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Brain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear. Cross-sectional and longitudinal resting-state functional magnetic resonance imaging data from both Chinese and Western populations were analyzed. We proposed a framework of dynamic proportional loss of functional connectivity (DPLFC). After its stability was validated, the optimal parameters were applied for the clinical diagnosis of SCD. DPLFC yielded a relatively high intraclass correlation coefficient. In particular, the DPLFC of the left superior frontal gyrus (SFG) progressively decreased along the Alzheimer's disease (AD) continuum. Compared with the traditional index, the DPLFC had better classification performance between cognitively normal controls and patients with SCD. Furthermore, DPLFC was related to Aβ deposition and scale scores. Patients with lower DPLFC values had a greater risk of cognitive decline. Decreased DPLFC in the left SFG may be a potential AD-related neuroimaging biomarker at an early stage., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to American Aging Association.)

Objectives: Identify which NIH Toolbox Cognition Battery (NIHTB-CB) subtest(s) best differentiate healthy controls (HC) from those with amnestic mild cognitive impairment (aMCI) and compare the discriminant accuracy between a model using a priori "Norm Adjusted" scores versus "Unadjusted" standard scores with age, sex, race/ethnicity, and education controlled for within the model. Racial differences were also examined., Methods: Participants were Black/African American (B/AA) and White consensus-confirmed (HC = 96; aMCI = 62) adults 60-85 years old that completed the NIHTB-CB for tablet. Discriminant function analysis (DFA) was used in the Total Sample and separately for B/AA ( n = 80) and White participants ( n = 78)., Results: Picture Sequence Memory (an episodic memory task) was the highest loading coefficient across all DFA models. When stratified by race, differences were noted in the pattern of the highest loading coefficients within the DFAs. However, the overall discriminant accuracy of the DFA models in identifying HCs and those with aMCI did not differ significantly by race (B/AA, White) or model/score type (Norm Adjusted versus Unadjusted)., Conclusions: Racial differences were noted despite the use of normalized scores or demographic covariates-highlighting the importance of including underrepresented groups in research. While the models were fairly accurate at identifying consensus-confirmed HCs, the models proved less accurate at identifying White participants with an aMCI diagnosis. In clinical settings, further work is needed to optimize computerized batteries and the use of NIHTB-CB norm adjusted scores is recommended. In research settings, demographically corrected scores or within model correction is suggested.

We sought to determine whether the biomarkers of chronic inflammation predict cognitive decline in a prospective observational study. We measured baseline serum soluble urokinase plasminogen activator receptor (suPAR) and high sensitivity C-reactive protein (hs-CRP) levels in 282 participants of the University of Michigan Memory and Aging Project. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Clinical Dementia Rating (CDR) scale for up to five time points. SuPAR and hs-CRP levels were not significantly higher in participants with mild cognitive impairment ( n  = 97) or dementia ( n  = 59), compared to those with normal cognitive function ( n  = 126). Overall, 14% of participants experienced significant cognitive decline over the study period. The change in MoCA or CDR scores over time did not differ significantly according to baseline suPAR or hs-CRP levels. Chronic systemic inflammation, as measured by serum suPAR or hs-CRP levels, is unlikely to contribute significantly to cognitive decline., Competing Interests: SSH is a member of the scientific advisory board of Walden Biosciences. Other authors do not have a conflict of interest. Author disclosures are available in the supporting information., (© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

When the US Food and Drug Administration used the accelerated approval process to authorize the use of the antiamyloid drug aducanumab to treat Alzheimer's disease (AD), many people hoped this signaled a new era of disease-modifying treatment. But 2 years later, aducanumab's failure to launch provides a cautionary tale about the complexities of dementia and the need for a thorough and transparent review of the role that regulatory agencies and various stakeholders play in approving AD drugs. We highlight the events leading to aducanumab's controversial approval and discuss some of the key lessons learned from the drug's failure to deliver the hoped-for benefits. These lessons include the inherent limitations of antiamyloid strategies for a complex disease in which amyloid is only one of several pathological processes, the need for clinical trials that better reflect the diversity of communities affected by AD, the potential pitfalls of futility analyses in clinical trials, the need for greater transparency and other modifications to the approval process, and the dementia field's unreadiness to move from the highly controlled environment of clinical trials to the widespread and chronic use of resource-intensive, disease-modifying drugs in real-world treatment scenarios. People with dementia desperately need effective therapies. We hope that the aducanumab story will inspire changes to the approval process-changes that restore public trust and improve future efforts to deliver disease-modifying therapies to the clinic.

Background: Converging evidence suggests that markers of Alzheimer's disease (AD) pathology in cognitively unimpaired older individuals are associated with high risk of cognitive decline and progression to functional impairment. The Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) and Longitudinal Evaluation of Amyloid and Neurodegeneration Risk (LEARN) Studies enrolled a large cohort of cognitively normal older individuals across a range of baseline amyloid PET levels. Recent advances in AD blood-based biomarkers further enable the comparison of baseline markers in the prediction of longitudinal clinical outcomes., Objectives: We sought to evaluate whether biomarker indicators of higher levels of AD pathology at baseline predicted greater cognitive and functional decline, and to compare the relative predictive power of amyloid PET imaging, tau PET imaging, and a plasma P-tau217 assay., Design: All participants underwent baseline amyloid PET scan, plasma P-tau217; longitudinal cognitive testing with the Primary Alzheimer Cognitive Composite (PACC) every 6 months; and annual functional assessments with the clinical dementia rating (CDR), cognitive functional index (CFI), and activities of daily living (ADL) scales. Baseline tau PET scans were obtained in a subset of participants. Participants with elevated amyloid (Aβ+) on screening PET who met inclusion/exclusion criteria were randomized to receive placebo or solanezumab in a double-blind phase of the A4 Study over 240+ weeks. Participants who did not have elevated amyloid (Aβ-) but were otherwise eligible for the A4 Study were referred to the companion observational LEARN Study with the same outcome assessments over 240+ weeks., Setting: The A4 and LEARN Studies were conducted at 67 clinical trial sites in the United States, Canada, Japan and Australia., Participants: Older participants (ages 65-85) who were cognitively unimpaired at baseline (CDR-GS=0, MMSE 25-30 with educational adjustment, and Logical Memory scores within the normal range LMIIa 6-18) were eligible to continue in screening. Aβ+ participants were randomized to either placebo (n=583) or solanezumab (n=564) in the A4 Study. A subset of Aβ+ underwent tau PET imaging in A4 (n=350). Aβ- were enrolled into the LEARN Study (n=553)., Measurements: Baseline 18-F Florbetapir amyloid PET, 18-F Flortaucipir tau PET in a subset and plasma P-tau217 with an electrochemiluminescence (ECL) immunoassay were evaluated as predictors of cognitive (PACC), and functional (CDR, CFI and ADL) change. Models were evaluated to explore the impact of baseline tertiles of amyloid PET and tertiles of plasma P-tau217 on cognitive and functional outcomes in the A4 Study compared to LEARN. Multivariable models were used to evaluate the unique and common variance explained in longitudinal outcomes based on baseline predictors, including effects for age, gender, education, race/ethnic group, APOEε4 carrier status, baseline PACC performance and treatment assignment in A4 participants (solanezumab vs placebo)., Results: Higher baseline amyloid PET CL and P-tau217 levels were associated with faster rates of PACC decline, and increased likelihood of progression to functional impairment (CDR 0.5 or higher on two consecutive measurements), both across LEARN Aβ- and A4 Aβ+ (solanezumab and placebo arms). In analyses considering all baseline predictor variables, P-tau217 was the strongest predictor of PACC decline. Among participants in the highest tertiles of amyloid PET or P-tau217, >50% progressed to CDR 0.5 or greater. In the tau PET substudy, neocortical tau was the strongest predictor of PACC decline, but plasma P-tau217 contributed additional independent predictive variance in commonality variance models., Conclusions: In a large cohort of cognitively unimpaired individuals enrolled in a Phase 3 clinical trial and companion observational study, these findings confirm that higher baseline levels of amyloid and tau markers are associated with increased rates of cognitive decline and progression to functional impairment. Interestingly, plasma P-tau217 was the best predictor of decline in the overall sample, superior to baseline amyloid PET. Neocortical tau was the strongest predictor of cognitive decline in the subgroup with tau PET, suggesting that tau deposition is most closely linked to clinical decline. These findings indicate that biomarkers of AD pathology are useful to predict decline in an older asymptomatic population and may prove valuable in the selection of individuals for disease-modifying treatments., Competing Interests: RAS reports grant support from the National Institutes on Aging, National Institutes of Health, Alzheimer’s Association, GHR Foundation, and Gates Ventures. She has received trial research funding from Eisai and Eli Lilly for public-private partnership trials. She reported serving as a consultant for AbbVie, AC Immune, Alector, Biohaven, Bristol-Myers-Squibb, Ionis, Janssen, Genentech, Merck, Prothena, Roche, and Vaxxinity. MCD has received research funding from the National Institutes of Health, Janssen, Eli Lilly, and Eisai, reports consulting fees from Roche and his spouse is a full-time employee of Janssen. KAJ has received research funding from National Institutes on Aging, National Institutes of Health, Alzheimer’s Association, and the GHR Foundation. He has served as a consultant for Merck, Novartis, Janssen, and Prothena. RAR has research support from the National Institute on Aging, the Alzheimer’s Association and is a consultant for Amydis Inc, Bioivt, Lexeo, Keystone Bio, Allyx, DiamiR, Ionis and PrecisionMed. CJ has received research support from the National Institutes of Health (NIH), the Alzheimer’s Association, American Heart Association, Eli Lilly and Eisai. DMR received salary and research support from the National Institutes of Health and has received payment or honoraria from USC Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT AD) course and External Advisory Boards from the University of California-Davis, Washington University, Boston University and Northwestern. She has also received travel support to ACTC meetings, to the University of California Advisory Board Meeting and the Washington University Advisory Board Meeting. JG has received research support from the National Institutes of Health (NIH), the Alzheimer’s Association, BrightFocus Foundation, Eli Lilly, Biogen, Genentech, and Eisai. He has received personal fees for providing consulting to SiteRx and editorial service to Alzheimer’s and Dementia. JLH has received research support from the National Institutes of Health, the Alzheimer’s Association, Eli Lilly, and Eisai and has received honoraria from USC Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT AD) RR has received research support from the National Institutes of Health (NIH), the Alzheimer’s Association, American Heart Association, Eli Lilly and Eisai. AL has received research support from the National Institutes of Health (NIH), the Alzheimer’s Association, American Heart Association, Eli Lilly and Eisai. OL has received research support from the National Institutes of Health (NIH), the Alzheimer’s Association, American Heart Association, Eli Lilly and Eisai. GJM has received research support from the National Institutes of Health (NIH), the Alzheimer’s Association, American Heart Association, Gates Ventures, Eli Lilly, and Eisai. RY is an employee and minor shareholder of Eli Lilly and Company. KCH is an employee and minor shareholder of Eli Lilly and Company. JS is an employee and minor shareholder of Eli Lilly and Company. PSA has received grants or contracts from the National Institutes of Health (NIH), Alzheimer’s Association, Foundation for NIH (FNIH), Lilly, Janssen and Eisai and consulting fees from Merck, Biogen, AbbVie, Roche, and Immunobrain Checkpoint.

Background: Early detection is necessary for the treatment of dementia. Computerized testing has become more widely used in clinical trials; however, it is unclear how sensitive these measures are to early signs of neurodegeneration. We investigated the use of the NIH Toolbox-Cognition (NIHTB-CB) and Cogstate-Brief computerized neuropsychological batteries in the identification of mild cognitive impairment (MCI) versus healthy older adults [healthy control (HC)] and amnestic (aMCI) versus nonamnestic MCI (naMCI). Exploratory analyses include investigating potential racial differences., Methods: Two hundred six older adults were diagnosed as aMCI (n = 58), naMCI (n = 15), or cognitively healthy (HC; n = 133)., Results: The NIH Toolbox-CB subtests of Flanker, Picture Sequence Memory, and Picture Vocabulary significantly differentiated MCI from HC. Further, subtests from both computerized batteries differentiated patients with aMCI from those with naMCI. Although the main effect of race differences was noted on tests and in diagnostic groups was significant, there were no significant race-by-test interactions., Conclusions: Computer-based subtests vary in their ability to help distinguish MCI subtypes, though these tests provide less expensive and easier-to-administer clinical screeners to help identify patients early who may qualify for more comprehensive evaluations. Further work is needed, however, to refine computerized tests to achieve better precision in distinguishing impairment subtypes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A blood test for Alzheimer's disease is now available for clinical use in persons with cognitive impairment. This is an extraordinary milestone, though the amyloid-based PrecivityAD™ test is not without limitations. Pre and post-test counseling are essential. Phosphorylated tau blood tests are likely to follow soon. When used in conjunction with an appropriate clinical evaluation, blood tests provide the opportunity for an early, accurate, and accessible diagnosis of Alzheimer's disease. Standalone use, however, carries a significant risk of misinterpretation and is strongly discouraged. Now is the time to develop appropriate use criteria to guide the use of these promising assays.

Background: Frontotemporal dementia (FTD) is the second most common cause of early-onset neurodegenerative dementia. Several studies have focused on early imaging changes in FTD patients, but once subjects meet full criteria for FTD diagnosis, structural changes are generally widespread., Objective: This study aims to determine the earliest structural brain changes in asymptomatic MAPT MUTATION carriers., Methods: This is a cross-sectional multicenter study comparing global and regional brain volume and white matter integrity in a group of MAPT mutation preclinical carriers and controls. Participants belong to multiple generations of six families with five MAPT mutations. All participants underwent a medical examination, neuropsychological tests, genetic analysis, and a magnetic resonance scan (3T, scout, T1-weighted image followed by EPI (BOLD), MPRAGE, DTI, FLAIR, and ASL sequences)., Results: Volumes of five cortical and subcortical areas were strongly correlated with mutation status: temporal lobe (left amygdala, left temporal pole), cingulate cortex (left rostral anterior cingulate gyrus, right posterior cingulate), and the lingual gyrus in the occipital lobe. We did not find significant differences in whole brain volume, white matter hyperintensities volume, and white matter integrity using DTI analysis., Conclusion: Temporal lobe, cingulate cortex and the lingual gyrus seem to be early targets of the disease and may serve as biomarkers for FTD prior to overt symptom onset.

Background: Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD., Methods: The Veterans Affairs Cooperative Studies Program initiated a multicenter, randomized, double-blind, placebo-controlled trial in August 2007, with enrollment through March 2012 and follow-up continuing through September 2012. Participants with mild-to-moderate AD who were taking an acetylcholinesterase inhibitor were assigned randomly to 2000 IU/day of alpha-tocopherol, 20 mg/day memantine, 2000 IU/day alpha-tocopherol plus 20 mg/day memantine, or placebo. The primary outcome for the study is the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory. Secondary outcome measures include the Mini-Mental State Examination; the Alzheimer's Disease Assessment Scale, cognitive portion; the Dependence Scale; the Neuropsychiatric Inventory; and the Caregiver Activity Survey. Patient follow-up ranged from 6 months to 4 years., Results: A total of 613 participants were randomized. The majority of the patients were male (97%) and white (86%), with a mean age of 79 years. The mean Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory score at entry was 57 and the mean Mini-Mental State Examination score at entry was 21., Conclusion: This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013., (Published by Elsevier Inc.)

Importance: Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD., Objective: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor., Design, Setting, and Participants: Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers., Interventions: Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152)., Main Outcomes and Measures: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures., Results: Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants)., Conclusions and Relevance: Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden., Trial Registration: clinicaltrials.gov Identifier: NCT00235716.

Background: Caregivers of patients with mild cognitive impairment (MCI) need similar levels of support services as Alzheimer's disease (AD) caregivers, but it is unclear if this translates to increased caregiver burden., Methods: 135 participants and their caregivers (40 MCI, 55 AD and 40 normal controls, NC) completed questionnaires, and the patients were administered neuropsychological tests., Results: The MCI caregivers reported significantly more overall caregiving burden than the NC, but less than the AD. They showed similar levels of emotional, physical and social burden as the AD caregivers. Among the MCI caregivers, the neuropsychiatric symptoms and executive functioning of the patients were related to a greater burden, and the caregivers with a greater burden reported lower life satisfaction and social support, and a greater need for support services., Conclusion: These results indicate that MCI caregivers are at increased risk for caregiver stress, and they require enhanced assistance and/or education in caring for their loved ones., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To evaluate the cause of diagnostic errors in the visual interpretation of positron emission tomographic scans with fludeoxyglucose F 18 (FDG-PET) in patients with frontotemporal lobar degeneration (FTLD) and patients with Alzheimer disease (AD)., Design: Twelve trained raters unaware of clinical and autopsy information independently reviewed FDG-PET scans and provided their diagnostic impression and confidence of either FTLD or AD. Six of these raters also recorded whether metabolism appeared normal or abnormal in 5 predefined brain regions in each hemisphere-frontal cortex, anterior cingulate cortex, anterior temporal cortex, temporoparietal cortex, and posterior cingulate cortex. Results were compared with neuropathological diagnoses., Setting: Academic medical centers., Patients: Forty-five patients with pathologically confirmed FTLD (n=14) or AD (n=31)., Results: Raters had a high degree of diagnostic accuracy in the interpretation of FDG-PET scans; however, raters consistently found some scans more difficult to interpret than others. Unanimity of diagnosis among the raters was more frequent in patients with AD (27 of 31 patients [87%]) than in patients with FTLD (7 of 14 patients [50%]) (P=.02). Disagreements in interpretation of scans in patients with FTLD largely occurred when there was temporoparietal hypometabolism, which was present in 7 of the 14 FTLD scans and 6 of the 7 scans lacking unanimity. Hypometabolism of anterior cingulate and anterior temporal regions had higher specificities and positive likelihood ratios for FTLD than temporoparietal hypometabolism had for AD., Conclusions: Temporoparietal hypometabolism in FTLD is common and may cause inaccurate interpretation of FDG-PET scans. An interpretation paradigm that focuses on the absence of hypometabolism in regions typically affected in AD before considering FTLD is likely to misclassify a significant portion of FTLD scans. Anterior cingulate and/or anterior temporal hypometabolism indicates a high likelihood of FTLD, even when temporoparietal hypometabolism is present. Ultimately, the accurate interpretation of FDG-PET scans in patients with dementia cannot rest on the presence or absence of a single region of hypometabolism but rather must take into account the relative hypometabolism of all brain regions.

Background: The clinical diagnosis of dementing diseases largely depends on the subjective interpretation of patient symptoms. Consensus panels are frequently used in research to determine diagnoses when definitive pathologic findings are unavailable. Nevertheless, research on group decision making indicates that many factors can adversely affect panel performance., Objective: To determine conditions that improve consensus panel diagnosis., Design: Comparison of neuropathologic diagnoses with individual and consensus panel diagnoses based on clinical scenarios only, fludeoxyglucose F 18 positron emission tomography images only, and scenarios plus images., Setting: Expert and trainee individual and consensus panel deliberations using a modified Delphi method in a pilot research study of the diagnostic utility of fludeoxyglucose F 18 positron emission tomography., Patients: Forty-five patients with pathologically confirmed Alzheimer disease or frontotemporal dementia., Main Outcome Measures: Statistical measures of diagnostic accuracy, agreement, and confidence for individual raters and panelists before and after consensus deliberations., Results: The consensus protocol using trainees and experts surpassed the accuracy of individual expert diagnoses when clinical information elicited diverse judgments. In these situations, consensus was 3.5 times more likely to produce positive rather than negative changes in the accuracy and diagnostic certainty of individual panelists. A rule that forced group consensus was at least as accurate as majority and unanimity rules., Conclusions: Using a modified Delphi protocol to arrive at a consensus diagnosis is a reasonable substitute for pathologic information. This protocol improves diagnostic accuracy and certainty when panelist judgments differ and is easily adapted to other research and clinical settings while avoiding the potential pitfalls of group decision making.

Little is known about the service needs for persons caring for individuals with mild cognitive impairment (MCI). In this study, the level of support service need for caregivers of individuals diagnosed with Alzheimer disease (AD; N=55) and MCI (N=25) was compared with normal controls (N=44). Study partners (ie, caregivers) completed questionnaires about their service needs and participants' neurobehavioral symptoms, functional abilities, and frailty. Total, social, and mental health service needs were significantly different among the 3 groups (P<0.0001), with MCI and AD caregivers reporting more need for services as compared with the normal control group. There was no significant difference between MCI and AD groups for total and social service need. In the MCI group, caregiver's service need was related to neurobehavioral symptoms and frailty, whereas service need among the AD caregivers was related to functional disability and frailty. Caregivers of individuals with MCI are already experiencing a need for increased services comparable to that of individuals caring for AD patients, though the pattern of patient-related factors is different between the 2 patient groups. These findings suggest possible areas of intervention that could be considered at the earliest stages of memory loss.

Distinguishing Alzheimer's disease (AD) and frontotemporal dementia (FTD) currently relies on a clinical history and examination, but positron emission tomography with [(18)F] fluorodeoxyglucose (FDG-PET) shows different patterns of hypometabolism in these disorders that might aid differential diagnosis. Six dementia experts with variable FDG-PET experience made independent, forced choice, diagnostic decisions in 45 patients with pathologically confirmed AD (n = 31) or FTD (n = 14) using five separate methods: (1) review of clinical summaries, (2) a diagnostic checklist alone, (3) summary and checklist, (4) transaxial FDG-PET scans and (5) FDG-PET stereotactic surface projection (SSP) metabolic and statistical maps. In addition, we evaluated the effect of the sequential review of a clinical summary followed by SSP. Visual interpretation of SSP images was superior to clinical assessment and had the best inter-rater reliability (mean kappa = 0.78) and diagnostic accuracy (89.6%). It also had the highest specificity (97.6%) and sensitivity (86%), and positive likelihood ratio for FTD (36.5). The addition of FDG-PET to clinical summaries increased diagnostic accuracy and confidence for both AD and FTD. It was particularly helpful when raters were uncertain in their clinical diagnosis. Visual interpretation of FDG-PET after brief training is more reliable and accurate in distinguishing FTD from AD than clinical methods alone. FDG-PET adds important information that appropriately increases diagnostic confidence, even among experienced dementia specialists.

Flurodeoxyglucose positron emission tomography (FDG-PET) is being explored to determine its ability to differentiate between a diagnosis of Alzheimer's disease (AD) and fronto-temporal dementia (FTD). We have examined statistical discrimination procedures to help achieve this purpose and compared the results to visual ratings of FDG-PET images. The methods are applied to a data set of 48 subjects with autopsy confirmed diagnoses of AD or FTD (these subjects come from a multi-centre collaborative study funded by the National Alzheimer's Coordinating Center). FDG-PET images are composed of thousands of voxels (volume elements) so one is left with a situation where there are vastly more variables than subjects. Therefore, it is necessary to perform a data reduction before a statistical procedure can be applied. Approaches using both the entire image and summary statistics calculated on a number of volumes of interest (VOI) are examined. We performed the data reduction techniques of principal components analysis (PCA) and partial least-squares (PLS) on the entire image and then used linear discriminant analysis (LDA), quadratic (QDA) or logistic regression (LR) to classify subjects as having AD or FTD. Some of these methods achieve diagnostic accuracy (as assessed by leave-one-out cross-validation) that is similar to visual ratings by expert raters. Methods using PLS appear to be more successful. Averaging or using VOI data may also be helpful., (Copyright 2004 John Wiley & Sons, Ltd.)

Lewy bodies were originally described in isolated brainstem nuclei in persons with Parkinson's disease. They have since been recognized as a widespread and common neuropathologic finding in individuals with dementia. Dementia with Lewy bodies (DLB) is the preferred term for the dementia syndrome associated with Lewy bodies. Although DLB is acknowledged as the second most common degenerative dementia, trailing only Alzheimer's disease, its ranking with respect to vascular dementia remains controversial. Large, community-based studies of DLB with postmortem confirmation are lacking. Available data suggest that DLB is more common than pure vascular dementia but not more common than any vascular contribution to dementia.

Background: Some elderly individuals exhibit significant memory deficits but do not have dementia because their general intellect is preserved and they have no impairments in everyday activities. These symptoms are often a precursor to Alzheimer disease (AD), but sometimes dementia does not occur, even after many years of observation. There is currently no reliable way to distinguish between these 2 possible outcomes in an individual patient. We hypothesized that clear impairments in at least 1 cognitive domain in addition to memory would help identify those who will progress to AD., Objective: To determine whether nondemented patients with impairments in memory and other domains are more likely than those with memory impairment alone to develop AD., Design and Methods: In a retrospective study, we evaluated 48 nondemented, nondepressed patients with clinical and psychometric evidence of memory impairment who were followed up for 2 or more years. Age-adjusted normative criteria were used to identify whether additional impairments were present in language, attention, motor visuospatial function, and verbal fluency at this initial evaluation. The presence or absence of dementia after 2 years and at the most recent neurological evaluation was compared in subjects with normal scores in all 4 of these cognitive areas apart from memory (M-) and those with impairment in 1 or more of these areas (M+). Outcomes were adjusted for age, intelligence at initial evaluation, and years of education., Results: Of the 48 nondemented patients with memory loss, 17 met M- criteria, leaving 31 in the M+ group. Deficits in block design were the most frequent abnormality other than memory loss. At the 2-year follow-up, 1 M- subject (6%) had progressed to AD, whereas 15 (48%) of the M+ group had progressed to AD (P =.003). At the most recent follow-up (mean +/- SD, 4.0 +/- 2.0 years), 4 (24%) of the M- patients progressed to AD compared with 24 (77%) of the M+ patients (P<.001)., Conclusions: Among nondemented elderly patients, memory loss alone rarely progresses to dementia in the subsequent 2 years. However, the risk of dementia is significantly increased among patients with clear cognitive impairments beyond memory loss. Further study is needed to determine whether patients with impairments limited to memory loss have a distinctive clinical course or pathophysiology.