Presenile Dementia Of Alzheimer Type Research Articles

Long-term survival, place of death, and death certification in clinically diagnosed pre-senile dementia in northern England. Follow-up after 8-12 years.

Information on survival and cause of death in pre-senile dementia is scarce and the organisation of services controversial. To study survival, place of death and death certification in pre-senile dementia. Patients aged 45-64 were identified from hospital and community sources in the Northern health region (1985-89) and classified as having pre-senile dementia of Alzheimer type (PDAT) or pre-senile vascular dementia (PVD) by applying an algorithm to case notes. Deaths were ascertained from the National Health Service Central Registry (NHSCR) to 31 December 1998. Survival analysis was performed using the SPSS/PC program, and expected survival calculated from life tables. Median survival time from diagnosis was 6.08 years and did not differ significantly in PDAT and PVD, or by age or gender; 19.3% of deaths occurred at home, 24.5% in nursing or residential homes and 56.3% in hospital; 72.4% of the death certificates mentioned dementia or Alzheimer's disease; 15.4% were still alive. Pre-senile dementia has a variable but usually chronic course, requiring appropriate planning and services.

Dependency and community care in presenile Alzheimer's disease.

In a study of patients with presenile dementia of Alzheimer type (PDAT), we aimed to investigate functional dependency in relation to the time since diagnosis and place of residence. Use of community and support services and the time between diagnosis and entry to permanent residential care were also studied. Interviews with 109 cases of PDAT (diagnosed before age 65) and their carers. The need for assistance in activities of daily living (ADL) was progressive with time from diagnosis. Five years after diagnosis, 57% of patients remained at home, 20% of whom required some assistance in each of six areas of ADL. The need for assistance in each ADL category was significantly greater for cases in permanent residential care than for those at home. There were no significant differences between the Mini-Mental State Examination (MMSE) scores of patients at home and those of patients in permanent care. Incontinence and the relationship of the carer to the patient were the strongest predictors of permanent residential care. Respite care had been offered in 63% of cases; 71% of these offers had been accepted. Patients with PDAT who have a living relative are cared for at home for a considerable period of time despite severe cognitive impairment and loss of independence measured by ADL. The reports of carers suggest there is scope for improvement in supportive services to meet this community need.

Brain electrical activity (quantitative EEG and bit-mapping neurocognitive CNV components), psychometrics and clinical findings in presenile subjects with initial mild cognitive decline or probable Alzheimer-type dementia.

Clinical, neuropsychological and neuropsychophysiological data (Q-EEG, ERPs and CNV/RT activity) were obtained from 24 patients who had more or less severe presenile primary cognitive decline without depression, and compared with similar data from 10 age-matched healthy volunteers (mean age, 59.4 years). All of the patients (15 M and 9 F; mean age 59.6 years) were selected according to the DSM III-R, ICD-10 and NINCDS-ADRDA criteria and underwent CT and MRI scanning, in addition to a standard clinical examination, a battery of psychometric tests, spectral EEG, and bit-mapped CNV complex and RT to S2 analyses. Twelve of the 24 patients presented an initial presenile idiopathic cognitive decline (PICD) but did not wholly fulfil the clinical and neuropsychological criteria for primary dementia or for a diagnosis of probable AD; the remaining 12 patients showed characteristic clinical signs and symptoms of a very probable early stage of presenile Alzheimer-type dementia (PAD). ANOVA, correlational and discriminant analyses of the neuropsychological test scores, and the neurophysiological and RT to S2 data revealed 22 highest-ranked between-group discriminant factors (all with a significance level of p < 0.01). The conclusive discriminant analysis retained 13 of these factors as final canonical functions, and these showed a 97% grouping accuracy (33 of the 34 subjects examined); the same percentage of correct classifications was also achieved using only the 15 best indicators in the group of CNV/RT findings. Using both of these sets of highest-ranked discriminators, all of the normal subjects and all of the PAD patients were correctly classified; only 1 PICD patient was misclassified as normal when the first group of 13 factors was used, and another PICD patient was misclassified as PAD using the second group of 15 factors. Our findings suggest that, providing they are correctly performed and interpreted, these non-invasive techniques may be an important tool for identifying incipient stages of presenile Alzheimer-type dementia.

Clinical and analytical considerations in the utilization of cholinesterase measurements

Many theories have been advanced but the true physiological function for serum cholinesterase has still not been identified. Evidence has been presented for the abnormal expression of cholinesterase genes in many types of human tumors. Cholinesterase measurements are still used to monitor exposure to organophosphate insecticides and their clinical application requires a good understanding of the inter and intea-individual variation, as well as some knowledge of the time sequence between exposure and measurement of the cholinesterase activity. The use of serum cholinesterase measurement in liver disease varies in different countries. A case has not been made for the cost-effectiveness of adding serum cholinesterase as part of a screening procedure for the diagnosis of liver disease. During the last 10 years much information has been obtained on the molecular biology and genetics of acetylcholinesterase and butyrylcholinesterase, distinct enzymes encoded by two different, but related genes. It has been established that BChE is included by a single gene which corresponds to the El locus. The complete amino acid sequence of human serum cholinesterase and the location of disulfide bonds within the sequence have been described. The molecular basis of many variants of human serum cholinesterase has been described in detail. It is not rare for multiple mutations to occur within a single butyrylcholinesterase gene or there may be combination of mutations. At least 11 silent variants of human butyrylcholinesterase have been identified. There still exists a wide variety of substrates and analytical conditions for butyrylcholinesterase measurement in a number of clinical situations. No real evidence has been provided for clinical value for their use in the diagnosis of Alzheimer disease or monitoring the use of cholinesterase inhibitors in the treatment of pre-senile dementia of Alzheimer type. However, the insights from molecular biology technology may well open up more challenges in a variety of clinical situations.

Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type

The effect of age on regional cerebral metabolic rate of glucose (rCMRG1) was studied in 14 patients with presenile dementia of Alzheimer type (DAT) and 24 patients suffering from senile DAT in comparison to 20 age-matched normal subjects by positron emission tomography (PET) of 2-( 18F)-fluoro-2-deoxy-D-glucose (FDG). The metabolic pattern was condensed to a single metabolic ratio. It was calculated as the quotient of rCMRG1 in regions typically affected by AD (frontal and temporoparietal cortex) divided by that in regions typically not affected. In normals this ratio was 1.05±0.04 and did not depend on age. In patients, the metabolic ratio was generally smaller and there was a significant difference between presenile (0.82±0.1) and senile DAT (0.90±0.1). This was due to a different metabolic pattern in the two age groups: metabolic impairment was focused on frontal and temporo-parietal cortex in presenile DAT, whereas more global rCMRG1 reductions were present in senile DAT. The results suggest a more generalized disorder in senile dementia impairing metabolism globally in addition to the more localized changes that are typical for DAT.

Aluminium in drinking water and risk for diagnoses of presenile Alzheimer's type dementia: L.C. Neri, D. Hewitt and S.L. Rifat. St. Vincent Hospital in Ottawa and Depts of Preventive Medicine and Biostatistics and Psychiatry; University of Toronto, Toronto, Ontario, Canada

Aluminium in drinking water and risk for diagnoses of presenile Alzheimer's type dementia: L.C. Neri, D. Hewitt and S.L. Rifat. St. Vincent Hospital in Ottawa and Depts of Preventive Medicine and Biostatistics and Psychiatry; University of Toronto, Toronto, Ontario, Canada

Topographic CNV activity mapping, presenile mild primary cognitive decline and Alzheimer-type dementia

The CNV complex evoked with a standard paradigm (S1-2 sec-S2-motor response) and reaction time (RT) to the imperative signal (S2) were recorded and measured in 12 patients with initial presenile idiopathic cognitive decline (PICD), 12 with presenile Alzheimer-type dementia (PAD) and 10 healthy age-matched controls. Significant group differences were obtained for measures of some CNV components, particularly of the late pre-S2 CNV. No significant CNV activity, very prolonged RTs and sometimes characteristic post-imperative negative variations (PINV) were observed in the majority of patients with PAD. These results suggest that similar CNV complex and RT changes to those observed in our patients may constitute a valuable clue in the study of pathophysiological brain functioning in the early stages of presenile idiopathic mental deterioration.

Cognitive event-related potentials and reaction time in presenile subjects with initial mild cognitive decline or probable Alzheimer-type dementia

The so-called contingent negative variation (CNV) is a slow brain potential representing a complex of variously overlapped "endogenous" components of behavior related to different reasonably well-known neurocognitive processes. CNV complex evoked with a standard paradigm (S1-2 sec-S2-motor response) and reaction time (RT) to imperative signal (S2) were recorded and measured in 11 patients with initial presenile idiopathic cognitive decline (PICD), 8 with presenile Alzheimer-type dementia (PAD) and 10 healthy age-matched controls. Significant group differences were obtained for measures of some CNV components, particularly of the late pre-S2 CNV. No significant CNV activity, very prolonged RTs and sometimes characteristic post-imperative negative variation (PINV) were observed in the majority of patients with PAD. These results suggest that CNV complex and RT changes similar to those observed in our patients may constitute a valuable clue for the study of pathophysiological brain functioning in the early stages of presenile idiopathic mental deterioration.

N-terminal ACTH fragments increase the CSF beta-EP content in Alzheimer type dementia.

Eleven patients with presenile Alzheimer type dementia (ATD) were treated with N-terminal ACTH fragments for 14 days. No change in cognitive functions was observed during the treatment. A significant increase in CSF beta-endorphin (beta-EP) levels was found, while ACTH and beta-lipoprotein remain unaffected. The possibility that ACTH and its moieties could interfere with beta-EP activities in CNS is discussed.

36. Event-related potentials (contingent negative variation complex) in patients with initial idiopathic presenile cognitive decline and presenile Alzheimer-type dementia

36. Event-related potentials (contingent negative variation complex) in patients with initial idiopathic presenile cognitive decline and presenile Alzheimer-type dementia

High-molecular-weight forms of somatostatin are reduced in Alzheimer's disease and Down's syndrome

Four molecular forms of somatostatin-like immunoreactivity (SOM-LI) are present in the human temporal cortex: SOM-14, SOM-28 and high-molecular-weight forms (HMW-SOM) of 7500 and 12,000 daltons. SOM-14 and HMW-SOM are depleted in cortical tissue from cases of pre-senile Alzheimer-type dementia (ATD), but there is a disproportionate reduction in HMW-SOM. In cases of Down's syndrome (DS) with the neuropathological and neurochemical changes of ATD, the total concentration of SOM-LI was similar to that in control cases and the proportions of molecular forms present were comparable. However, there was a significant reduction in the concentration of HMW-SOM. These results show that ATD and DS may share a common abnormality in the biosynthesis and/or post-translational processing of cortical SOM.

Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and down's syndrome

Noradrenaline, dopamine, homovanillic acid (HVA), choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) levels were measured in post-mortem brains from 8 cases of pre-senile Alzheimer-type dementia (ATD), 5 cases of senile ATD, 4 cases of Down's syndrome aged 53–57 years, one 27-year-old case of Down's syndrome and 13 controls. In the controls, the concentration of noradrenaline in hypothalamus ( P < 0.05) and mamillary body ( P < 0.02) decreased with age. Compared with age-matched controls, noradrenaline levels in these areas were more markedly reduced in pre-senile ATD ( P < 0.01), the 53–57-year-old cases of Down's syndrome ( P < 0.001) and in the 27-year-old Down's, than in senile ATD (hypothalamus P < 0.05, mamillary body, n.s.). Dopamine and HVA concentrations in caudate nucleus were unaltered in pre-senile or senile ATD but dopamine was decreased ( P < 0.01) in the older cases, although not in the 27-year-old case, of Down's syndrome. In the olfactory tubercle in ATD the level of HVA was unal tered but the activity of ChAT was decreased ( P < 0.01). ChAT activity was reduced in pre-senile ATD ( P < 0.001), the older Down's cases ( P < 0.01) but not the young Down's case, and senile ATD ( P < 0.001) in the temporal cortex and in pre-senile ATD ( P < 0.001) and the older Down's cases ( P < 0.001) but not senile ATD in the caudate nucleus. AChE activity was reduced in the temporal cortex and caudate nucleus in pre-senile ATD ( P < 0.001andP < 0.05, respectively) and Down's syndrome ( P < 0.00) but in only the temporal cortex ( P < 0.05) in senile ATD. The results suggest that there is a greater loss of noradrenergic and cholinergic neurons in pre-senile ATD and Down's syndrome than in senile ATD and that dopamine neurons are unaffected in ATD although altered in activity in cases of Down's syndrome with the clinical and neuropathological characteristics of ATD.

Alzheimer's disease in one monozygotic twin.

A woman of 64 died after an illness lasting 15 years and characterized by a progressive amnesic syndrome followed by global dementia. The brain showed changes typical of Alzheimer's disease. Her monozygotic twin sister was clinically not affected and died two years later of carcinoma. This is the second report of monozygotic twin sisters apparently discordant for presenile dementia of Alzheimer type.