Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults

OBJECTIVES: To investigate the ability of cerebrospinal fluid (CSF) and plasma measures to discriminate early-stage Alzheimer disease (AD) (defined by clinical criteria and presence/absence of brain amyloid) from nondemented aging and to assess whether these biomarkers can predict future dementia in cognitively normal individuals. DESIGN: Evaluation of CSF beta-amyloid(40) (Abeta(40)), Abeta(42), tau, phosphorylated tau(181), and plasma Abeta(40) and Abeta(42) and longitudinal clinical follow-up (from 1 to 8 years). SETTING: Longitudinal studies of healthy aging and dementia through an AD research center. PARTICIPANTS: Community-dwelling volunteers (n = 139) aged 60 to 91 years and clinically judged as cognitively normal (Clinical Dementia Rating [CDR], 0) or having very mild (CDR, 0.5) or mild (CDR, 1) AD dementia. RESULTS: Individuals with very mild or mild AD have reduced mean levels of CSF Abeta(42) and increased levels of CSF tau and phosphorylated tau(181). Cerebrospinal fluid Abeta(42) level completely corresponds with the presence or absence of brain amyloid (imaged with Pittsburgh Compound B) in demented and nondemented individuals. The CSF tau/Abeta(42) ratio (adjusted hazard ratio, 5.21; 95% confidence interval, 1.58-17.22) and phosphorylated tau(181)/Abeta(42) ratio (adjusted hazard ratio, 4.39; 95% confidence interval, 1.62-11.86) predict conversion from a CDR of 0 to a CDR greater than 0. CONCLUSIONS: The very mildest symptomatic stage of AD exhibits the same CSF biomarker phenotype as more advanced AD. In addition, levels of CSF Abeta(42), when combined with amyloid imaging, augment clinical methods for identifying in individuals with brain amyloid deposits whether dementia is present or not. Importantly, CSF tau/Abeta(42) ratios show strong promise as antecedent (preclinical) biomarkers that predict future dementia in cognitively normal older adults.     

Risk of Alzheimer's disease in relatives of Parkinson's disease patients with and without dementia

OBJECTIVE: To determine whether first-degree relatives of PD patients with dementia were at increased risk for the development of AD compared with first-degree relatives of nondemented PD patients and nondemented normal subjects from the community. METHODS: A structured family history interview was administered to 146 nondemented PD patients, 120 patients with PD and dementia, and 903 normal subjects from the community to ascertain the presence of AD among parents and siblings of these subjects. Cox proportional hazards models with double censoring techniques for missing information were used to model the risk of AD among relatives. RESULTS: No increase in risk of AD was found among parents of patients with PD and dementia or parents of nondemented PD patients compared with parents of normal subjects. However, siblings of demented PD patients were three times as likely (relative risk [RR] = 3.2, 95% confidence interval [CI] = 1.1 to 9.4, p < 0.04) as siblings of normal subjects to develop AD. When only siblings >65 years of age were considered, there was a fivefold increase in risk of AD among siblings of demented PD patients compared with siblings of normal subjects (RR = 4.9, 95% CI = 1.1 to 21.4, p < 0.03). The risk of AD was also increased for female relatives, regardless of whether the woman was a relative of a demented PD patient, a nondemented PD patient, or a normal subject. Ethnicity and APOE genotype did not affect dementia status among relatives. CONCLUSIONS: The increased risk of AD in siblings of demented PD patients compared with siblings of normal subjects supports the possibility of familial aggregation of AD and PD with dementia.     

The Oregon brain aging study: neuropathology accompanying healthy aging in the oldest old

OBJECTIVE: To describe the relationship between neuropathologic aging and longitudinal measures of cognitive function in healthy oldest old individuals. METHODS: Nondemented individuals without cardiovascular or other age-associated diseases of age > or =85 years were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to clinical status, cognitive measures, and rate of cognitive change. RESULTS: Among 19 healthy individuals, 10 became demented or had incipient dementia develop. Clinical status and rate of change in cognitive scores correlated with increasing brain lesion burden, particularly in neocortical regions. Compared to demented individuals, nondemented individuals had few or no neocortical NFT (p = 0.009) or SP (p = 0.001). There was a strong correlation between rate of cognitive change on Mini-Mental State Examination (MMSE) and neocortical NFT (r = 0.859, p = 0.001). The few NFT and SP in nondemented patients had a predilection for limbic areas. CONCLUSIONS: These results support a continuum in which AD is infrequent in the healthy, cognitively stable, oldest old. The minimal abnormalities in cognitively stable individuals are consistent with the notion that preclinical pathologic AD precedes obvious cognitive impairment. Longitudinal cognitive testing shows an increased burden of neuropathologic changes in those who have cognitive decline but are not functionally impaired and do not meet criteria for the diagnosis of dementia. The strong relationship between cumulative pathologic changes and rate of cognitive decline suggests that these lesions may have clinical consequences at any age and are not likely to be benign senescent changes.     

The value of informant versus individual's complaints of memory impairment in early dementia

Self-reported versus informant-reported memory problems in nondemented elderly adults and in individuals with very mild and mild dementia of the Alzheimer type (DAT) were correlated with cognitive outcomes. No significant correlations were found between self-reported memory complaints and cognitive performance or (in controls) later development of dementia. In contrast, informant-reported memory loss distinguished nondemented from demented individuals and predicted future diagnosis of DAT.     

Clinical application of the Polish adaptation of the Montreal Cognitive Assessment (MoCA) test in screening for cognitive impairment

Background and purposeThe Montreal Cognitive Assessment (MoCA) test is a brief cognitive screening tool with high sensitivity and specificity for detecting mild cognitive impairment (MCI). The aim of this study was to evaluate the usefulness of MoCA and compare it with the Mini-Mental State Examination (MMSE) in the early detection of cognitive decline in MCI.Material and methodsA group of 115 subjects (36 meeting DSM-IV criteria for Alzheimer disease (AD) [Clinical Dementia Rating (CDR) = 1], 42 meeting Petersen's criteria for MCI [CDR = 0.5], and 37 cognitively intact controls [CDR = 0]) was recruited for the study in the university-based Alzheimer out-patient clinic. All participants underwent general medical, neurological, and psychiatric examinations. The MoCA, the MMSE, CDR and the short (15-item) version of the Geriatric Depression Scale were also applied.ResultsBoth MCI and AD groups exhibited impaired performance on MoCA compared to controls. Polish versions of the MMSE and MoCA tests were comparable in discriminating mild dementia from both MCI and control groups. The Polish version of the MoCA test performed marginally better than MMSE in discriminating MCI from controls. We propose to use the MoCA test to screen for MCI using an optimal cut-off score of 24 and to screen for dementia using a cut-off score of 19.ConclusionsThe Polish version of the MoCA seems effective in the detection of deteriorated cognitive performance and appropriate for differentiating impaired from preserved cognitive function in a Polish population.     

A brief cognitive test battery to differentiate Alzheimer's disease and frontotemporal dementia

OBJECTIVES: To validate a simple bedside test battery designed to detect mild dementia and differentiate AD from frontotemporal dementia (FTD). METHODS: Addenbrooke's Cognitive Examination (ACE) is a 100-point test battery that assesses six cognitive domains. Of 210 new patients attending a memory clinic, 139 fulfilled inclusion criteria and comprised dementia (n = 115) and nondementia (n = 24) groups. The composite and the component scores on the ACE for the two groups were compared with those of 127 age- and education-matched controls. Norms and the probability of diagnosing dementia at different prevalence rates were calculated. To evaluate the ACE's ability to differentiate early AD from FTD, scores of the cases diagnosed with dementia with a Clinical Dementia Rating < or = 1 (AD = 56, FTD = 24, others = 20) were compared. RESULTS: Two cut-off values for the ACE composite score (88 and 83) were of optimal utility depending on the target population. The ACE had high reliability, construct validity, and sensitivity (93%, using 88 as cut-off). Using the lower cut-off of 83, the ACE had a higher sensitivity (82%) and predictive value than the Mini-Mental State Examination for a wide range of dementia prevalence. The ACE differentiated AD from FTD, and the VLOM ratio (derived using component scores: [verbal fluency + language]/[orientation + memory]) of <2.2 for FTD and >3.2 for AD was highly discriminating. CONCLUSION: The ACE is a brief and reliable bedside instrument for early detection of dementia, and offers a simple objective index to differentiate AD and FTD in mildly demented patients.     

Alzheimer disease pathology in subjects without dementia in 2 studies of aging: the Nun Study and the Adult Changes in Thought Study

Individuals with antemortem preservation of cognition who show autopsy evidence of at least moderate Alzheimer disease (AD) pathology suggest the possibility of brain reserve, that is, functional resistance to structural brain damage. This reserve would, however, only be relevant if the pathologic markers correlate well with dementia. Using data from the Nun Study (n = 498) and the Adult Changes in Thought (ACT) Study (n = 323), we show that Braak staging correlates strongly with dementia status. Moreover, participants with severe(Braak stage V-VI) AD pathology who remained not demented represent only 12% (Nun Study) and 8% (ACT study) of nondemented subjects. Comparison of these subjects to those who were demented revealed that the former group was often significantly memory-impaired despite not being classified as demented. Most of these nondemented participants showed only stage V neurofibrillary pathology and frontal tangle counts that were slightly lower than a comparable (Braak stage V) dementia group. In summary, these data indicate that, in individuals with AD-type pathology who do not meet criteria for dementia, neocortical neurofibrillary tangles are somewhat reduced and incipient cognitive decline is present. Our data provide a foundation for helping to define additional factors that may impair, or be protective of, cognition in older adults.     

Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease

We compared neuropsychological findings in 28 longitudinally evaluated elderly subjects with their postmortem neuropathology, including senile plaque and neurofibrillary tangle counts from standardized sections. Nine of the subjects were not demented when evaluated just prior to their death. Numerous cortical senile plaques and other changes of Alzheimer's disease (AD) occurred in six of nine nondemented old-old subjects. Five of these six subjects had shown decline on yearly neuropsychological tests but their cognitive impairment was too mild to meet clinical criteria for dementia. Whereas cortical senile plaque count did not distinguish well between demented and nondemented subjects, every subject with numerous cortical neurofibrillary tangles was demented. The nondemented subjects with Alzheimer pathology may have had "preclinical" AD, or numerous cortical plaques may occur in some elderly subjects who would never develop clinical dementia.     

Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology

OBJECTIVE: The goal of this project was to determine whether screening different groups of elderly individuals in a general or specialty practice would be beneficial in detecting dementia. BACKGROUND: Epidemiologic studies of aging and dementia have demonstrated that the use of research criteria for the classification of dementia has yielded three groups of subjects: those who are demented, those who are not demented, and a third group of individuals who cannot be classified as normal or demented but who are cognitively (usually memory) impaired. METHODS: The authors conducted computerized literature searches and generated a set of abstracts based on text and index words selected to reflect the key issues to be addressed. Articles were abstracted to determine whether there were sufficient data to recommend the screening of asymptomatic individuals. Other research studies were evaluated to determine whether there was value in identifying individuals who were memory-impaired beyond what one would expect for age but who were not demented. Finally, screening instruments and evaluation techniques for the identification of cognitive impairment were reviewed. RESULTS: There were insufficient data to make any recommendations regarding cognitive screening of asymptomatic individuals. Persons with memory impairment who were not demented were characterized in the literature as having mild cognitive impairment. These subjects were at increased risk for developing dementia or AD when compared with similarly aged individuals in the general population. RECOMMENDATIONS: There were sufficient data to recommend the evaluation and clinical monitoring of persons with mild cognitive impairment due to their increased risk for developing dementia (Guideline). Screening instruments, e.g., Mini-Mental State Examination, were found to be useful to the clinician for assessing the degree of cognitive impairment (Guideline), as were neuropsychologic batteries (Guideline), brief focused cognitive instruments (Option), and certain structured informant interviews (Option). Increasing attention is being paid to persons with mild cognitive impairment for whom treatment options are being evaluated that may alter the rate of progression to dementia.     

CSF levels of heart fatty acid binding protein are altered during early phases of Alzheimer's disease

Heart fatty acid binding protein (HFABP) has been proposed as a putative marker for dementia disorders. To evaluate the value of this protein as an early marker of Alzheimer's disease (AD), we analyzed HFABP level and the classical biomarkers amyloid-β (Aβ)1-42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) followed up for four years (n=41), AD (n=32), and subjects with other neurological diseases without dementia (OND, n=25). HFABP levels were higher in AD patients and in MCI converting to AD (MCI-AD) with respect to OND and to cognitively stable MCI patients (MCI-MCI). The receiver operator characteristics analysis for HFABP alone showed a sensitivity of 87% and a specificity of 81% for AD versus OND (area under the curve, AUC=0.83); sensitivity and specificity were 46% and 94%, respectively, when comparing MCI-MCI versus MCI-AD. CSF HFABP levels showed a strong positive correlation with both t-tau and p-tau. Interestingly, the ratio between HFABP and Aβ1-42 improved the performance in distinguishing AD from OND (sensitivity: 90%; specificity 82%, AUC=0.89), and gave the best accuracy in discriminating MCI-AD from MCI-MCI (sensitivity: 80%; specificity 100%, AUC=0.90). Survival analysis by means of Kaplan-Meier curve showed a significantly higher proportion of MCI patients converting to AD in the group with higher values of HFABP/Aβ1-42 ratio (cut-off=0.7). A significant correlation between HFABP/Aβ1-42 ratio and MMSE annual decrease rate was also documented (p<0.0001). HFABP /Aβ1-42 ratio might be a useful predictor of conversion in MCI patients.     

Absence of cognitive impairment or decline in preclinical Alzheimer's disease

OBJECTIVE: To determine whether clinically nondemented elderly individuals with pathologically confirmed preclinical AD are characterized by cognitive decline as measured by psychometric tests before death. METHODS: Psychometric performance was examined retrospectively in 14 individuals who were nondemented at time of death and grouped in accordance with their neuropathologic findings: 1) Healthy brain (n = 9) was characterized by the absence of senile plaques or by only patchy neocortical deposits of plaques; 2) preclinical AD (n = 5) was characterized by neuritic and diffuse plaques distributed throughout the neocortex. All individuals showed neurofibrillary pathologic change in medial temporal lobe structures. For comparison, we also evaluated 10 individuals who died in the earliest symptomatic stage of dementia of the Alzheimer type (DAT). All individuals had been assessed by clinical and psychometric measures during life. The psychometric measures yielded a standardized factor score that represented global cognitive performance. RESULTS: At the last assessment before death, individuals with very mild DAT were impaired on the factor score and on individual psychometric measures with respect to the nondemented individuals. Those nondemented individuals with preclinical AD did not differ in performance from those with healthy brains. For individuals with at least three psychometric assessments during life, there was no decline in performance for either those with healthy brains (n = 5) or preclinical AD (n = 3), although decline was evident for very mild DAT individuals (n = 5). CONCLUSIONS: Pathologically confirmed preclinical AD is not associated with cognitive impairment or decline, even on measures shown to be sensitive to very mild DAT.     

Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun Study

OBJECTIVE: To determine whether hippocampal volume is a sensitive and specific indicator of Alzheimer neuropathology, regardless of the presence or absence of cognitive and memory impairment. METHODS: Postmortem MRI scans were obtained for the first 56 participants of the Nun Study who were scanned. The area under receiver operating characteristic curves, sensitivity, specificity, and positive and negative predictive values were used to assess the diagnostic accuracy of hippocampal volume in predicting fulfillment of Alzheimer neuropathologic criteria and differences in Braak staging. RESULTS: Hippocampal volume predicted fulfillment of neuropathologic criteria for AD for all 56 participants (p < 0.001): 24 sisters who were demented (p = 0.036); 32 sisters who remained nondemented (p < 0.001), 8 sisters who remained nondemented but had memory impairment (p < 0.001), and 24 sisters who were intact with regard to memory and cognition at the final examination prior to death (p = 0.003). In individuals who remained nondemented, hippocampal volume was a better indicator of AD neuropathology than a delayed memory measure. Among nondemented sisters, Braak stages III and VI were distinguishable from Braak stages II or lower (p = 0.001). Among cognitively intact individuals, those in Braak stage II could be distinguished from those in stage I or less (p = 0.025). CONCLUSION: Volumetric measures of the hippocampus may be useful in identifying nondemented individuals who satisfy neuropathologic criteria for AD as well as pathologic stages of AD that may be present decades before initial clinical expression.     

Utility of a modified Mini-Mental State Examination with extended delayed recall in screening for mild cognitive impairment and dementia among community dwelling elders

The objective of this study was to test the utility of additional delayed recall of the three recall items of the Folstein Mini Mental State Evaluation (MMSE) as a screening measure for mild cognitive impairment and dementia in the elderly. It used a cross-sectional study of subjects, who were administered a brief memory screening battery which included the MMSE and extended delayed recall of the three MMSE recall items at 5 minute intervals. The criteria for cognitive status was determined on the basis of the neurological and neuropsychological evaluation. One hundred and two elderly persons who were recruited through a memory screening program were diagnosed as cognitively normal (N=52), mild cognitively impaired (N=24), or demented (N=26). The observed sensitivity of 83.3% and specificity of 90.4% was achieved across three delayed recall trials in differentiating cases with mild cognitive impairment (without dementia) from individuals with normal cognition and was superior to the total MMSE score alone (sensitivity/specificity: 70.8%/84.6%). Cumulative recall for the three MMSE items across only two delayed recall trials demonstrated a sensitivity of 96.2% and specificity of 90.4% in differentiating between cases of dementia versus cases diagnosed with no cognitive impairment. The three trial delayed recall score enhanced prediction of mild cognitive impairment in at-risk elderly living with the community and may have promise in the development of future screening batteries.     

Predicting development of dementia in the elderly with the Selective Reminding Test

The ability to predict the development of dementia through the detection of memory impairment in nondemented individuals was assessed with the Selective Reminding Test (SR), a popular test of verbal memory functioning in the elderly. The SR was administered to 385 nondemented volunteer subjects (mean age = 80.4 years) enrolled in a longitudinal study of risk factors in the development of dementia. Of these, 36 subjects ultimately became demented. SR scores obtained from 1 to 2 years prior to the diagnosis of dementia were compared with a set of previously established cutoff scores derived from a cognitively normal elderly sample. The results demonstrated that sum of recall and delayed recall were the SR measures best able to predict dementia with sensitivities of 47% and 44%, respectively. The predictive values were 37% and 40%, respectively, or better than two-and-one-half times the base rate. The contributions of both the SR Test and the Fuld Object-Memory Test (OM) were discussed in terms of the further understanding of the characteristics of the preclinical phase of dementia.     

Rates of progression in mild cognitive impairment and early Alzheimer's disease

OBJECTIVE: To compare rates of progression in the very mildest stages of AD, including the stage currently identified as mild cognitive impairment (MCI), and to identify predictors of those rates. METHODS: Demented (n = 289) and nondemented (n = 230) individuals enrolled in longitudinal studies at an Alzheimer Disease Research Center received annual clinical and psychometric examinations for up to 20 years. In order of increasing dementia severity, demented individuals were diagnosed with incipient, very mild, or mild dementia; the incipient stage is equivalent to MCI. Outcome measures included death, nursing home placement, and psychometric scores. RESULTS: Rate of progression increased with dementia severity as staged by the Clinical Dementia Rating at entry into the study. With respect to the dichotomous outcomes, the increase with dementia severity was more dramatic for the endpoint of nursing home entry than it was for the endpoint of death. Increased rates of cognitive decline with increased dementia severity were also obtained for psychometric scores. There was limited evidence of other predictors of progression. CONCLUSIONS: The lack of effective predictors of the rate of dementia progression extends to the very earliest stages of the disease, including what is often called MCI. A new approach to the identification of correlates of rates of progression is needed.     

Excess functional disability among demented subjects? Findings from the Canadian Study of Health and Aging

Dementia has been recognized as the strongest determinant for developing functional disability. However, dementia patients typically present with concomitant illness, thereby making difficult a determination of the fraction of disability due to dementia. The objective of this study was to estimate the prevalence of functional disability among demented and nondemented people and to estimate the excess disability in demented subjects net of conditions independently associated with disability in older people, using data on nearly 2,900 subjects from the clinical examination of the 1991 Canadian Study of Health and Aging. Unadjusted specific disability prevalence (in bathing, dressing, grooming, toileting and stool and urinary incontinence) is considerably greater among demented subjects than among cognitively normal or cognitively impaired but not demented subjects. After adjustments, specific disability in demented subjects is somewhat reduced in comparison to nondemented and cognitively impaired but not demented subjects. Thus, even when one considers the influence of a history of physical illnesses that typically result in disability, the link between disability and dementia is only marginally attenuated.     

Coexisting depression and dementia in a community survey of the elderly

We report here on the coexistence of dementia and depression in a community population aged 75 years and older. Complete information about mood and cognition was available for 286 cognitively intact subjects selected for assessment because of their low scores on the Mini-Mental State, and for 158 mildly and moderately demented subjects. Severely demented subjects, who were incapable of providing information, were excluded. Five percent (8/158) of demented subjects also fulfilled criteria for major depressive disorder Diagnostic and Statistical Manual of Mental Disorders, third edition (DSM-III) compared with 9% (27/286) of cognitively intact subjects. No substantial differences existed in the symptoms reported by demented depressives and nondemented depressives, but subjects who suffered from both disorders were so markedly apathetic that their depression might easily have been overlooked had specific enquiries not been made. Depression was particularly associated with dementia secondary to multi-infarct and Parkinson's disease. When reviewed one year later, 2 of the 18 surviving depressed, nondemented subjects showed evidence of dementia. Both presented unusual diagnostic difficulties, however, and no evidence emerged that large numbers of elderly people will be misclassified in community surveys that include a mental state examination, cognitive testing, and an informant interview.     

Category fluency as a screening test for Alzheimer disease in illiterate and literate patients

Brief cognitive tests are widely used for dementia screening, but are usually influenced by education. The present work aimed to determine education-adjusted cut-off scores and correspondent sensitivity (S) and specificity (Sp) values of the category fluency (CF) test (animals/min) as a screening tool for Alzheimer disease (AD). Eighty-eight patients with mild AD and 117 normal matched controls were evaluated. Patients and controls were divided into 4 groups according to educational level (illiterates, 1 to 3, 4 to 7, and > or =8 y) and were administered the CF test. In each group, cut-off values were determined using Receiver Operator Characteristic analysis. The areas under Receiver Operator Characteristic curves were 0.922/0.914/0.963/0.954, for the identification of AD among the groups of illiterates, 1 to 3, 4 to 7, and > or =8 years of education, respectively. The cut-off points for each group were 9 (S=90.5% and Sp=80.6%) for illiterates; 12 (S=95.2%% and Sp=80.0%) for 1 to 3 years; 12 (S=91.3% and Sp=91.9%) for 4 to 7 years, and 13 for those with > or =8 years (S=82.6% and Sp=100.0%). These results suggest that the CF may be a useful screening test for mild AD in different educational levels, with the need of using specific cut-off scores adjusted for each range of schooling.     

Patient's rating of cognitive ability: using the AD8, a brief informant interview, as a self-rating tool to detect dementia

OBJECTIVE: To test the ability of patients to rate their own cognitive ability using the AD8 compared with informant and clinician ratings of cognitive status. DESIGN, SETTING, AND PATIENTS: The AD8 was administered to 325 consecutive participant-informant dyads enrolled in a longitudinal study at Washington University School of Medicine between April 4, 2005, and December 15, 2005. The number of AD8 items endorsed by the participant was compared with informant answers and an independently derived Clinical Dementia Rating. MAIN OUTCOME MEASURE: Strength of association was measured with Spearman (rho) and intraclass correlation coefficients. Receiver operator characteristic curves assessed the discriminative properties of the AD8. RESULTS: The mean age of participants and informants was 72.8 years (range, 43-104 years) and 66.4 years (range, 24-101 years), respectively. The Clinical Dementia Rating was correlated with both informant (rho = 0.75, P<.001) and participant (rho = 0.34, P<.001) AD8 scores. Participants' AD8 scores had adequate agreement with informants' AD8 scores (intraclass correlation coefficient, 0.53; 95% confidence interval, 0.41-0.62) and correlated with subjective complaints of memory problems (rho = 0.47, P<.001) but not with estimates of symptom duration. The area under the receiver operator characteristic curve for the informant AD8 was 0.89 (95% confidence interval, 0.86-0.93); for the participant AD8, it was 0.78 (95% confidence interval, 0.68-0.78). CONCLUSIONS: The AD8 is a brief measure that, when completed by an informant, differentiates nondemented from demented individuals. We now demonstrate that a self-completed AD8 also differentiates nondemented from demented individuals, although the utility was better in mildly impaired individuals compared with more demented individuals. In the absence of a reliable informant, the AD8 may be asked of the participant to gain an understanding of their perception of cognitive status.     

The relative frequency of "dementia of unknown etiology" increases with age and is nearly 50% in nonagenarians

CONTEXT: With the recent change in pathological criteria for Alzheimer disease (AD), a group of patients has emerged who do not meet pathological criteria for any well-characterized degenerative dementias. Whether these unclassified patients have vascular dementia or some other form of dementia is not known. OBJECTIVE: To determine the clinical characteristics, pathological substrate, and relative frequency of dementia not caused by well-characterized degenerative dementias. DESIGN/SETTING: Clinicopathological study of a prospectively observed sample of elderly nondemented and demented subjects recruited from our urban community. METHODS: In our series of 128 subjects with prospective neuropsychological evaluations as well as neuropathology, we identified 35 clinically nondemented subjects and 20 demented patients who did not meet pathological criteria for well-characterized degenerative dementias such as AD or dementia with Lewy bodies. The 20 demented patients were grouped together under the term dementia of unknown etiology (DUE). We compared clinical, genetic, neuropsychological, pathological, and neurochemical characteristics of the nondemented group, patients with DUE, and 28 patients with AD and no other pathological abnormality. RESULTS: Mean age at death for patients with DUE was 89.1 +/- 5.8 years compared with 79.9 +/- 11.4 years for AD (P<.001). Patients with AD and DUE did not differ in sex, risk factors, apolipoprotein E genotype, neuropsychological features, or neurological features. Hippocampal sclerosis (in 11 patients with dementia and no controls) and leukoencephalopathy (in 7 patients with dementia and 1 control) were associated with cognitive impairment; other vascular markers were not. Dementia of unknown etiology accounted for 5% of all cases of dementia among patients dying in their 70s, 21% for patients dying in their 80s, and 48% for patients dying in their 90s. CONCLUSIONS: A significant percentage of demented patients older than 80 years do not meet pathological criteria for AD or dementia with Lewy bodies. Hippocampal sclerosis and leukoencephalopathy are common in these patients but rare in clinically nondemented subjects.