Diagnostic Criteria For Alzheimer Research Articles

Evaluating the Performance of Different Criteria in Diagnosing AD and Preclinical AD with the Bayesian Latent Class Model.

The diagnostic criteria for Alzheimer's disease (AD) should be highly sensitive and specific. Clinicians have varying opinions on the different criteria, including the International Working Group-1 (IWG-1), International Working Group-2 (IWG-2), and AT(N) criteria. Few studies had evaluated the performance of these criteria in diagnosing AD and preclinical AD when the gold standard was absent. We estimated and compared the performance of these criteria in diagnosing AD using data from 908 subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Additionally, 622 subjects were selected to evaluate and compare the performance of IWG-2 and AT(N) criteria in diagnosing preclinical AD. A novel approach, Bayesian latent class models with fixed effect dependent, was utilized to estimate the diagnostic accuracy of these criteria in detecting different AD statuses simultaneously. The sensitivity of the IWG-1, IWG-2, and AT(N) criteria in diagnosing AD was 0.850, 0.836, and 0.665. The specificity of these criteria was 0.788, 0.746, and 0.747. The IWG-1 criteria had the highest Youden Index in detecting AD. When diagnosing preclinical AD, the sensitivity of the IWG-2 and AT(N) criteria was 0.797 and 0.955. The specificity of these criteria was 0.922 and 0.720. The IWG-2 criteria had the highest Youden Index. IWG-1 was more suitable than the IWG-2 and AT(N) criteria in detecting AD. IWG-2 criteria was more suitable than AT(N) criteria in detecting preclinical AD.

The effects of low-dose radiation therapy in patients with mild-to-moderate Alzheimer's dementia: an interim analysis of a pilot study.

We aimed to determine whether low-dose radiotherapy (LDRT) is effective in patients with Alzheimer disease (AD). We included patients according to the following criteria: probable Alzheimer's dementia according to the New Diagnostic Criteria for Alzheimer's Disease; confirmation of amyloid plaque deposits on baseline amyloid positron emission tomography (PET); a Korean Mini-Mental State Examination 2nd edition (K-MMSE-2) score of 13-26; and a Global Clinical Dementia Rating (CDR) score of 0.5-2 points. LDRT was performed six times at 0.5 Gy each. Post-treatment cognitive function tests and PET-CT examinations were performed to evaluate efficacy. The medication for AD treatment was maintained throughout the study period. At 6 months after LDRT, neurological improvement was seen in 20% of patients. Patient #2 showed improvement in all domains of the Seoul Neuropsychological Screening Battery II (SNSB-II). Moreover, the K-MMSE-2 and Geriatric Depression Score-Short Form scores improved from 20 to 23 and from 8 to 2, respectively. For patient #3, the CDR score (sum of box score) improved from 1 (4.0) to 1 (3.5) at 3 months follow-up. Moreover, the Z scores for language and related functions, memory, and frontal executive function improved to -2.56, -1.86, and -1.32, respectively at the 6-month follow-up. Two patients complained of mild nausea and mild hair loss during LDRT, which improved after treatment. One of the five patients with AD treated with LDRT experienced a temporary improvement in SNSB-II. LDRT is tolerable in patients with AD. We are currently under follow-up and will conduct cognitive function tests after 12 months after LDRT. A large-scale randomized controlled trial with a longer follow-up period is warranted to determine the effect of LDRT on patients with AD.

Alzheimer's Disease is a Disorder of Consciousness.

The diagnostic criteria for Alzheimer's disease (AD) described in DSM-5-TR, require a decline in memory and learning and in at least one other cognitive domain among six cognitive domains, and also interference with the activities of daily living (ADL) because of decline in these cognitive functions; as such, DSM-5-TR positions memory impairment as the core symptom of AD. DSM-5-TR shows the following examples of symptoms or observations regarding impairments in everyday activities in terms of learning and memory involving the six cognitive domains. Mild: Has difficulty recalling recent events, and relies increasingly on list making or calendar. Major: Repeats self in conversation, often within the same conversation. These examples of symptoms/observations demonstrate difficulties in recall, or difficulties in bringing memories into the consciousness. In the article, it is proposed that considering AD as a disorder of consciousness could promote a better understanding of the symptoms experienced by AD patients and contribute to devising methods to provide improved care to these patients.

Brief risk rating scale: A preliminary screening and monitoring tool emphasizing individual differences for better prognosis in Alzheimer’s disease

Over the last several decades, significant progress has been made in the diagnostic criteria of Alzheimer’s disease (AD) to identify its early stages, including subjective cognitive decline and mild cognitive impairment. However, the previous research rarely took account of individual differences when evaluating AD-spectrum patients at different stages, thereby resulting in similar treatment, which was not only ineffective but also resulted in the missed window of opportunity for intervention. In this review, we propose the Brief Risk Rating Scale (BRRS), which is predominantly based on extant literature concerning AD risk factors and brain alterations, with the aim of providing a preliminary screening and monitoring tool that can facilitate the assessment of individual’s risk level, the prediction and tracking of disease progression, as well as precise treatment in a timely manner. Meanwhile, due to its simplicity and ease of use, it can be widely promoted and likewise accessible to clinicians in grassroots clinics. In general, the scale comprises two parts: The original score (O) related to patients’ risk factors and the variation score (V) related to brain abnormalities tested by different sequences of magnetic resonance imaging. In addition, the advantages along with its clinical application, such as introducing BRRS into cognitive training and brain stimulation, are also discussed. We conclude that BRRS positively contributes to enhancing the accuracy of clinical diagnosis and the efficiency of personalized treatment in AD-spectrum patients, with individual differences fully considered and little additional burden added. However, the weight coefficient of each item in BRRS should be thoroughly studied in future research.

Diagnosis of Alzheimer's disease: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer's disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research.

Diagnóstico da doença de Alzheimer: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

ABSTRACT This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer’s disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research.

The amnestic syndrome of hippocampal type is frequent in patients without hippocampal atrophy in a memory clinic population

AbstractBackgroundSince 2011, diagnostic criteria for Alzheimer’s Disease have led to the introduction of biomarkers. Hippocampal atrophy, either volumetric or visually‐rated is arguably the most widely available biomarker of neurodegeneration. An association with a specific type of amnestic disorder has been claimed, but the clinical validity of this concept remains to be established in unselected patient populations. This problem is important as the amnestic syndrome of the hippocampal type is theoretically a key element in the diagnosis of the most common clinical syndrome of Alzheimer’s disease. Our objective was to determine the correlation between the amnestic syndrome of hippocampal type and hippocampal atrophy.MethodThis is a retrospective study of 274 consecutive patients who were assessed in the Memory Clinic between 01/2014 and 11/2018. Verbal memory was assessed with the Free and Cued Selective Reminding Test (FCSRT) and the Montreal Cognitive Assessment Memory Index Score. Brain imaging was performed within six months of the neuropsycholgical assessment and hippocampal atrophy was estimated using the Scheltens Scale, adjusted for age.ResultThe Scheltens scale had a moderate correlation with FCSRT free recall (Pearson correlation = ‐0,425, p<0,001) and weak correlation with FCSRT Cueing index (Pearson correlation = ‐ 0,293, p< 0,001). However, 34% of our cohort (n=93) had an abnormal FCSRT Cueing index (< = 71%), but a normal Scheltens score. As for the MoCA‐MIS, 26% of our cohort (n=57) had an abnormal score (< = 7), but a normal Scheltens score.ConclusionA large subgroup of our patients demonstrate an amnestic syndrome of the hippocampal type, without showing hippocampal atrophy on routine brain imaging. Our results show the limits of equating hippocampal atrophy with the particular profile of amnesia that does not improve with cueing. The claimed specificity of this type of cognitive deficit in the differential diagnosis of dementia needs to be re‐assessed.

Research diagnostic criteria for Alzheimer’s disease: Findings from the multinational LipiDiDiet Trial

AbstractBackgroundLipiDiDiet is a randomized controlled trial investigating the effects of a multinutrient medical food product on change in cognition among individuals with prodromal AD. This study aimed at investigating participants’ baseline AD biomarker profile, including classification according to the IWG‐2 and NIA‐AA 2011 & 2018 diagnostic criteria, and assessing the impact on 2‐year cognitive/functional decline and progression to dementia.MethodLipiDiDiet targeted 311 individuals aged 55–85 years at 11 sites in four countries. Prodromal AD was defined according to the IWG‐1 criteria: evidence for AD pathology (abnormality in any CSF or imaging biomarker) and episodic memory impairment. Key outcomes were e.g. change in cognition and function (Neuropsychological Test Battery NTB z‐scores, CDR‐SB) and progression to dementia. Linear mixed models were used to investigate change in NTB and CDR‐SB scores across different baseline biomarker profiles (biomarker profile x time interactions). Associations between biomarker profiles and risk of progression to dementia were analyzed with Cox proportional hazards models adjusted for randomization group, MMSE, and study site.ResultCSF Aβ, t‐tau, and p‐tau levels were abnormal in 88%, 86%, and 69% of participants with centrally assessed CSF (N=107). 64% had an A+/T+/N+ profile. While cognitive/functional decline tended to be more pronounced in the IWG‐2 prodromal AD, NIA‐AA 2011 high and intermediate AD likelihood, and NIA‐AA 2018 AD groups, few statistically significant differences were observed between diagnostic groups within each set of criteria. Hazard ratio (95% CI) for progression to dementia was 4.7 (1.6–13.7) among participants with IWG‐2 prodromal AD (compared with no prodromal AD); 7.5 (1.0–55.0) for NIA‐AA 2011 high AD likelihood group (compared with SNAP), and 9.4 (1.2–72.7) for NIA‐AA 2018 AD group (compared with non‐Alzheimer’s pathologic change).ConclusionDespite being less restrictive than the more recent diagnostic criteria, IWG‐1 criteria reliably identified individuals with AD pathology. Findings may have implications for future trial design, as these criteria may be preferred due to feasibility in trials conducted in diverse settings, e.g. clinical trials which do not directly target Aβ or tau pathology.

Recovery of Dementia Syndrome following Treatment of Brain Inflammation

Aim/Background: This research aims to prevent progression from mild cognitive impairment (MCI) to Alzheimer’s disease. A Japanese study of leprosy patients revealed that the incidence of dementia in leprosy patients was lower than that in patients taking dapsone who had never been treated. But a similar study the following year refuted the finding of less dementia in leprosy patients taking dapsone. According to conflicting reports, Mycobacterium leprae was a factor in reducing the incidence of Alzheimer’s disease. Thus, we formed a hypothesis that if dapsone is administered to patients without leprosy but with MCI and the prophylactic effect of dementia syndrome is observed over a long period of time, we can determine whether dapsone can prevent the progression of MCI to dementia syndrome. If dementia does not occur after treating inflammation in brain cells while dementia develops after a certain long-term period (usually within 2–3 years), brain cell inflammation can be demonstrated as the cause of dementia. Methods: This is a prospective cohort research. We report on an elderly patient diagnosed with MCI from February 2008 to January 2019. The patient took dapsone 100 mg once a day from 2010 to 2015 for the treatment of MCI. Since 2016, the production of dapsone has ceased in Korea. In June 2018, the patient was diagnosed with Alzheimer’s disease. The patient took Aricept for the treatment of Alzheimer’s disease but complained of serious side effects. And dapsone was re-administered to the patient from November 2018. Results: The patient recovered to MCI and improved her daily life owing to the treatment with dapsone. The drug controls the inflammatory response in the brain, irrespective of whether proteins are deposited in neurons. Conclusions:This finding means that dementia syndrome is an inflammatory disease. This research suggests that diagnostic criteria for Alzheimer’s disease should be based on the presence or absence of inflammation in neurons. Because inflammation in neurons can occur in middle age due to various causes, we can treat inflammation in neurons and prevent and treat dementia syndrome, including Alzheimer’s disease.

O-40 EEGmine : EEG as a prognosis tool of cognitive decline in routine clinical practice

Over the last years, different efforts were made for the early prediction of cognitive worsening in different neurodegenerative diseases. EEG was widely highlighted as a potentially clinically suitable exploration modality for this purpose. Specific EEG abnormalities have been reported in different pathologies and mainly for the discrimination of mild cognitive patients from demented patients, as a general reduction of power in the alpha and beta bands and high power of widespread delta and theta rhythms in the latter group. However, findings were mainly limited for groups and population description without reaching the patient individual diagnosis. This study aims to investigate EEG rhythms alterations in a large population formed by patients complaining of cognitive distress followed in the Lille Memory Center and diagnosed according to the newest diagnostic criteria of Alzheimer’s Disease, Lewy Body disease, cerebrovascular dementia and mild cognitive impairments. Data including standard 19 electrodes resting-state closed eyes EEG, acquired in the clinical neurophysiological department and clinical evaluations including cognitive status by means of MMSE score and neuropsychological assessment, were collected from 320 patients. EEG from 300 other patients, matched in term of sex and age with the first patients’ group were also considered. These patients were explored in EEG for non-cognitive indications and thus considered as a control group. Different EEG analysis are considered as: visual assessment, quantitative analysis in the common frequency bands and connectivity. For the two last approaches, machine learning algorithms are investigated to build patients individual classification models.

Frontal variant of Alzheimer’s disease masquerading as behavioural-variant frontotemporal dementia: a case study comparison

ABSTRACTThe current clinical diagnostic criteria for Alzheimer’s disease (AD) recognize an atypical, non-amnestic presentation of AD, characterized by prominent executive dysfunction. Increasing evidence, however, indicates that the clinical phenotype of this so-called “frontal-variant” of AD (fv-AD) includes behavioral symptoms and deficits in social cognition, together with disproportionate frontal lobe atrophy. As these features resemble those characteristic of behavioral-variant frontotemporal dementia (bvFTD), differential diagnosis can be challenging. Here, we report a case of fv-AD who met clinical diagnostic criteria bvFTD, but had in vivo amyloid neuroimaging evidence of AD pathology. We compare this case against two individuals who were clinically diagnosed with bvFTD and early-onset AD, with in vivo amyloid neuroimaging confirmation of pathology. We highlight the challenges in differential diagnosis by contrasting their behavioral, cognitive and structural neuroimaging findings.

Reappraisal of Aβ40 and Aβ42 Peptides Measurements in Cerebrospinal Fluid of Patients with Alzheimer's Disease.

Cerebrospinal fluid (CSF) biomarkers are currently included in the diagnostic criteria for Alzheimer's disease (AD), in particular, decreased concentrations of amyloid-β peptide 1-42 (Aβ42) in the CSF, coupled with increased levels of tau and phosphorylated tau proteins, are supportive of AD diagnosis. To date, the quantification of Aβ42 levels with antibody-dependent immunoassay shows a marked variability among different laboratories and is also affected by different pre-analytical factors, suggesting that part of Aβ42 peptides might be aggregated and thus undetected by antibodies. To bypass an antibody-dependent measurement, we determined the Aβ40 and Aβ42 levels by immunoblot. We analyzed CSF samples from 35 patients with clinical diagnosis of probable AD and from 15 age-matched normal controls; CSF Aβ levels were determined by two different ELISA kits and by immunoblot analysis. Aβ40 levels measured by ELISA were comparable to those obtained by immunoblot, whereas CSF concentrations of Aβ42 measured by ELISA were significantly lower compared to values obtained by immunoblot quantification. Biochemical analysis, following 1D- and 2D-PAGE analysis, showed that the qualitative composition of Aβ peptides in the CSF is similar in AD and controls but different from that of AD brain tissues. Moreover, sedimentation velocity in sucrose gradient of CSF and brain homogenate from AD demonstrated that Aβ42 in CSF is different from Aβ42 in brain in terms of solubility and aggregation state.

The application of lipidomics to biomarker research and pathomechanisms in Alzheimer's disease.

Alzheimer's disease is the most common cause of dementia. There are still no disease modifying treatments that can cure or slow disease progression. Recently, Alzheimer's disease researchers have attempted to improve early detection and diagnostic criteria for Alzheimer's disease, with the rationale that treatment of disease, or even prevention, may be more successful during the early preclinical stages of Alzheimer's disease when neurodegenerative damage is not as widespread. As the brain has a high lipid content, lipidomics may offer novel insights into the underlying pathogenesis of Alzheimer's disease. This review reports on recent developments in the relatively unexplored field of lipidomics in Alzheimer's disease, including novel biomarkers and pathomechanisms of Alzheimer's disease. Numerous biomarker panels involving phospholipids and sphingolipids have been proposed, indicating perturbed lipid metabolism in early stages of Alzheimer's disease. Future strategies targeting these metabolic changes through dietary supplementation could have therapeutic benefits in at-risk individuals. Dysregulated lipid metabolism could reflect pathological changes in synaptic function and neuronal membranes, leading to cognitive decline. However, extensive validation in large independent cohorts is required before lipid biomarkers can be used clinically to assess Alzheimer's disease risk and progression.

45. Skin nerve α-synuclein deposits as possible new biomarker for Dementia with Lewy bodies

The object of this study is to investigate whether: (1) phosphorylated α -synuclein (p-syn) deposits in peripheral nerves might represent a useful biomarker in dementia Lewy Body (DLB) helping to differentiate DLB from other forms of dementia; (2) small fiber neuropathy (SFN) may be part of DLB pathological picture contributing to autonomic dysfunctions. 20 well-characterized DLB patients (11 of them complaining autonomic symptoms particularly orthostatic hypotension) were studied together with 23 patients with dementia of different pathogenesis (Dementia without synuclein- DWS) including 13 patients fulfilling diagnostic criteria for Alzheimer’s disease, 6 with Frontotemporal Dementia and 4 with vascular dementia. Twenty-five age-matched healthy subjects served as controls. Subjects underwent: nerve conduction velocities from the leg to evaluate large nerve fibers; skin biopsy from proximal (i.e. cervical) and distal (i.e. thigh and distal leg) sites to study small nerve fibers and deposits of phosphorylated α -synuclein, considered the pathological form of α -synuclein. P-syn was not found in any skin sample in DWS patients and controls but it was found in all DLB patients with a proximal-distal gradient with all patients positive in the cervical site. Patients complaining of autonomic symptoms showed higher widespread positivity of analyzed skin samples than patients without autonomic symptoms. Furthermore DLB patients showed a length-dependent SFN particularly important in patients complaining autonomic symptoms. Conclusions: (1) p-syn in peripheral nerves is a sensitive biomarker for DLB diagnosis helping to differentiate DLB from other forms of dementia; (2) SFN was part of DLB pathological picture contributing to induce autonomic symptoms.

Amyloid tracers binding sites in autosomal dominant and sporadic Alzheimer's disease

IntroductionAmyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structures and amyloid-β aggregates in autosomal dominant AD (ADAD) and sporadic AD is unclear. MethodsBinding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1 EΔ9 mutations, 13 sporadic AD, and 14 control cases. Results3H-PIB, 3H-florbetaben, 3H-AZD2184, and BTA-1 shared a high- and a varying low-affinity binding site in the frontal cortex of sporadic AD. AZD2184 detected another binding site (affinity 33 nM) in the frontal cortex of ADAD. The 3H-AZD2184 and 3H-PIB binding were significantly higher in the striatum of ADAD compared to sporadic AD and control. Polyphenol resveratrol showed strongest inhibition on 3H-AZD84 binding followed by 3H-florbetaben and minimal on 3H-PIB. DiscussionThis study implies amyloid tracers of different structures detect different sites on amyloid-β fibrils or conformations.

Cerebrospinal fluid biomarkers in Alzheimer's and Parkinson's diseases-From pathophysiology to clinical practice.

This review provides an update on the role, development, and validation of CSF biomarkers in the diagnosis and prognosis of Alzheimer's disease and PD. Some recent developments on novel biomarkers are also discussed. We also give an overview of methodological/technical factors still hampering the global validation and standardization of CSF Alzheimer's disease and PD biomarkers. CSF biomarkers have the potential to improve the diagnostic accuracy at the early stages not only for Alzheimer's disease but also for PD. This step is essential in view of the availability of disease-modifying treatments. Our vision for the future is that analyzing biomarker panels on a minute amount of CSF could provide important information on the whole spectrum of the molecular pathogenic events characterizing these neurodegenerative disorders. CSF core biomarkers have already been included in the diagnostic criteria for Alzheimer's disease, and they are also under consideration as tools to monitor the effects of disease-modifying drugs. With respect to PD, their potential for improving diagnostic accuracy in early diagnosis is under intense research, resembling the same path followed for Alzheimer's disease. © 2016 International Parkinson and Movement Disorder Society.

Complex Treatment of the Patients with Alzheimer’s Disease Using Stem Cell Preparations Including Extracted Fetal Stem Cells

Objective: The principal aim of this study was to evaluate effectiveness of combined therapy method with inclusion of the standard protocol of treatment using medicines along with application of separated fetal stem cells (FSCs). Higher efficacy of treatment of the patients with Alzheimer’s Disease (AD) is defined as a technical value of our complex therapy. Material and Methods: We performed a comparative study of the groups of patients including women and men aged from 50 to 85 years who were presented with diagnostic criteria of Alzheimer’s type dementia by DSM- IV-TR, NINCDS-ADRDA as well as study of the patients with confirmed diagnosis of AD in accordance with ICD-10-CM suffering from mild and moderate-to-severe stages of dementia by CDR and MMSE scales. Along with standard treatment by use of stable doses of medicines our patients were administered FSCs suspensions containing stem cells extracted from the tissues of fetal liver and brain (human cadaveric fetuses of 7-12 weeks gestation) which were acquired as a result of medical abortion due to social and family planning reasons. Results: In a process of the comparative study the results we received emphasize treatment significance and advantages of complex therapy method compared to standard treatment used as isolated therapy for AD patients suffering from mild-to-moderate dementia. The suggested method of complex treatment is safe and contributes to improved cognitive functions as well as increased daily activities among such a group of AD patients (p<0.05). Conclusion: Use of preparations with extracted FSCs in complex treatment of the AD patients with mild and moderate grades of dementia has been proven to be safe and effective method of therapy which contributed to better cognitive functions and increased everyday activity among patients with AD.

Clinical and research value of the new diagnostic criteria for Alzheimer's disease.

SummaryThe use of biomarkers in the diagnosis of Alzheimer’s disease (AD) has been increasingly emphasized, but the feasibility and value of using biomarkers in clinical practice remain limited. However, the use of biomarkers in clinical and pharmaceutical research about AD may prove quite useful in clarifying the pathology underlying AD and, thus, help in the early identification of effective preventive and therapeutic interventions. Moreover, wide adoption of the new diagnostic criteria will improve comparability of research results across studies, and, thus, allow for the combination and comparison of study results using meta-analytic techniques – the types of analyses needed to definitively answer fundamental questions about the etiology, course, prevention, and treatment of AD.

Classification of non-demented patients attending a memory clinic using the new diagnostic criteria for Alzheimer's disease with disease-related biomarkers.

New diagnostic criteria for predemential Alzheimer's disease (AD) advocate the use of biomarkers. However, the benefit of using biomarkers has not been clearly demonstrated in clinical practice. To investigate whether a combination of biomarkers may be helpful in classifying a population of non-demented patients attending a Memory Clinic. Sixty non-demented patients were compared with 31 healthy elderly subjects. All subjects underwent a neuropsychological examination, brain 3T magnetic resonance imaging, [F18]-fluorodeoxyglucose and [F18]-flutemetamol positron emission tomography. According to their performance on memory, language, executive, and visuo-spatial domains, the patients were classified as mild cognitive impairment (amnestic, non-amnestic, single, or multiple domain) or subjective cognitive impairment. Patients were then classified according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, using the normalized mean hippocampal volume (Freesurfer), [F18]-FDG PALZAD, and [F18]-flutemetamol standard uptake value ratio (SUVr) (cut-off at the 10th percentile of controls). The standard of truth was the clinical status at study entry (patient versus control). The sensitivity/specificity of the clinical classification was 65/84%. The NIA-AA criteria were applicable in 85% of patients and 87% of controls. For biomarkers the best sensitivity (72%) at a fixed specificity of 84% was achieved by a combination of the three biomarkers. The clinical diagnosis was reconsidered in more than one third of the patients (42%) as a result of including the biomarker results. Application of the new NIA-AA AD diagnostic criteria based on biomarkers in an unselected sample of non-demented patients attending a Memory Clinic was useful in allowing for a better classification of the subjects.

(11)C-PIB-PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).

According to the latest revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (now known as the Alzheimer's Association) (NINCDS-ADRDA) diagnostic criteria for Alzheimer's disease dementia, the confidence in diagnosing mild cognitive impairment (MCI) due to Alzheimer's disease dementia is raised with the application of imaging biomarkers. These tests, added to core clinical criteria, might increase the sensitivity or specificity of a testing strategy. However, the accuracy of biomarkers in the diagnosis of Alzheimer's disease dementia and other dementias has not yet been systematically evaluated. A formal systematic evaluation of the sensitivity, specificity, and other properties of positron emission tomography (PET) imaging with the (11)C-labelled Pittsburgh Compound-B ((11)C-PIB) ligand was performed. To determine the diagnostic accuracy of the (11)C- PIB-PET scan for detecting participants with MCI at baseline who will clinically convert to Alzheimer's disease dementia or other forms of dementia over a period of time. The most recent search for this review was performed on 12 January 2013. We searched MEDLINE (OvidSP), EMBASE (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science and Conference Proceedings (ISI Web of Knowledge), PsycINFO (OvidSP), and LILACS (BIREME). We also requested a search of the Cochrane Register of Diagnostic Test Accuracy Studies (managed by the Cochrane Renal Group).No language or date restrictions were applied to the electronic searches and methodological filters were not used so as to maximise sensitivity. We selected studies that had prospectively defined cohorts with any accepted definition of MCI with baseline (11)C-PIB-PET scan. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis for example NINCDS-ADRDA or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. We screened all titles generated by electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies. The identified full papers were assessed for eligibility and data were extracted to create two by two tables. Two independent assessors performed quality assessment using the QUADAS 2 tool. We used the hierarchical summary receiver operating characteristic (ROC) model to produce a summary ROC curve. Conversion from MCI to Alzheimer's disease dementia was evaluated in nine studies. The quality of the evidence was limited. Of the 274 participants included in the meta-analysis, 112 developed Alzheimer's dementia. Based on the nine included studies, the median proportion converting was 34%. The studies varied markedly in how the PIB scans were done and interpreted.The sensitivities were between 83% and 100% while the specificities were between 46% and 88%. Because of the variation in thresholds and measures of (11)C-PIB amyloid retention, we did not calculate summary sensitivity and specificity. Although subject to considerable uncertainty, to illustrate the potential strengths and weaknesses of (11)C-PIB-PET scans we estimated from the fitted summary ROC curve that the sensitivity was 96% (95% confidence interval (CI) 87 to 99) at the included study median specificity of 58%. This equated to a positive likelihood ratio of 2.3 and a negative likelihood ratio of 0.07. Assuming a typical conversion rate of MCI to Alzheimer's dementia of 34%, for every 100 PIB scans one person with a negative scan would progress and 28 with a positive scan would not actually progress to Alzheimer's dementia.There were limited data for formal investigation of heterogeneity. We performed two sensitivity analyses to assess the influence of type of reference standard and the use of a pre-specified threshold. There was no effect on our findings. Although the good sensitivity achieved in some included studies is promising for the value of (11)C-PIB-PET, given the heterogeneity in the conduct and interpretation of the test and the lack of defined thresholds for determination of test positivity, we cannot recommend its routine use in clinical practice.(11)C-PIB-PET biomarker is a high cost investigation, therefore it is important to clearly demonstrate its accuracy and standardise the process of the (11)C-PIB diagnostic modality prior to it being widely used.