrinkage caused by alcohol abuse is discussed.

Alcohol Drinking↗
PubMed1987

Are we drinking our neurones away?

A quantitative neuropathological necropsy study of the human cerebral cortex showed that the number of cortical neurones in the superior frontal cortex in chronic alcoholic patients is significantly reduced compared with that in controls matched for age and sex. The number of neurones in the motor cortex did not differ significantly between the controls and alcoholics, but in both cortical regions there was evidence that alcoholic patients had smaller (shrunken) neurones than controls. Further studies are necessary to identify other regions of the cerebral cortex that are selectively damaged in brain damage associated with alcohol.

Adult↗
PubMed1987

A quantitative histological study of the cerebellar vermis in alcoholic patients.

A quantitative histological study was made of the cerebellar vermis in 10 male alcoholic and 8 age-matched control cases. The mean Purkinje cell loss was 21% in the alcoholic group. The small rostral and caudal lobes were most severely affected. The mean Purkinje cell density per unit length of foliae showed similar changes. Histological measurements of the area of the molecular, granular and medullary layers of the cerebellar vermis showed that the molecular layer varied in the degree of shrinkage between lobes (from 11 to 39%) while the granular layer showed a consistent shrinkage (9 to 10%). The molecular layer appears to be the most vulnerable region in chronic alcoholics. Brains taken from patients with Wernicke's encephalopathy had particularly low Purkinje cell counts and a large pericerebral space. Nutritional deficiency would seem to be an important factor in the causation of the observed neuropathology, with liver disease playing a lesser role. Evidence that repeated alcohol withdrawal can lead to further brain disturbances is reviewed.

Aged↗
PubMed1985

Brain atrophy in chronic alcoholic patients: a quantitative pathological study.

There are essentially no objective neuropathological data on brain atrophy in chronic alcoholic patients despite numerous neuroradiological studies which show a high incidence of shrinkage or atrophy. Therefore measurements were made of the intracranial volume (ICV) and brain volume (BV) in a necropsy study of 25 chronic alcoholic patients and 44 controls. The pericerebral space (PICS) was calculated according to the formula (formula; see text) The PICS will increase in patients with brain atrophy since the ICV remains constant throughout life. The mean PICS value was 8.3% in controls, 11.3% in the alcoholic group, 14.7% in alcoholics with superimposed Wernicke's encephalopathy (thiamine deficiency) and 16.2% in those alcoholics with associated liver disease. Thus there was a statistically significant loss of brain tissue in chronic alcoholic patients which appeared to be more severe in those with associated nutritional vitamin deficiencies or alcoholic liver disease.

Adult↗
PubMedDate not supplied

Progression of neurological disease in thiamin-deficient rats is enhanced by ethanol.

The clinical and neuropathological consequences of either ethanol consumption or thiamin deficiency or both were examined in Wistar rats aged nine weeks divided into five groups and fed one of the following diets: a thiamin-replete (control) diet (A): a thiamin-fortified diet with water (B) or 15% ethanol (C); or a thiamin-deficient diet with water (D) or 15% ethanol (E). Rats fed diets A, B or C for 35 weeks showed no clinical signs of neurological disease at any stage and no significant brain pathology when harvested. Rats fed diets D and E progressed through a common sequence of clinical signs of neurological disease typical of acute thiamin deficiency, viz loss of coat condition, ataxia, opisthotonus and ultimately death within 10-23 weeks. The onset and progression of these stages of neurological disease were significantly earlier and faster (p less than 0.001 for proportion of opisthotonic and ataxic animals at weeks 10 and 15) in the thiamin-deficient rats that received ethanol than in those that did not. At death, the brain pathology in these two groups was limited and similar.

Animals↗
PubMedDate not supplied

Alzheimer's disease and inflammation: a review of cellular and therapeutic mechanisms.

1. Of the neurodegenerative diseases that cause dementia, Alzheimer's disease (AD) is the most common. Three major pathologies characterize the disease: senile plaques, neurofibrillary tangles and inflammation. We review the literature on events contributing to the inflammation and the treatments thought to target this pathology. 2. The senile plaques of AD consist primarily of complexes of the beta-amyloid protein. This protein is central to the pathogenesis of the disease. 3. Inflammatory microglia are consistently associated with senile plaques in AD, although the classic inflammatory response (immunoglobulin and leucocyte infiltration) is absent. beta-Amyloid fragments appear to mediate such inflammatory mechanisms by activating the complement pathway in a similar fashion to immunoglobulin. 4. Epidemiological studies have identified a reduced risk of AD in patients with arthritis and in leprosy patients treated with anti-inflammatory drugs. Longitudinal studies have shown that the consumption of anti-inflammatory medications reduces the risk of AD only in younger patients (< 75 years). 5. There is a considerable body of in vitro evidence indicating that the inflammatory response of microglial cells is reduced by non-steroidal anti-inflammatory drugs (NSAID). However, no published data are available concerning the effects of these medications on brain pathology in AD. 6. Cyclo-oxygenase 2 enzyme is constitutively expressed in neurons and is up-regulated in degenerative brain regions in AD. Non-steroidal anti-inflammatory drugs may reduce this expression. 7. Platelets are a source of beta-amyloid and increased platelet activation and increased circulating beta-amyloid have been identified in AD. Anti-platelet medication (including NSAID) would prevent such activation and its potentially harmful consequences. 8. Increased levels of luminal beta-amyloid permeabilizes the blood-brain barrier (BBB) and increases vasoconstriction of arterial vessels, paralleling the alterations observed with infection and inflammation. Cerebral amyloidosis is highly prevalent in AD, compromising the BBB and vasoactivity. Anti-inflammatory medications may alleviate these problems.

Aged↗
PubMedDate not supplied

Intracranial cavity volumes: a new method and its potential applications.

Variations of brain weights and volumes often reflect pathological states. However, these parameters are more meaningful when related to intracranial volume. The most useful derived parameter is the difference between intracranial volume and brain volume expressed as a percentage (potential intracranial space). In patients with cerebral atrophy the potential intracranial space will be large, whereas in patients with space occupying lesions or brain swelling the potential intracranial space will shift towards 0%. Previously described techniques to determine intracranial volume have been unsatisfactory for routine application in the autopsy room. The technique described herein is based on the production of a permanent polyurethane cast of the cranial cavity. The casts can be formed in about 20 min with little modification of standard autopsy technique. Duplicate casts were made in twenty-seven unselected cases and in all cases there was less than 2% error in duplicate cast volumes. The cast provides a permanent record of the size and shape of the cranial cavity and can be used to determine intracranial volume or other intracranial dimension. The usefulness of the derived parameter, potential intracranial space, is evident in some of the cases studied.

Adult↗