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Biomedical subjects

D Galasko

Publications and source records attributed to D Galasko.

At least 91 records · Page 5Linked to original sources
PubMed1994

Selective rubella vaccination programmes: a survey of districts in England and Wales.

A survey of district immunisation coordinators in the 183 health districts of England and Wales was carried out to assess the implementation of selective rubella vaccination programmes. The survey showed that school health services vaccinate schoolgirls against rubella in 161 (93%) of the 173 districts whose immunisation coordinators responded. The accuracy of data on vaccination coverage of schoolgirls is limited because districts interpret the numerator and denominator required by the Department of Health in different ways. Districts have also experienced problems in monitoring the uptake of vaccination through general practitioners. Comprehensive antenatal screening programmes for rubella immunity operate in 164 districts (95%), but few districts are auditing the postpartum vaccination of seronegative women. If child health computer records were maintained and updated until children left school, it would be possible to produce reliable data on the percentage of girls who had been vaccinated against rubella by the age of 14.

Adolescent↗
PubMed1994

Clinical-neuropathological correlations in Alzheimer's disease and related dementias.

OBJECTIVE: To compare neurologists' initial clinical diagnoses made according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition guidelines with neuropathological diagnoses of Alzheimer's disease (AD) and related dementias. DESIGN: Consecutive autopsies in a prospective cohort study. SETTING: Community-dwelling patients with dementia referred to neurologists at an Alzheimer's Disease Research Center and satellite clinics (n = 151) and patients initially evaluated when institutionalized (n = 19). PATIENTS: Of 204 elderly patients who had an autopsy performed, 170 had received a complete dementia evaluation according to NINCDS-ADRDA guidelines. MAIN OUTCOME MEASURES: Percentage agreement between neurologists' initial clinical diagnoses and pathological findings. RESULTS: Of 137 patients clinically diagnosed as having probable or possible AD, 123 (90%) had AD neuropathological findings; this included 29 with AD accompanied by Lewy bodies, and 14 with AD and one or more infarcts. Cases of vascular and mixed dementia (AD and infarct[s]) had lower rates of agreement with pathological findings. Possible AD cases were more likely than probable AD cases to show pathological features other than AD. Clinicians predicted the presence or absence of AD pathological findings significantly better than chance. In patients with AD pathological lesions, older age of onset and male gender were significantly associated with shorter duration from disease onset to death. CONCLUSIONS: Clinicians accurately predicted AD pathological findings or their absence in most cases. Attributing other degenerative dementias to AD, misdiagnosing patients with combined AD and Lewy bodies and misjudging the vascular contribution to dementia were the major areas of inaccuracy. Formal criteria for dementia associated with non-AD lesions, Lewy bodies, and infarcts need to be developed and tested.

Aged↗
PubMed1994

The apolipoprotein E allele epsilon 4 is overrepresented in patients with the Lewy body variant of Alzheimer's disease.

We determined apolipoprotein E (ApoE) genotypes in 122 autopsied demented patients. The frequency of the ApoE epsilon 4 allele was 39.6% in Alzheimer's disease (AD), 29.0% in the Lewy body variant of AD (LBV), and 6.25% in diffuse Lewy body disease. For AD and LBV patients, the epsilon 4 frequency was significantly higher than that reported in nondemented controls (10 to 15%). Therefore, LBV and AD share ApoE epsilon 4 as a genetic risk factor, providing further evidence that these conditions overlap.

Aged↗
PubMed1993

Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide.

The accumulation in brain of senile plaques containing beta-amyloid protein (A beta) is a defining feature of Alzheimer's disease. The amyloid precursor protein (APP)4 from which A beta is derived is subject to several genetic mutations which segregate with rare familial forms of the disease, resulting in early onset of dementia and plaque formation, suggesting that APP metabolism plays a causal role in the disease. Various cell types have been shown to release a soluble form of A beta, thus allowing for the in vitro study of A beta generation. We report here evidence that a substantial portion of the APP secreted by human mixed brain cell cultures, as well as that present in cerebrospinal fluid, is of a novel form cleaved precisely at the amino terminus of A beta, suggesting that a secretory pathway is involved in A beta genesis.

Amyloid beta-Protein Precursor↗
PubMed1993

Plaque-only Alzheimer disease is usually the lewy body variant, and vice versa.

A minority of neuropathologically confirmed Alzheimer disease (AD) brains lack neocortical neurofibrillary tangles or have very few, constituting a form of "plaque-only AD." A significant percentage of clinically diagnosed AD patients are found at autopsy to have both AD and brainstem and neocortical Lewy bodies. Many of these Lewy body variants of AD (LBV) have numerous senile plaques but no neocortical neurofibrillary tangles, and so resemble plaque-only AD. In this study, we sought to determine if plaque-only AD was usually LBV, and, conversely, if LBV was usually plaque-only AD. We analyzed 147 consecutively accessioned cases of neuropathologically confirmed AD, diagnosed according to criteria from the National Institute on Aging and the Consortium to Establish a Registry for Alzheimer's Disease. Twenty-five percent of all AD cases in this series were plaque-only AD, and 75% were plaque and tangle AD. Twenty-eight percent of AD cases in this series were LBV, and 72% were pure AD. Of the plaque-only AD cases, 75% were LBV and only 25% were pure AD. Of the LBV, 66% were plaque-only AD and only 33% were plaque and tangle AD. These results indicate that most plaque-only AD is LBV, and, conversely, that most LBV is plaque-only AD.

Aged↗
PubMed1993

Clinical features distinguishing large cohorts with possible AD, probable AD, and mixed dementia.

OBJECTIVE: To determine whether clinical features and rate of cognitive and functional decline differed in cohorts of possible AD (poAD), probable AD (prAD), and mixed dementia (MIX) patients. DESIGN: Cohort study with 1-year follow-up examination, comparing three groups of subjects. SETTING: Outpatient evaluation at nine California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC). PATIENTS: There were 1701 elderly patients who presented for evaluation of memory complaints. MEASUREMENTS: Historical, physical, and neurological variables for cross-sectional comparisons and 1-year rate of change on the Mini-Mental State Examination (MMSE), Blessed Information-Memory-Concentration test (BIMC), and Blessed Dementia Scale (BDS). RESULTS: Mean initial MMSE scores for poAD (n = 279), prAD (n = 928) and MIX (n = 430) were 17.9 (+/- 7.4), 13.9 (+/- 7.5), and 15.4 (+/- 7.1). Delusions and psychosis occurred in about one-third of each group, most often in those with moderate dementia (MMSE 11-20). PoAD were distinguished from prAD by significantly more alcohol abuse, physical health problems, and focal motor or sensory findings. MIX differed from AD alone by increased prevalence of cardiovascular disease, hypertension, stroke, TIA, and exposure to general anesthesia, and by a greater frequency on exam of depressed mood, focal motor or sensory findings, and gait disorder. All groups declined by about 2.8 points on the BIMC, 2.9 points on the MMSE, and 1.8 points on the BDS, a functional scale, over 1 year. Neither extrapyramidal signs nor psychosis predicted a more rapid rate of decline. CONCLUSIONS: Various features help to distinguish poAD, prAD, and MIX in a large cohort of patients, but do not predict the rate of progression.

Aged↗
PubMed1993

Neurotransmitters in basal ganglia and cortex of Alzheimer's disease with and without Lewy bodies.

We measured the concentrations of the monoamines, their precursors, and their metabolites, and the activity of choline acetyltransferase (ChAT) in basal ganglia and cortical regions of postmortem brains from cases with histologically verified pure Alzheimer's disease (AD), AD with diffusely distributed Lewy bodies (Lewy body variant [LBV]), and normal controls. Dopamine and homovanillic acid (HVA) were severely depleted in basal ganglia of the LBV cases but were not significantly altered in pure AD cases; tyrosine hydroxylase levels in putamen were also significantly reduced in LBV but not AD cases. These reductions in basal ganglia dopamine and HVA suggest that LBV cases have a level of dopamine depletion similar to Parkinson's disease (PD). Additionally, ChAT activity in caudate and norepinephrine concentration in putamen were significantly reduced in the LBV group, which may have contributed to the absence of resting tremor and the milder presentation of parkinsonian features in this group compared with classic PD. In frontal, parietal, and temporal cortex, activity of ChAT in the LBV group was significantly reduced compared with controls and lower than in pure AD.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

The consortium to establish a registry for Alzheimer's disease (CERAD). Part IV. Rates of cognitive change in the longitudinal assessment of probable Alzheimer's disease.

Reliable information on rate of progression of cognitive impairment in probable Alzheimer's disease (AD) is important for evaluating possible beneficial effects of therapeutic agents and in planning long-term care for patients with this chronic illness. However, wide variability exists in published rates of change for psychometric measures of the dementing process, and there is need for an accurate analysis of large numbers of persons with the disorder studied over long periods. Utilizing the large, well-characterized sample of the Consortium to Establish a Registry for Alzheimer's Disease and employing a least squares regression method to adjust for different levels of impairment and periods of observation, we report rates of change on the Short Blessed Test, Mini-Mental State Examination, Blessed Dementia Scale, Clinical Dementia Rating, and other cognitive measures in 430 patients with probable AD (mean age at entry = 70.9 +/- 8.0 SD years) studied for up to 4 years. We found that rate-of-change determinations are less reliable when the observation period is 1 year or less, that dementia progression may be nonlinear when described by certain measures, and that simple change scores do not accurately characterize the rate of decline. We also found that rate of progression in AD is determined by the severity of cognitive impairment: the less severe the dementia, the slower the rate of decline.

Aged↗
PubMed1993

Repeated exposure to the Mini-Mental State Examination and the Information-Memory-Concentration Test results in a practice effect in Alzheimer's disease.

We analyzed short-term variation of Mini-Mental State Examination (MMSE) and Information-Memory-Concentration (IMC) Test scores in 39 patients with Alzheimer's disease (AD), tested four times over 6 weeks. Although analysis of variance had failed to show a significant "learning" effect or other trends, we reexamined the data using repeated measures models, with and without a learning effect. In the model without a learning effect, mean MMSE scores decreased minimally and mean IMC scores decreased by 0.84 points over 6 weeks. In the model that allowed a potential learning effect between the first and second test sessions, scores increased significantly, by 1.12 +/- 0.47 points for the MMSE and 1.04 +/- 0.43 points for the IMC Test. Patients' test scores predicted from the models had less variability than did their raw scores. The short-term practice effect, although small, should be considered in interpreting changes in scores, especially in therapeutic studies in AD.

Alzheimer Disease↗
PubMed1992

Lewy body disease.

Subsumed under the rubric of Lewy body disease are idiopathic Parkinson's disease (PD), pure diffuse Lewy body disease (DLBD), and, most commonly, combined brainstem and neocortical Lewy bodies with Alzheimer's disease (AD) pathology in a relatively early developmental stage. Clinical correlates are dementia with psychiatric and subcortical features plus mild extrapyramidal signs (EPS).

Alzheimer Disease↗
PubMed1991

Monitoring progression in Alzheimer's disease.

OBJECTIVE: To compare several clinical methods of following change in Alzheimer's disease (AD) over time. DATA SOURCES: MEDLINE search (restricted to English language); bibliographies of pertinent articles or books. STUDY SELECTION: Studies included only if aim was to follow a cohort of AD patients; diagnosis of AD used DSM-III-R or NINCDS-ADRDA guidelines; techniques or scales used for serial assessment were well-established in terms of validity and reliability. DATA EXTRACTION: All 3 authors reviewed all studies cited and reached consensus about interpretation. RESULTS: Global instruments detect long term deterioration in AD and describe distinct through possibly artificial stages. Cognitive screening tests decline at a consistent rate for groups of AD patients but show considerable variability. Scales measuring activities of daily living (ADLs) need further study to determine annual rate of change. Instrumental ADLs decline early in AD and reach a floor before cognitive screening tests. Electrophysiologic or radiographic techniques do not necessarily change over time and are not superior to clinical methods for following AD. Variability in rate of cognitive change and prognosis in AD has not been adequately explained. CONCLUSIONS: Cognitive screening tests provide useful measures of rate of change in AD for clinical and therapeutic studies. Further studies should take advantage of longer follow-up and more sophisticated statistical techniques to optimize use of these measures.

Activities of Daily Living↗
PubMed1990

Stimulated platelets release amyloid beta-protein precursor.

Human platelets can be stimulated by thrombin or ionomycin to secrete soluble truncated amyloid beta-protein precursor and particulate membrane fragments which contain C-terminal and N-terminal immunoreactive amyloid beta-protein precursor. This suggests a possible circulating source of beta-protein in serum which may play a role in the formation of amyloid deposits. The release of soluble amyloid beta-protein precursor could be involved in normal platelet physiology.

Amyloid↗
PubMed1990

The Mini-Mental State Examination in the early diagnosis of Alzheimer's disease.

The Mini-Mental State Examination (MMSE), a brief test of cognitive function, has been widely used to screen for dementia. We administered the MMSE to 74 community-dwelling patients meeting criteria for probable Alzheimer's disease (AD) and 74 age- and education-matched controls. Twenty-four patients with AD performed in the nondemented range by scoring above the recommended cutoff point of 23 of a possible 30 on the MMSE. We compared the scores for items of the MMSE in controls and subjects with AD and used logistic regression to model a shorter MMSE that retained the accuracy of the complete test. A score summing tests of recall and orientation for place had similar sensitivity to the full MMSE. Adding a verbal fluency test to the MMSE reduced the error rate by improving the accuracy of diagnosis of patients with AD scoring in the nondemented range.

Aged↗
PubMed1990

Neurological findings in Alzheimer's disease and normal aging.

To determine the potential value of abnormal neurological findings as markers of Alzheimer's disease (AD) and their relationship to the stage of AD, we compared standardized neurological examinations in 135 community-dwelling patients with AD and 91 nondemented elderly individuals. After correcting for differences in age and education between the two groups, we found that rigidity, stooped posture, graphesthesia, neglect of simultaneous tactile stimuli (face-hand test), and snout, grasp, and glabella reflexes were present significantly more often in patients with AD than in control subjects. These findings increased in prevalence in patients with AD according to the severity of dementia. However, in a multivariate logistic regression model only the grasp reflex, graphesthesia, and the face-hand test were statistically significantly associated with the degree of cognitive impairment. Although abnormal neurological findings occur regularly in AD, they are too infrequent early in the course of AD to serve as diagnostic markers. Prospective studies are needed to determine whether patients with the early onset of extrapyramidal or other findings form a distinct subgroup of AD.

Aged↗
PubMed1990

Lobar atrophy with dense-core (brain stem type) Lewy bodies in a patient with dementia.

A 62-year-old man presented with memory impairment progressing over 6 years to dementia with near mutism and was diagnosed as having Alzheimer's disease. At autopsy his brain showed lobar atrophy suggestive of Pick's disease and there were spherical intracytoplasmic neuronal inclusions in the fascia dentata, hippocampal pyramidal cell layer, and temporal cortex. Unlike Pick bodies, however, the inclusions were eosinophilic with H&E stains, non-argyrophilic, and failed to react immunohistochemically with antibodies to paired helical filaments or Alz-50. They did label with antibodies to ubiquitin, however, and electron microscopy disclosed dense-cored granular structures with thin filamentous coronas which resembled brain stem-type Lewy bodies. The substantia nigra and locus coeruleus were not affected.

Atrophy↗
PubMed1990

The Lewy body variant of Alzheimer's disease: a clinical and pathologic entity.

Thirty-six clinically diagnosed and pathologically confirmed Alzheimer's disease (AD) patients included 13 with cortical and subcortical Lewy bodies (LBs). The patients with LBs appeared to constitute a distinct neuropathologic and clinical subset of AD, the Lewy body variant (LBV). The LBV group showed gross pallor of the substantia nigra, greater neuron loss in the locus ceruleus, substantia nigra, and substantia innominata, lower neocortical ChAT levels, and fewer midfrontal tangles than did the pure AD group, along with a high incidence of medial temporal lobe spongiform vacuolization. Analysis of neuropsychological tests from 9 LBV subjects and 9 AD patients matched for age and degree of dementia revealed greater deficits in attention, fluency, and visuospatial processing in the LBV group. Similar comparisons of neurologic examinations showed a significant increase in masked facies; in addition there was an increase in essential tremor, bradykinesia, mild neck rigidity, and slowing of rapid alternating movements in the LBV group. Extremity rigidity, flexed posture, resting tremor, or other classic parkinsonian features were not characteristic of the LBV patient. In some cases, it may be possible to diagnose LBV premortem on the basis of the clinical and neuropsychological features.

Aged↗
PubMed1988

Intracranial mass lesions associated with late-onset psychosis and depression.

Tumors and other mass lesions of the brain may present with symptoms resembling psychosis or depression or with features of delusions, hallucinations, mania, or catatonia. There is an over-representation of tumors affecting the frontal lobe, temporal lobe, and diencephalon in patients with these manifestations. Neurologic symptoms and signs may be helpful in making an early diagnosis of the tumor. Patients with late-onset psychosis, unusual histories of depression, and those with focal neurologic findings associated with psychotic disorders should undergo computerized tomographic (CT) scanning to exclude a focal brain lesion.

Brain Diseases↗