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N C Fox

Publications and source records attributed to N C Fox.

At least 73 records · Page 4Linked to original sources
PubMed1998

Presymptomatic cognitive deficits in individuals at risk of familial Alzheimer's disease. A longitudinal prospective study.

A longitudinal study of asymptomatic individuals at risk of autosomal dominant familial Alzheimer's disease was performed to assess the earliest clinical and neuropsychological features of the disease. Over a 6-year period, 63 subjects underwent serial assessments. During the study, 10 subjects developed symptoms of episodic memory loss and subsequently progressed to fulfil criteria for possible or probable Alzheimer's disease. The mean time (+/-SD) from first assessment to the appearance of symptoms was 2.6+/-1.4 years. The subjects who remained well were similar to those who became clinically affected in terms of age, family history and initial Mini-Mental State Examination. Individuals who later became clinically affected already had significantly lower verbal memory (P=0.003) and performance IQ (P=0.030) scores at their first assessment, when they were ostensibly unaffected. Subsequent assessments showed progressive decline in multiple cognitive domains. Blinded assessment of serial imaging revealed the appearance of diffuse cerebral and medial temporal lobe atrophy in subjects only once they were clinically affected. These findings imply that in familial Alzheimer's disease cognitive decline predates symptoms by several years and that verbal memory deficits precede more widespread deterioration. This may have implications for the detection and treatment of Alzheimer's disease at an early stage.

Alzheimer Disease↗
PubMed1998

MR image texture analysis applied to the diagnosis and tracking of Alzheimer's disease.

We assess the value of magnetic resonance (MR) image texture in Alzheimer's disease (AD) both as a diagnostic marker and as a measure of progression. T1-weighted MR scans were acquired from 40 normal controls and 24 AD patients. These were split into a training set (20 controls, 10 AD) and a test set (20 controls, 14 AD). In addition, five control subjects and five AD patients were scanned repeatedly over several years. On each scan a texture feature vector was evaluated over the brain; this consisted of 260 measures derived from the spatial gray-level dependence method. A stepwise discriminant analysis was applied to the training set, to obtain a linear discriminant function. In the test set, this function yielded significantly different values for the control and AD groups (p < 10(-4)) with only small group overlap; a classification rate of 91% was obtained. For the repeatedly scanned control subjects, the median increment in the discriminant function between successive scans of 0.12 was not significantly different from zero (p > 0.05); for the repeatedly scanned AD patients the corresponding median increment of 1.4 was significantly different from zero (p < 0.05). MR image texture may be a useful aid in the diagnosis and tracking of Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

Chromosome 14 familial Alzheimer's disease: the clinical and neuropathological characteristics of a family with a leucine-->serine (L250S) substitution at codon 250 of the presenilin 1 gene.

BACKGROUND: Seven affected members are described from a kindred with autosomal dominant familial Alzheimer's disease associated with a novel mutation in the presenilin 1 (PS1) gene on chromosome 14 that results in a leucine to serine substitution at codon 250 (L250S). METHOD: Clinical information on the pedigree was collected directly from family members including affected members and their carers and also from hospital records. RESULTS: Detailed clinical information was available on five members. All had an early age at onset with a median age of 52 (95% confidence interval (95% CI) 49.4-54.9). Age at onset varied between 49 and 56 years, with duration of illness varying between six years and 15 years. Myoclonus, depression, and psychosis were features of this pedigree; seizures were not reported. CONCLUSIONS: PS1 L250S familial Alzheimer's disease is an early onset form of Alzheimer's disease with clinical features similar to other reported familial Alzheimer's disease pedigrees, except that seizures were absent.

Age of Onset↗
PubMed1997

Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans.

Interactive algorithms are an attractive approach to the accurate segmentation of 3D brain scans as they potentially improve the reliability of fully automated segmentation while avoiding the labour intensiveness and inaccuracies of manual segmentation. We present a 3D image analysis package (MIDAS) with a novel architecture enabling highly interactive segmentation algorithms to be implemented as add on modules. Interactive methods based on intensity thresholding, region growing and the constrained application of morphological operators are also presented. The methods involve the application of constraints and freedoms on the algorithms coupled with real time visualisation of the effect. This methodology has been applied to the segmentation, visualisation and measurement of the whole brain and a small irregular neuroanatomical structure, the hippocampus. We demonstrate reproducible and anatomically accurate segmentations of these structures. The efficacy of one method in measuring volume loss (atrophy) of the hippocampus in Alzheimer's disease is shown and is compared to conventional methods.

Algorithms↗
PubMed1997

Clinicopathological features of familial Alzheimer's disease associated with the M139V mutation in the presenilin 1 gene. Pedigree but not mutation specific age at onset provides evidence for a further genetic factor.

Sixteen affected individuals are described from two families with early onset autosomal dominant familial Alzheimer's disease. A mutation at codon 139 in the presenilin 1 gene on chromosome 14 results in a methionine to valine substitution which cosegregates with the disease in these families. Onset of dementia was before the age of 50 years in all individuals. The ages at onset within each family were tightly clustered but were significantly different between the families; this difference could not be accounted for by apolipoprotein E status and suggests the existence of a further genetic factor that modifies age at disease onset. The pattern of cognitive decline was similar in both families: early memory loss (initially selective for verbal memory in some individuals) was followed soon after by loss of arithmetic skills while naming and object perception skills were relatively preserved. A speech production deficit was observed in three members of one family but not in the other. Seizures were common and usually predated by myoclonic jerks by a number of years. Serial MRIs showed progressive cortical atrophy with periventricular white matter change appearing 3-4 years into the disease. PET revealed parieto-temporal hypometabolism in all individuals scanned. The diagnosis of Alzheimer's disease was confirmed with typical histopathology in one individual from each family.

Adult↗
PubMed1997

The boundary shift integral: an accurate and robust measure of cerebral volume changes from registered repeat MRI.

We propose the boundary shift integral (BSI) as a measure of cerebral volume changes derived from registered repeat three-dimensional (3-D) magnetic resonance (MR) [3D MR] scans. The BSI determines the total volume through which the boundaries of a given cerebral structure have moved and, hence, the volume change, directly from voxel intensities. We found brain and ventricular BSI's correlated tightly (r = 1.000 and r = 0.999) with simulated volumes of change. Applied to 21 control scan pairs and 11 scan pairs from Alzheimer's disease (AD) patients (mean interval 386 days) the BSI yielded mean brain volume loss of 1.8 cc (controls) and 34.7 cc (AD); the control group was tightly bunched (SD = 3.8 cc) and there was wide group separation, the group means differing by 8.7 control group standard deviations (SD's). A measure based on the same segmentation used by the BSI yielded similar group means, but wide spread in the control group (SD = 13.4 cc) and group overlap, the group means differing by 2.8 control group SD's. The BSI yielded mean ventricular volume losses of 0.4 cc (controls) and 10.1 cc (AD). Good linear correlation (r = 0.997) was obtained between the ventricular BSI and the difference in their segmented volumes. We conclude the BSI is an accurate and robust measure of regional and global cerebral volume changes.

Algorithms↗
PubMed1997

Slowing the progression of Alzheimer disease: monitoring progression.

The search for biologic markers of Alzheimer disease (AD) progression has thus far had limited success. A technique is described, involving magnetic resonance imaging, that can be used to follow the progress of brain atrophy and hence the loss of neuronal tissue. It involves acquisition of three-dimensional images of the brain on two consecutive occasions and their precise co-registration so as to assess the loss of tissue volume over time. Median loss of brain volume in a group of individuals with sporadic and familial AD ranged from about 5-20 ml/year compared to less than 2 ml/year for controls. Loss of cerebral tissue volume was also seen in two individuals from a pedigree with familial AD at a time when symptoms were only just apparent.

Alzheimer Disease↗
PubMed1996

Visualisation and quantification of rates of atrophy in Alzheimer's disease.

BACKGROUND: Definitive diagnosis of Alzheimer's disease requires histological examination of brain tissue. In life, brain atrophy can be visualised by computed tomography or magnetic resonance (MR) imaging, but the atrophy due to the disease is difficult to distinguish from that caused by normal ageing. We have investigated use of accurate positional matching (registration) and digital subtraction of serially acquired MR brain scans to allow determination of rates of global and regional atrophy. METHODS: This technique was applied to eleven patients with clinically diagnosed Alzheimer's disease and eleven age-matched controls. Each individual had two scans approximately 1 year apart; scan intervals were matched between the groups. FINDINGS: The median rate of atrophy was significantly greater in the Alzheimer's disease group than in the control group (12.3 [range 5.8 to 23.6] vs 0.3 (-1.2 to 1.7) mL per year; p < 0.0001). There was no overlap between the groups. Furthermore, three non-demented individuals at risk of familial Alzheimer's disease had scans 6-14 months apart and showed greater rates of volume loss than the controls; these three individuals have subsequently developed symptoms. INTERPRETATION: This technique may be useful for the diagnosis of Alzheimer's disease, the assessment of disease progression, and the evaluation of potential treatments.

Alzheimer Disease↗
PubMed1996

Atrophy of the hippocampal formation in early familial Alzheimer's disease. A longitudinal MRI study of at-risk members of a family with an amyloid precursor protein 717Val-Gly mutation.

The hippocampal formation (HF) is known from pathological and magnetic resonance imaging (MRI) studies to become severely atrophied in established Alzheimer's disease (AD). This study examined whether changes in the HF could also be detected in very early AD by scanning subjects at risk of developing familial AD (FAD). Five at risk members of a pedigree with the amyloid precursor protein (APP) 717 valine to glycine mutation underwent serial MRI scanning with volumetric measurement of the HF as well as neurological and neuropsychological assessments. Over a period of two years two subjects became clinically affected, a loss of up to 20% of the volume of the HF occurred in the two years over which symptoms first appeared. Asymmetrical HF atrophy was shown to have been present before the development of overt symptoms. This may have important implications for early diagnosis in AD more generally.

Adult↗
PubMed1996

Clinical features of sporadic and familial Alzheimer's disease.

Alzheimer's disease is increasingly seen as an heterogeneous disorder with a variety of molecular pathologies converging on a final common pathway of abnormal amyloid deposition and tau phosphorylation. These result in the appearance of the senile plaques and neurofibrillary tangles and in the subsequent development of a cortical dementia with a prominent memory deficit, reflecting the regional distribution of pathology. Age and mode of onset, additional neurological features and family history have all been used as a basis for classification. A family history has proved most robust with the identification of three genetic loci associated with autosomal dominant familial Alzheimer's disease (FAD). Genetically defined pedigrees are important for exploring the relationships between specific molecular pathology and clinical phenotype and, by following at risk individuals, identifying the earliest features.

Alzheimer Disease↗
PubMed1996

Presymptomatic hippocampal atrophy in Alzheimer's disease. A longitudinal MRI study.

The hippocampal formation (HF) is known from pathological and MRI studies to be severely atrophied in established Alzheimer's disease. However, it is unclear when the earliest changes in the HF occur. We performed a longitudinal study of asymptomatic individuals at risk of autosomal dominant familial Alzheimer's disease in order to assess presymptomatic changes in the HF. Seven at risk members of a familial Alzheimer's disease pedigree associated with the amyloid precursor protein 717 valine to glycine mutation underwent serial MR scanning and neuropsychological assessments over 3 years. These assessments were compared with results from 38 normal controls. During the study three at risk subjects became clinically affected. Volumetric measurement of the HF showed that asymmetrical atrophy developed in these subjects before the appearance of symptoms. Verbal and visual memory measures declined in parallel with hippocampal loss. A loss of up to 8% per annum of the volume of the HF occurred in the 2 years over which symptoms first appeared. These findings may have implications for early diagnosis of Alzheimer's disease.

Aged↗
PubMed1993

Comparison of nasal pressure support ventilation with nasal intermittent positive pressure ventilation in patients with nocturnal hypoventilation.

Nasal intermittent positive pressure ventilation (NIPPV) provides effective ventilatory support in patients with nocturnal hypoventilation. Nasal pressure support ventilation (NPSV), which only provides ventilation in response to patient triggering, may also be effective, simpler, and cheaper, but has not been evaluated. NIPPV and NPSV were compared in 12 patients with nocturnal hypoventilation, requiring domiciliary ventilatory support. The patients were studied on three consecutive nights, in random order: a control night without ventilation and a night on each mode of ventilatory support using the bilevel positive airway pressure (BiPAP) ventilator. Both NIPPV and NPSV significantly increased mean arterial oxygen saturation (SaO2) compared to the control night (NIPPV mean increase 4.1%; 95% confidence interval (CI) 2.2 to 6.1, NPSV 4.4%; CI 2.1 to 6.6) with no significant difference between the two modes. The percentage of the study night spent below 90% SaO2 was significantly reduced by both ventilator modes compared to the control night (median reduction on NIPPV 37%; CI -54 to -10, reduction on NPSV 31%; CI -53 to -9, with no significant difference between NPSV and NIPPV. NPSV was as effective as NIPPV in patients with nocturnal hypoventilation, which suggests that these patients are able to trigger the ventilator adequately. The lower cost of NPSV will make it accessible to more patients with chronic lung disease.

Female↗
PubMedDate not supplied

Brain atrophy progression measured from registered serial MRI: validation and application to Alzheimer's disease.

In this paper, we validate the brain boundary shift integral (BBSI) as a measure of brain atrophy and demonstrate its application in Alzheimer's disease (AD). Nineteen normal subjects and nine patients with AD underwent serial three-dimensional MRI (6- to 30-month scan intervals). Repeat studies were registered to the baseline studies. The accuracy of the BBSI was assessed by comparison with simulated atrophy and with segmentation; it was also tested for reproducibility, linearity, and its ability to discriminate patients with AD from healthy controls. The BBSI correlated closely with simulated volumes of atrophy (r = 1.000). The mean absolute difference between repeat measures was 1.51 ml or .13% of mean brain volume. Rates of atrophy from all 18 AD scan pairs were widely separated from those of all 31 control pairs. In matched subgroups, the mean (SD) annual rate of brain atrophy in nine controls was .24% (.32%), compared with 2.78% (.92%) in nine patients with AD. We conclude that the BBSI is a linear and highly reproducible measure of atrophy with potential uses in the early diagnosis and measurement of progression in Alzheimer's disease.

Alzheimer Disease↗
PubMedDate not supplied

Accurate registration of serial 3D MR brain images and its application to visualizing change in neurodegenerative disorders.

PURPOSE: To propose and assess methods that permit the accurate and robust registration of serially acquired 3D MR scans and to demonstrate their application in neurodegenerative disorders. METHOD: 3D T1-weighted brain images were obtained on two or more occasions from 10 normal subjects and 8 patients with neurodegenerative disorders (scan intervals 3-21 months). Variants of an automated registration procedure were compared according to the goodness and robustness of match in normal subjects. Consistency was measured using scan triplets. Change was visualized by "difference overlay images." RESULTS: A multiresolution method was necessary for robust registration. Significant improvements in the registering of control scans were produced with voxel size correction (p < 0.05), matching only brain voxels (p < 0.05), and sinc interpolation (p < 0.05). Fast sinc resampling was 20 times faster than an equivalent previous method. Subvoxel accuracy was demonstrated. Difference overlay images showed little cerebral change in normal subjects; in Alzheimer disease patients, characteristic patterns of brain atrophy were observed even with scan intervals as short as 3 months. CONCLUSION: This methodology permits subvoxel comparison of routinely acquired serial 3D MR brain scans. It is a sensitive method for tracking patterns and rates of neuroanatomical change.

Adult↗