Dementia in the adult U.S. population is a devastating disorder that is often unrecognized or misdiagnosed in its early stages. Despite the current lack of unequivocally effective treatment, recognition of early-stage dementia may offer substantial benefits. These include avoidance of inappropriate treatment related to misdiagnosis and time for the patient and family to address issues of financial, legal, and medical care planning. This Clinical Practice Guideline is intended to help primary care providers recognize and assess Alzheimer's disease and related dementias in their early stages. Differential diagnosis is beyond the scope of the guideline; however, the guideline contains a list of resources for further clinical evaluation once probable dementia has been identified. Guideline recommendations focus on the following areas: Triggers that should prompt a clinician to undertake an assessment for early-stage dementia. The components of an initial assessment, including tests of mental status and functional performance. A flow chart for early recognition and initial assessment, including assessment for delirium and depression. Interpretation of test results and appropriate actions. The role of neuropsychological testing. Knowledge of the individual patient is emphasized, including change in ability from baseline, as is the value of reliable informant reports to initial assessment and clinical judgment. This guideline should help clinicians recognize symptoms of possible dementia and decrease underrecognition and misdiagnosis of this devastating condition. This document is in the public domain and may be used and reprinted without special permission, except for those copyrighted materials noted for which further reproduction is prohibited without the specific permission of copyright holders. AHCPR appreciates citation as to source, and the suggested format is provided below: Costa PT Jr, Williams TF, Somerfield M, et al. Recognition and Initial Assessment of Alzheimer's Disease and Related Dementias. Clinical Practice Guideline No. 19. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research. AHCPR Publication No. 97-0702. November 1996.

There is concern that life is curtailed when patients with Alzheimer's disease (AD) are institutionalized. To determine whether placement in a nursing home reduces their remaining years of life, we examined the experience of White patients with AD (n = 890) enrolled in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Proportional hazards survival analysis using the landmark approach (with the landmark set to 12 months after CERAD entry and reevaluated at succeeding 6-month time intervals through 5 years) indicated that longevity at home and in the nursing home was comparable. Thus, in these patients enrolled at tertiary care medical centers, living at home or in a nursing home did not affect time to death. These data suggest that when home care is no longer feasible, families and nurses counseling them should not feel that they are curtailing life by placing an AD patient in a nursing home.

Norms for cognitive measures used to assess dementia are scant for minority groups, in particular for older Japanese Americans. Using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychology Battery, we compared the baseline performance of demented and nondemented Japanese Americans. Participants came from two harmonized epidemiological studies of dementia which were examined separately: the Kame Project, Seattle (350 men and women; 201 nondemented), age 65 and older; Honolulu-Asia Aging Study (HAAS), Hawaii (418 men; 120 nondemented), age 71 and older. The measures examined were Verbal Fluency; abbreviated Boston Naming; constructional praxis; and Word List Learning, Recall, and Recognition. Within each study, the CERAD measures distinguished between nondemented participants and those with mild cognitive impairment. Among persons with dementia, average level of performance decreased as severity of dementia increased. Determinants of score (age, education, language of administration, stage of dementia) varied between the two studies. Among Japanese Americans, the CERAD Neuropsychology Battery distinguished nondemented persons from those with dementia, but was less consistent in distinguishing levels of severity of dementia. This battery is useful for comparative epidemiological studies of dementia in minority populations. (JINS, 2005, 11, 192–201.)

Non-invasive ultrasonic imaging of the carotid bifurcation by duplex scanning and ultrasonic arteriography combined with pulsed Doppler spectrum analysis demonstrated patency of the external and internal carotid arteries distal to a common carotid occlusion in 3 patients. Common carotid occlusion is not invariably associated with thrombosis of the ipsilateral internal carotid artery. Identification of internal carotid patency by the use of ultrasonic techniques will permit surgical treatment in selected cases. Stroke, Vol 11, No 3, 1980

INADEQUATE PERFUSION of the brain in vascular disease produces a reduction in the cellular concentration of essential substrates. As a result, neuronal function is disturbed and a neurologic deficit develops. Hypoxia appears to be the most critical of the many factors influencing adequacy of perfusion and survival of ischemic tissues; therefore, an increase in delivery of oxygen to ischemic tissue should be of therapeutic value.1 Unfortunately, the poor solubility of oxygen prevents the usual forms of inhalation therapy from enhancing oxygen transport significantly; for example, the respiration of pure oxygen at a normal environmental pressure will increase arterial transport only 1.5 volumes per cent if hemoglobin is already normally saturated. Since the solubility of oxygen in blood is a linear function of the partial pressure, inhalation of this gas in a hyperbaric environment will increase the tension of oxygen in arterial blood proportionally to the rise in atmospheric pressure. Experimental observations in animals and normal man confirm this anticipated increase in transport of oxygen for a given blood flow during hyperbaric oxygenation.2 3 This increase in oxygen availability to tissues led to the present studies of hyperbaric therapy for patients with ischemia of the central nervous system.

The CERAD Neuropsychological Battery, includes 7 measures: Verbal Fluency; Modified Boston Naming; Mini-Mental State: Word List Learning, Recall and Recognition; Constructional Praxis. It was originally developed to evaluate patients with a clinical diagnosis of Alzheimer's disease, but is increasingly used in epidemiological studies of the incidence and prevalence of dementia in the elderly. The current study reports norms for African American and White representative community residents 71 years of age and older in North Carolina, and compares performance with that of African Americans in Indianapolis and with Whites in the Monongahela Valley, Pennsylvania. For all 3 studies, increased education and younger age was related to better performance on each of the 7 measures. Sex differences, when present, tended to favor women. Although on average African Americans performed more poorly than Whites, with demographic characteristics controlled, no significant racial differences were found in the North Carolina sample. Both African American and White participants in North Carolina performed more poorly than their racial counterparts in the other 2 studies, possibly because of selection-induced differences in health and educational status. Nevertheless, the use of an identical evaluation battery, such as the CERAD neuropsychologic instrument, facilitates comparisons not otherwise possible, and should be encouraged.

OBJECTIVE:To compare the clinical, neuropsychological, and neuropathologic findings in patients with AD alone with those in patients with the Lewy body variant of AD (LBV).BACKGROUND:Prior studies indicate that patients with LBV not only have distinct clinical and neuropsychological differences from those with AD alone, but have a poorer prognosis with shorter survival time.METHODS:The authors evaluated 74 patients with autopsy-confirmed AD alone and 27 patients with LBV, and compared demographic characteristics and clinical, neuropsychological, and neuropathologic findings.RESULTS:The two groups of patients were equivalent with respect to age at time of entry into the study, years of education, and sex. Two or more extrapyramidal clinical manifestations were found in 44% of patients with LBV, compared with 16% of patients with AD alone (p = 0.02). Duration of survival after entry into the study was similar in both groups, with a mean survival of 3.6 (+/-2.1) years for AD alone versus 3.8 (+/-1.9) years for LBV. Of the various neuropsychological tests administered at the last Consortium to Establish a Registry for Alzheimer's Disease evaluation, only delayed recall of a learned word list was significantly different in the two groups, with 32% of patients with LBV versus 15% of patients with AD alone recalling any items (p = 0.04). Neuropathologic findings confirmed those of previous studies and showed that neurofibrillary tangles were significantly less frequent in the neocortex of patients with LBV than in those with AD alone.CONCLUSION:Compared with patients with AD alone, those with LBV had a greater frequency of extrapyramidal manifestations, somewhat better recall on a selected memory task at their final evaluation, and a significantly lower frequency of neocortical neurofibrillary tangles at autopsy. There were no differences between the two groups, however, in survival time from entry into the study.

Objective: To compare the clinical, neuropsychological, and neuropathologic findings in patients with AD alone with those in patients with the Lewy body variant of AD (LBV). Background: Prior studies indicate that patients with LBV not only have distinct clinical and neuropsychological differences from those with AD alone, but have a poorer prognosis with shorter survival time. Methods: The authors evaluated 74 patients with autopsy-confirmed AD alone and 27 patients with LBV, and compared demographic characteristics and clinical, neuropsychological, and neuropathologic findings. Results: The two groups of patients were equivalent with respect to age at time of entry into the study, years of education, and sex. Two or more extrapyramidal clinical manifestations were found in 44% of patients with LBV, compared with 16% of patients with AD alone (p = 0.02). Duration of survival after entry into the study was similar in both groups, with a mean survival of 3.6 (±2.1) years for AD alone versus 3.8 (±1.9) years for LBV. Of the various neuropsychological tests administered at the last Consortium to Establish a Registry for Alzheimer’s Disease evaluation, only delayed recall of a learned word list was significantly different in the two groups, with 32% of patients with LBV versus 15% of patients with AD alone recalling any items (p = 0.04). Neuropathologic findings confirmed those of previous studies and showed that neurofibrillary tangles were significantly less frequent in the neocortex of patients with LBV than in those with AD alone. Conclusion: Compared with patients with AD alone, those with LBV had a greater frequency of extrapyramidal manifestations, somewhat better recall on a selected memory task at their final evaluation, and a significantly lower frequency of neocortical neurofibrillary tangles at autopsy. There were no differences between the two groups, however, in survival time from entry into the study.

Reply from the Authors: We were pleased to learn that Professor Jellinger found that CERAD neuropathology criteria for Alzheimer's disease (AD) significantly correlated with Mini-Mental Status …

Concerns about intercenter variation in methods and interpretation prompted CERAD investigators to examine standardization of the neuropathological assessment of Alzheimer's disease (AD). Contiguous frontal lobe sections derived from autopsy brains of eight patients clinically diagnosed as having probable AD and two cognitively normal individuals were distributed to 24 neuropathologists from 18 medical centers in the United States and Canada. Using their routine staining method(s), neuropathologists determined the rank order of severity of AD neuropathology in these cases, as well as semiquantitative and quantitative senile plaque and neurofibrillary tangle frequencies. Ranking of the ten cases revealed 75% inter-rater reliability among the 24 raters. Semiquantitative analyses showed reasonable inter-rater agreement, whereas quantitative measures yielded significant differences between raters for plaque and tangle counts (p < 0.0001). These differences reflected variation in stain sensitivity, staining technique (even when the same stain was used), and interpretation of the histological findings. Ratings on the cases with the highest proportions of diffuse plaques showed the greatest dependence upon stain sensitivity and variability in interpretation. This study indicates that greater attention to quality improvement is needed for the neuropathological evaluation of AD, particularly when pooling data in multicenter studies such as CERAD.

In the present study, we attempted to replicate the finding of an increased frequency of HLA-A2 in men with early-onset (less-than-or-equal-to 60 years) Alzheimer disease (AD). HLA data obtained on 167 patients (including 19 men with early-onset AD) from three geographic regions (North Carolina. Great Britain, and Finland) failed to replicate the result. A recent prospective study from Oregon, however, confirmed the association. Studies demonstrating the association suggest its presence in sporadic rather than familial AD. These results indicate a variable HLA/AD association, with some factor such as geographic region or disease familiality contributing to this variability.

The magnetic resonance scans of 22 patients with early-onset Alzheimer's disease (AD) were compared to 16 age-matched neurologically normal controls for the presence of white matter subcortical hyperintensities (SCH) and periventricular hyperintensities (PVH). Patients with AD were significantly more likely to have evidence of PVH (p < 0.01) than age-matched controls. There was no significant difference between the two groups in either the frequency of SCH or the size of the largest lesion. Within the AD group, there was no difference demonstrated in the location of the SCH, either in the anterior-posterior plane or between the two hemispheres. Patients with AD more frequently demonstrated ventriculomegaly (p < 0.001) and sulcal widening (p < 0.05) compared with controls. This study suggests that the SCH seen in early-onset AD patients on MRI are related more to the aging process than to the AD process and that the increased frequency of PVH may have a relationship to the disease process.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) was funded by the National Institute on Aging in 1986 to develop standardized, validated measures for the assessment of Alzheimer's disease (AD). The present report describes the measures that CERAD developed during its first decade and their continued use in their original and translated forms. These measures include clinical, neuropsychological, neuropathologic, and behavioral assessments of AD and also assessment of family history and parkinsonism in AD. An approach to evaluating neuroimages did not meet the standards desired. Further evaluations that could not be completed because of lack of funding (but where some materials are available) include evaluation of very severe AD and of service use and need by patient and caregiver. The information that was developed in the U.S. and abroad permits standardized assessment of AD in clinical practice, facilitates epidemiologic studies, and provides information valuable for individual and public health planning. CERAD materials and data remain available for those wishing to use them.

Although depression is known to occur in patients with Alzheimer’s disease (AD), particularly in the early stages of the dementia (Kral 1983), the frequency of this association has not been precisely determined. The role of the Dexamethasone Suppression Test (DST) in patients who have both depression and AD is likewise uncertain. Initially, patients with endogenous depression were observed to be nonsuppressors on the DST (Carroll et al. 1981), but more recent reports indicate that patients with AD but without depression may also be nonsuppressors (Spar and Gemer 1982). Some workers have suggested that this endocrine phenomenon may be related to the severity of the dementia (Jenike and Albert 1984). The patients in this study consisted of a consecutive group of 42 patients admitted to the Clinical Research Unit of Duke University Hospital for a trial of lecithii therapy for earlyonset AD (Heyman 1987). The inclusion and exclusion criteria for entry into this particular treatment study have been described (Heyman 1987). Their mean age on admission was 64.7 years, with a range of 51.5-74.7 years. The mean duration of symptoms of dementia was 3.5 years.

Objectives To evaluate the role of physical workload in low back pain (LBP) among adolescents. Methods Working history and physical workload factors at 18 years were assessed for 1984 members of the Northern Finland Birth Cohort 1986. The associations between work characteristics and LBP were analysed by multinomial logistic regression. Those with and without LBP at 18 years of age were compared in two subsamples. The incidence of LBP was studied among the 986 subjects without LBP at 16 years of age. Persistence of LBP was studied among the 728 subjects with LBP at 16 years of age. Latent class analysis (LCA) was used to form natural clusters of workload factors and their associations with LBP were investigated using log-binomial regression. Results 753 (75%) subjects without LBP at 16 years of age had been working during the 2-year follow-up period. The average duration of work was 6.2 months. In adolescent girls, working regularly or irregularly and duration of work exposure were associated with incident LBP. Of specific physical workload factors, only awkward trunk postures were associated with incident LBP in both genders (RR 1.2 in girls and 1.7 in boys). The work exposure patterns in adolescent girls and boys were different. In the LCA, subjects in a cluster with high exposure to awkward trunk postures or an overall physically demanding job had a higher likelihood of incident LBP in both genders (RR 1.3–1.9). None of the specific workload factors or clusters was associated with persistent LBP. Conclusions Physical workload factors constitute a risk for LBP even in adolescents.

We compared the clinical associations, arteriographic findings, and long-term outcome of 93 patients with amaurosis fugax and 212 patients with focal cerebral ischemia (transient ischemic attacks [TIAs]). The group of patients with cerebral TIAs included a significantly larger proportion of blacks and had a higher prevalence of hypertension than the group with amaurosis. Operable atherosclerotic lesions of the carotid arteries were more often associated with amaurosis (66%) than with cerebral TIAs (51%). The seven-year cumulative rate of cerebral infarction, however, was less in patients with amaurosis (14%) than in those with cerebral TIAs (27%; p less than 0.02). This difference in outcome persisted after adjustment for race, hypertension, and type of therapy. There were no significant differences, however, in the cumulative rates either of recurrent TIAs or of myocardial infarction or sudden death in the two groups of patients.