Vascular dementia: a contemporary review of epidemiology, diagnosis, prevention, and treatment

The past decade has seen a renewed interest in vascular dementia. Key epidemiologic studies have examined the prevalence, incidence, course and risk factors of vascular dementia. New classification systems have been developed to improve the reliability of the diagnosis, and there have been advances in diagnostic methodology, such as neuroimaging and neuropsychological assessment. New treatments for vascular dementia are being developed to protect the brain from cerebral ischemia and to limit progression of cognitive impairment. Diagnostic criteria for vascular dementia remain to be validated by carefully designed, systematic, clinicopathologic study. Once such criteria are validated, meaningful study of subgroups of vascular dementia can be explored. Until the relationship between vascular dementia and Alzheimer's disease is better defined, the nosology for vascular dementia may be defined best as dementia associated with stroke.     

Tumor necrosis factor inhibits the transcriptional rate of glucose-6-phosphatase in vivo and in vitro

OBJECTIVE: After Alzheimer's disease, vascular dementia (VaD) and frontotemporal dementia (FTD) are among the most common dementing illnesses. FTD may have a neuropsychological profile similar to that of VaD, and patients with these dementias may be difficult to distinguish on clinical examination. The purpose of this study was to elucidate distinct cognitive profiles of a large group of FTD and VaD patients on a brief, clinical mental status examination. DESIGN: A comparison of 39 FTD patients and 39 VaD patients on a brief, clinical mental status examination. SETTING: A Dementia Research Center and affiliated, university hospitals. METHODS: The FTD patients were diagnosed by noncognitive clinical and neuroimaging criteria, and the VaD patients met NINDS-AIREN criteria for vascular dementia. The two dementia groups were comparable on three dementia assessment scales. MEASUREMENTS: The mental status measures included the neuropsychological battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), plus supplementation from the Neurobehavioral Cognitive Status Examination (NCSE) for cognitive areas not assessed by the CERAD). RESULTS: The FTD and VaD groups differed significantly on the mental status examination measures. FTD patients performed significantly better than the VaD patients on digit span and constructions, despite comparable performance by both groups on calculations. Although not statistically significant, the FTD group performed worse than the VaD group on verbal fluency and abstractions. These differences were not explained by group differences in age and education. CONCLUSION: These results suggest that cognitive differences between FTD and VaD groups reflect greater frontal pathology in contrast to relative sparing of posterior cortex and subcortical white matter in FTD. These cognitive differences as measured by a mental status examination may help distinguish between these two dementia syndromes.     

Cognitive loss in dementia with Lewy bodies and Alzheimer disease

BACKGROUND: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. Some preliminary evidence exists that the pattern of cognitive impairment in DLB is different from that in Alzheimer disease (AD). OBJECTIVE: To delineate features of cognitive impairment of DLB on standardized neuropsychological tests. METHODS: We performed neuropsychological assessments of 26 patients with probable DLB (based on criteria of the consortium on DLB international workshop) and of 52 patients with probable AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke [now the National Institute of Neurological Disorders and Stroke])-Alzheimer's Disease and Related Disorders Association) who were matched to the patients with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. RESULTS: Compared with the group with probable AD, the group with probable DLB scored significantly lower on the picture arrangement, block design, object assembly, and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised and on the Raven Colored Progressive Matrices test and significantly higher on the Mini-Mental State Examination locational orientation subtest and the Alzheimer's Disease Assessment Scale word recall subtest. A discriminant analysis revealed that the word recall score on the Alzheimer's Disease Assessment Scale and the block design score on the Wechsler Adult Intelligence Scale-Revised were the best discriminant factors. CONCLUSIONS: The disproportionately severe visuoperceptual, visuoconstructive, and visuospatial dysfunction and the disproportionately mild memory impairment in DLB compared with AD, which likely reflect the distribution of the pathologic changes in DLB, can help to differentiate DLB from AD.     

Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Japanese patients

OBJECTIVE: To look for preclinical markers of Alzheimer's dementia in a sample of healthy, oldest old individuals. DESIGN: Prospective, longitudinal study of individuals examined at yearly intervals with neuropsychological tests selected to be sensitive to the early detection of dementia. PARTICIPANTS: One hundred and thirty-nine community-dwelling, functionally independent, healthy individuals 65 to 106 years of age who met strict criteria for lack of dementia at entry. Incident dementia cases consisted of 16 volunteers all 80 years old or older who developed dementia of the Alzheimer's type and 31 volunteers 80 years old and older showing no evidence of dementia during a mean 2.8-year follow-up interval. MEASUREMENTS: Scores on 10 neuropsychological measures were analyzed for the initial examination when none of the volunteers showed clinical evidence of dementia and for the two subsequent yearly examinations. RESULTS: Individuals who subsequently developed dementia showed evidence of verbal memory impairment at their initial examination, which was a mean of 2.8 years before clinical evidence of dementia. The average yearly incidence rate for dementia in those 80 years of age and older was 12%. Performance of individuals who did not development dementia remained relatively stable during follow-up for up to 5 years. CONCLUSION: Alzheimer's disease has a preclinical stage in which verbal memory decline is the earliest sign. Dementia in the oldest old is distinguishable from age-related cognitive decline.     

Comparative evolution of Alzheimer disease, vascular dementia, and mixed dementia

OBJECTIVE: To compare the evolution of Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia by cognitive domain. SETTING: The University of Western Ontario Dementia Study, which is a registry of cases of dementia seen for secondary and tertiary assessment in a university memory disorders clinica with extensive follow-up data and histopathological confirmation of clinical diagnoses. PATIENTS: One hundred twenty-nine patients with definite or probable AD, 12 patients with definite or probable VaD, and 36 patients with definite or probable mixed dementia. METHODS: Patients were grouped as having an early, moderate, or advanced stage of disease according to the extended scale for dementia (ESD). The ESD was subdivided into cognitive domains, and the domain scores were compared for each stage of disease by diagnostic category with the use of a 2-way analysis of variance with repeated measures. RESULTS: As expected, the scores in all domains decreased significantly with increasing severity. There was a significant difference in the decline in memory among the diagnostic groups (P = .02) that was mostly attributable to the difference between AD and mixed dementia (P = .03), with the difference between AD and VaD only approaching significance (P = .06). There was a similar finding for praxis. The interaction between diagnosis (AD and VaD) and severity was significant only for memory (P = .02), showing a less severe memory deficit at onset but a proportionately more rapid progression in VaD and arithmetic ability (AD and mixed dementia [P = .03]). CONCLUSIONS: Alzheimer disease, VaD, and mixed dementia evolve similarly as assessed using cognitive domains obtained by subdivision of the ESD in a patient population derived from a memory clinic and by analyzing VaD as a single entity. Only memory impairment evolves differently between AD and VaD, with this depending on the severity. Memory is more severely impaired in the early stage of AD; however, with increasing severity of dementia, memory impairment in VaD accelerates and catches up with AD at the level of moderate impairment. The differences between AD and mixed dementia are greater than those between mixed dementia and VaD, suggesting an important role for the ischemic component of mixed dementia. Simple neuropsychological tools (eg, the ESD) may be incapable of distinguishing between AD and VaD, and more focused instruments may be required. Inherent bias in case selection may prevent extrapolation of these results to VaD in general, but the neuropsychological criteria for VaD may need to vary, depending on the severity.     

Neuropathologic diagnostic outcomes from a cohort of outpatients with suspected dementia

BACKGROUND: Researchers, clinicians, patients, and families need to know the accuracy of clinical dementia diagnoses. METHODS: A prospective cohort of outpatients presenting with complaints of cognitive impairment to a geriatric clinic was established from 1978 to 1982. All patients initially received a standardized clinical evaluation and then were followed longitudinally. RESULTS: Of 304 patients originally enrolled, 72 have come to autopsy and neuropathologic evaluation. Of those patients, 56 had been clinically diagnosed with Alzheimer's disease (AD) and 16 had been diagnosed with other conditions. The sensitivity, specificity, and diagnostic accuracy of the clinical diagnosis of AD compared with neuropathologic diagnosis was 95%, 81%, and 92%, respectively. CONCLUSION: Our findings support the conclusion that the practicing clinician using standardized clinical criteria can accurately diagnose AD approximately 90% of the time. These data may also be useful in the planning of future care of the AD patient.     

Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia

OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia. METHODS: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinson's disease with dementia had a significantly higher prevalence of major depression than patients with Alzheimer's disease; patients with Alzheimer's disease showed more severe anosognosia and disinhibition than patients with Parkinson's disease. Whereas no significant between group differences were found on tests of memory and language, demented patients with Parkinson's disease had a significantly greater impairment on a test of visual reasoning than patients with Alzheimer's disease. CONCLUSION: There were significant psychiatric differences between patients with Alzheimer's disease and demented patients with Parkinson's disease, but neuropsychological differences were restricted to a single cognitive domain.     

Recent advances in skeletal-muscle-based gene therapy

OBJECTIVE: To determine the sensitivity and specificity of postmortem dementia diagnoses based on a retrospective informant interview by comparison with criterion standard neuropathological diagnoses and the results of previous clinical examinations. SETTING: Three university-based academic research centers. SUBJECTS: Fifty-four deceased elderly persons with Alzheimer disease, another dementing disorder, a neurologic disease resulting in functional impairment but no dementia, or no neurologic disorder. METHODS: Blinded nonclinician interviewers administered the Dementia Questionnaire (DQ) by telephone to informants, typically close relatives, who were familiar with the intellectual and functional status of the subjects before death. Two senior clinicians (LJ.T. and C.K.) rated each DQ for the presence or absence of a dementia syndrome during life and for the specific disorders causing the dementia, if present. Raters were blinded to the neuropathological findings and based their assessments only on data provided by responses to the DQ. Comparison was made with diagnoses based on neuropathological assessment. In most cases, the results of antemortem clinical examinations were also available as a check on the clinical diagnosis of the dementia syndrome. Sensitivity and specificity of the DQ diagnoses were computed, and chance-corrected agreement measures were calculated for the 2 independent DQ raters (LJ.T. and C.K.). RESULTS: Compared with antemortem clinical diagnosis, the average sensitivity of the DQ for the clinical syndrome of dementia was 92.8%, the specificity was 89.5%, and the interrater agreement was 98% (kappa = 0.96). Among 7 subjects with mild dementia (Mini-Mental State Examination score > or = 24 at the last clinical examination), 5 (71%) were correctly identified using the DQ. The DQ correctly indicated the absence of dementia in 8 (80%) of 10 subjects with other neurologic disorders causing functional impairment. Compared with the neuropathological diagnoses, the DQ differentiated Alzheimer disease from other primary causes of dementia with a sensitivity of 89% and a specificity of 72%. The interrater agreement was 93.8% (kappa = 0.85). CONCLUSIONS: Compared with the results of the antemortem clinical examinations, the DQ was sensitive to the presence of dementia, detected most cases of mild dementia, and discriminated dementia from other neurologic disorders causing functional impairment. Compared with the neuropathological diagnoses, the ability of the DQ to differentiate Alzheimer disease from other dementing disorders indicates that it may be useful as a research tool.     

Does sub-lethal exposure to organophosphate pesticide affect capture rates in free-living rodents?

Patients with clinical diagnoses of Alzheimer's disease, vascular dementia, or undifferentiated dementia were rated on standardized measures of depression, cognitive impairment, and functional impairment. Logistic regression was used to evaluate the relationship between functional or cognitive impairment, as well as their interaction, and depressive features in each group. This analysis revealed notable differences by type of dementia. The results imply that the mechanisms underlying depression in Alzheimer's disease may be different from those in vascular and other types of dementia. These results also provide indicators to the clinician for further evaluation of depression in different dementia subtypes.     

The Mental Deterioration Battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The Group for the Standardization of the Mental Deterioration Battery

This study aimed at investigating the clinical usefulness of the Mental Deterioration Battery (MDB) in the neuropsychological diagnosis and characterization of the dementia syndrome. In this paper, we report: (a) normative data for various test scores derived from the analysis of performance of 340 normal subjects living in urban areas; (b) an evaluation of the reliability of the single tests and of the battery as a whole in differentiating normal subjects from patients affected by cognitive deterioration derived from the analysis of performance of 130 normal subjects living in rural areas and 134 patients affected by probable Alzheimer's dementia; (c) a cluster analysis of performances of the 340 normal subjects in the standardization group to evaluate possible criteria of homogeneity according to which the various MDB scores tend to aggregate; (d) an analysis of performance profiles of 183 patients with right monohemispheric focal lesions, 159 patients with left unilateral lesions with aphasia and 131 left-lesioned nonaphasic patients to evaluate the specificity of the single tests of the battery in documenting a selective impairment of one of the two cerebral hemispheres. Results confirm the reliability of the MBD in discriminating between normal and demented patients and provide indications for use of the battery in differentiating qualitative patterns of cognitive impairment.     

Alzheimer's disease and its Lewy body variant: a clinical analysis of postmortem verified cases

OBJECTIVE: The authors compared clinical findings of Alzheimer's disease and the so-called Lewy body variant of Alzheimer's disease. METHOD: Available data were analyzed on the clinical features of 58 patients with Alzheimer's disease and 24 patients with the Lewy body variant of Alzheimer's disease who underwent postmortem examination. RESULTS: The proportion of men was significantly larger in the Lewy body variant group than in the Alzheimer's disease group (66.7% versus 34.5%), and, concordantly, the Lewy body variant group was slightly taller. The prevalence of hallucinations and delusions was significantly higher in Lewy body variant subjects than the Alzheimer's disease subjects, but there were no significant differences between the two groups in educational attainment, family history of dementia, age at onset, duration of illness, cognitive impairment, overall severity of illness, or neuropsychological findings. Patients with the Lewy body variant of Alzheimer's disease tended to experience more frequent extrapyramidal side effects of neuroleptics than did the patients with Alzheimer's disease, but for patients in the two groups who were not exposed to neuroleptics, there was little difference in frequency of extrapyramidal side effects. CSF concentration of homovanillic acid (HVA) was significantly lower in the Lewy body variant patients, even when correction was made for height. CONCLUSIONS: The Lewy body variant of Alzheimer's disease may be suspected in elderly male dementia patients who otherwise meet criteria for Alzheimer's disease but who manifest significant psychiatric symptoms and neuroleptic-induced extrapy-ramidal side effects and have low levels of CSF HVA.     

Comparison of psychodiagnostic methods for dementia and deterioration

Several cognitive impairment/dementia diagnostic methods were examined concerning their results: (a) in the differentiation of accidental and pathological ability changes; (b) in the demonstration/exclusion of cognitive impairment; and (c) the degree of dementia. Sixty-five patients suffering from brain damage were examined with five accepted methods of diagnosing dementia (Syndrom-kurztest, KAI-MWT-Methode, Demenz-Test, Mini-Mental-Status-Test, Wurzer-Methode) and a comprehensive performance test battery as an external criterion for valid determination of the degree of dementia and definite differentiation of accidental and pathological performance changes. The five methods of diagnosing dementia differ appreciably in determining the degree of severity (r = 0.44). They are effective in registering accidental performance changes in comparison with the outer criterion, but pathological changes are inaccurately registered (hit rate 88%/53%); the results concerning the degree of cognitive impairment are identical: between 25 and 43% (r = 0.43). High rates (58%) of false-negative diagnoses are especially apparent in the range of slight and intermediate cognitive impairment. The methods examined are only useful for the demonstration and not for the exclusion of severe cognitive impairment (dementia) and in no circumstances for the registration of slight/intermediate cognitive impairment. Valid diagnosis of cognitive impairment/dementia necessitates the use of test batteries that differentiate functions including the premorbid performance level.     

Unraveling the mystery of cognitive changes in old age: correlation of neuropsychological evaluation with neuropathological findings in the extreme old

In order to understand what cognitive changes can be expected with aging versus those caused by disease, the New England Centenarian Study examined correlations between neuropsychological evaluation and neuropathological studies of centenarian subjects. Sixty-nine subjects were administered an extensive neuropsychological test battery designed for centenarians. Six brain donors from this group have subsequently died, and neuropathological studies of their brains have been performed to determine the presence of Alzheimer's disease (AD) and other pathological states. Of these six centenarians, three subjects had Clinical Dementia Rating scores of 0 and no dementia on neuropsychological testing, and subsequent neuropathology showed very limited AD changes. In fact, despite a range of neuropsychological findings, none of the subjects in this series met neuropathological criteria for a diagnosis of definite AD. Findings suggest that dementia is not inevitable with aging and that dementia in this age group is surprisingly often not attributable to AD.     

Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease

BACKGROUND: The epsilon4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. METHODS: We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE epsilon4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard. The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to generate receiver-operating-characteristic curves plotting sensitivity against the false positive rate. RESULTS: Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and the diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of those with pathologically confirmed Alzheimer's disease, had at least one APOE epsilon4 allele. The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and specificity of the APOE epsilon4 allele were 65 and 68 percent, respectively. The addition of information about the APOE genotype increased the overall specificity to 84 percent in patients who met the clinical criteria for Alzheimer's disease, although the sensitivity decreased. The improvement in specificity remained statistically significant in the multivariate analysis after adjustment for differences in age, clinical diagnosis, sex, and center. CONCLUSIONS: APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test for Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis.     

Preserved cognitive skills in dementia of the Alzheimer type

OBJECTIVE: To describe preserved cognitive skills in patients with dementia. DESIGN: Case series. SETTING: Community clinic. PATIENTS: Five patients who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease and were claimed to retain a cognitive skill. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Standard neuropsychological tests and individualized measures of patient's skilled behaviors. For patients who remained skilled at games, performance was compared with that of normal controls in direct competition. For the patient-trombonist, raters compared premorbid and postmorbid recordings of his play. RESULTS: One patient continued to play the trombone in a Dixieland band, although he could not name well-known numbers that he played. Another continued to solve adult jigsaw puzzles. A third patient retained skill at canasta, the fourth at dominoes. The fifth patient remained a skillful contract bridge player, although he could not name the suits or articulate simple bidding rules. Four patients had impaired performance on standard anterograde and remote memory and naming tests but performed normally on pursuit rotor and letter fluency tests. Mini-Mental State Examination scores for these patients ranged from 10 to 22. One patient refused neuropsychological testing but displayed his skill. CONCLUSIONS: Together with previous studies of preserved piano playing or painting skills, our findings indicate that a broad range of complex cognitive abilities may be preserved in patients with dementia of the Alzheimer type who cannot perform simpler actions.     

Heterogeneity of cognitive profiles in dementias of the Alzheimer type: theoretical aspects and clinical consequences

Presently, Alzheimer's disease can only be diagnosed with the coexistence of clinical symptoms and the presence of neuropathological alterations. Thus, in the absence of pre mortem biological markers, cognitive deficits form the starting point and the basis of inclusion criteria on which the clinician relies in order to make a putative diagnose of dementia of the Alzheimer type (DTA). Cognitive deficits should thus be accurately described through neuropsychological testing since it is essential to identify the cognitive deterioration patterns of the patients--in terms of selective impairment of cognitive functions--as well as the evolution of these patterns. Regarding this issue, the classical teaching of the Geneva school has proposed a homogeneous deterioration of the aphasic-apraxicagnosic syndrome into four stages. However, recent work does not support this hypothesis. On the contrary, these studies tend to show the presence of heterogeneity in neuropsychological manifestations of the disease. The aim of the present paper is to provide a critical review of this topic through a brief survey of the classical work and research that have recently been conducted. An analysis of the possible candidates responsible for the existence of this heterogeneity of cognitive profiles is presented. Finally, theoretical implications and clinical repercussions are discussed.     

Interobserver variability in the diagnosis of high-grade prostatic intraepithelial neoplasia and adenocarcinoma

High-grade prostatic intraepithelial neoplasia (PIN) is a strong predictor of carcinoma when identified in small-needle biopsy specimens. However, the diagnostic variability of PIN is unknown. Eight pathologists reviewed 321 prostatic biopsy specimens to assess the variability of the diagnosis of high-grade PIN and carcinoma. All of the specimens were classified as negative, high-grade PIN, suspicious for high-grade PIN, carcinoma, or suspicious for carcinoma, more than one diagnosis was permitted, except for negative. We compared diagnoses made by two observers by pairing them for negative versus high-grade PIN, negative versus carcinoma, high-grade PIN versus carcinoma, and all diagnostic categories together. Mean kappa coefficient values for 28 interobserver combinations were 0.451, 0.845, 0.669, and 0.482, respectively, for each of the four comparison combinations considered. Our results indicate a high level of agreement, "almost perfect" (kappa = 0.81-1.0) for carcinoma, "moderate" (kappa = 0.41-0.60) for high-grade PIN, and "substantial" (kappa = 0.61-0.81) for high-grade PIN versus carcinoma. We found that variability was related to the level of interest in prostatic pathology, the conditions of the study, the subjective application of diagnostic criteria, and the influence of peers and clinical colleagues.     

Overview of clinical trials of hydergine in dementia

OBJECTIVE: To assess the overall effect of Hydergine (a combination drug called ergoloid mesylates) on patients with possible dementia and to investigate potential moderators of an effect. DATA SOURCES: MEDLINE, EMBASE, and two proprietary databases were searched for reports of clinical trials. STUDY SELECTION: Included were randomized, placebo-controlled, double-blind, parallel-group trials in subjects with symptoms consistent with dementia performed with specified outcome instruments and sufficient statistical information to calculate effect sizes. Forty-seven (31%) of 151 trials reviewed met selection criteria. DATA EXTRACTION: Potential moderating variables were extracted from each trial: sample size, inpatient-outpatient status, trial duration, age, gender, medication dose, publication year, and diagnostic grouping. Outcome measures were extracted with their associated statistics. DATA SYNTHESIS: The overall combined treatment effects ("adjusted d") for three types of outcome measures were calculated. Overall, Hydergine was more effective than placebo as assessed by comprehensive ratings (d = 0.47; 95% confidence interval [CI], 0.38 to 0.56; P = .0001), clinical global ratings (d = 0.56; 95% CI, 0.44 to 0.68; P = .0001), and combined neuropsychological measures (d = 0.27; 95% CI, 0.22 to 0.32; P = .0001). Inpatient status, daily doses of 4 mg or more, and vascular dementia were generally associated with larger effects. The effect in patients with possible Alzheimer's dementia was significant only for combined neuropsychological measures in five trials (d = 0.30; 95% CI, 0.16 to 0.44; P = .0001; and with a dose-response, P = .001). CONCLUSIONS: Overall, ergoloid mesylates were more effective than placebo. However, the effect in patients with possible Alzheimer's dementia was very modest at best. The dose-response relation suggests that potentially effective doses may be higher than the currently approved. The circumstances of the efficacy of Hydergine remain inadequately defined.     

Alzheimer's disease in the NAS-NRC Registry of aging twin veterans, IV. Performance characteristics of a two-stage telephone screening procedure for Alzheimer's dementia

In the course of a large twin study of Alzheimer's disease we used a two-stage telephone screening procedure. The modified Telephone Interview for Cognitive Status (TICS-m) served as an initial screen for dementia in 12709 individuals. The telephone Dementia Questionnaire (DQ) was then asked of collateral informants for subjects with TICS-m scores below 28, as well as for samples of persons with higher TICS-m scores. Based upon DQ responses, individuals with cognitive impairment not attributable to focal causes underwent assessment for the clinical diagnosis of Alzheimer's disease ('Alzheimer's dementia'), as did their twins. Well-defined Alzheimer's dementia was apparent in 39 subjects. Employing a cut-off of 27 or lower as indicative of cognitive impairment, the sensitivity of the TICS-m in the detection of Alzheimer's dementia was estimated at > 99% and specificity at 86%. Inclusion of the DQ increased the specificity at the 27/28 cut-point to 99%. The TICS-m score was associated with an area under the receiver operating characteristic (ROC) curve of 0.88 (95% confidence interval 0.81 to 0.94). The maximum number of cases of Alzheimer's dementia remaining undetected in the sample was estimated to be 34.