Visual rating and volumetric measurement of medial temporal atrophy in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort: baseline diagnosis and the prediction of MCI outcome.

Objective: This study aims to determine the clinical utility of visual ratings and volumetric measurements of medial temporal atrophy among subjects from the Alzheimer's Disease Neurorimaging Initiative (ADNI) cohort.

Methods: A sample of 189 subjects from the ADNI, Phase 1 (ADNI-1), was chosen as follows: 49 cognitively normal (CN), 89 with mild cognitive impairment (MCI), and 50 with Alzheimer's disease (AD). Structural MRI images were downloaded from the ADNI website, and a visual rating system (VRS) was used to obtain semi-quantitative ratings of the hippocampus (HPC) and entorhinal cortex (ERC).

Significance of normalization on anatomical MRI measures in predicting Alzheimer's disease.

This study establishes a new approach for combining neuroimaging and neuropsychological measures for an optimal decisional space to classify subjects with Alzheimer's disease (AD). This approach relies on a multivariate feature selection method with different MRI normalization techniques. Subcortical volume, cortical thickness, and surface area measures are obtained using MRIs from 189 participants (129 normal controls and 60 AD patients).

The utility of age-specific cut-offs for visual rating of medial temporal atrophy in classifying Alzheimer's disease, MCI and cognitively normal elderly subjects.

Background: New research criteria for diagnosing Alzheimer's disease (AD) in the mild cognitive impairment stage (MCI-AD) incorporate biomarkers to assign a level of certainty to the diagnosis. Structural MRI is widely available but greatly under-utilized for assessing atrophy of structures affected in early AD, such as the hippocampus (HP), because the quantification of HP volumes (HP-v) requires special expertise, and normative values have not been established.

Methods: Elderly subjects (n =273) from the Florida ADRC were classified as having no cognitive impairment (cognitively normal, CN), amnestic mild cognitive impairment (aMCI) or AD.

An evaluation of deficits in semantic cueing and proactive and retroactive interference as early features of Alzheimer's disease.

Objectives: To determine the degree to which susceptibility to different types of semantic interference may reflect the initial manifestations of early Alzheimer's disease (AD) beyond the effects of global memory impairment.

Methods: Normal elderly (NE) subjects (n = 47), subjects with amnestic mild cognitive impairment (aMCI; n = 34), and subjects with probable AD (n = 40) were evaluated by using a unique cued recall paradigm that allowed for evaluation of both proactive and retroactive interference effects while controlling for global memory impairment (i.e.

Amyloid positron emission tomography with (18)F-flutemetamol and structural magnetic resonance imaging in the classification of mild cognitive impairment and Alzheimer's disease.

Objective: To evaluate the contributions of amyloid-positive (Am+) and medial temporal atrophy-positive (MTA+) scans to the diagnostic classification of prodromal and probable Alzheimer's disease (AD).

Methods: (18)F-flutemetamol-labeled amyloid positron emission tomography (PET) and magnetic resonance imaging (MRI) were used to classify 10 young normal, 15 elderly normal, 20 amnestic mild cognitive impairment (aMCI), and 27 AD subjects. MTA+ status was determined using a cut point derived from a previous study, and Am+ status was determined using a conservative and liberal cut point.

Comparing new templates and atlas-based segmentations in the volumetric analysis of brain magnetic resonance images for diagnosing Alzheimer's disease.

Background: The segmentation of brain structures on magnetic resonance imaging scans for calculating regional brain volumes, using automated anatomic labeling, requires the use of both brain atlases and templates (template sets). This study aims to improve the accuracy of volumetric analysis of hippocampus (HP) and amygdala (AMG) in the assessment of early Alzheimer's disease (AD) by developing template sets that correspond more closely to the brains of elderly individuals.

Methods: Total intracranial volume and HP and AMG volumes were calculated for elderly subjects with no cognitive impairment (n = 103), with amnestic mild cognitive impairment (n = 68), or with probable AD (n = 46) using the following: (1) a template set consisting of a standard atlas (atlas S), drawn on a young adult male brain, and the widely used Montreal Neurological Institute template (MNI template set); (2) a template set (template S set) in which the template is based on smoothing the image from which atlas S is derived; and (3) a new template set (template E set) in which the template is based on an atlas (atlas E) created from the brain of an elderly individual.

Cognitive and structural magnetic resonance imaging features of Lewy body dementia and Alzheimer's disease.

Objective: To assess medial temporal atrophy (MTA) and atrophy adjacent to the third ventricle (Peri-IIIVent) on brain magnetic resonance images as biomarkers for the diagnosis of Alzheimer's disease (AD) and Lewy body dementia (LBD), and to assess the relationship between biomarkers and clinical and functional measures.

Methods: Subjects diagnosed with no cognitive impairment (n = 30), AD (n = 30), or LBD (n = 31) were evaluated with the Mini-Mental State Examination, Multiple Delayed Recall Test, Category Fluency Test, Clinical Dementia Rating Sum of Boxes score, Functional Assessment Questionnaire, and the Unified Parkinson's Disease Rating Scale. A validated visual rating system was used to rate MTA, and volumetric studies were performed to measure total intracranial and hippocampal volumes.

An investigation of PreMCI: subtypes and longitudinal outcomes.

Background/aims: To investigate the clinical features and rates of progression of conditions that are not considered to be normal, but do not fulfill criteria for mild cognitive impairment (MCI).

Methods: We longitudinally evaluated 269 elderly subjects who did not meet formal criteria for MCI at baseline but had: (1) a clinical history suggesting MCI without neuropsychological deficits (PreMCI-Clinical); or (2) neuropsychological deficits on one or more memory measures in conjunction with a negative clinical examination (amnestic PreMCI-NP) or were normal on both neuropsychological and clinical examination.

Results: The rate of progression to MCI or dementia over an average of 2- to 3 years was 3.

Volumetric and visual rating of magnetic resonance imaging scans in the diagnosis of amnestic mild cognitive impairment and Alzheimer's disease.

Background: In the diagnosis of Alzheimer's disease (AD), structural magnetic resonance imaging (MRI) scans have been used primarily to exclude non-Alzheimer's causes of dementia. However, the pattern and the extent of medial temporal atrophy on structural MRI scans, which correlate strongly with the pathological severity of AD, can be used to support the diagnosis of a degenerative dementia, especially AD, even in its early predementia stage.

Methods: Elderly subjects (n = 224) were diagnosed with either no cognitive impairment (NCI), amnestic mild cognitive impairment (aMCI), or AD.

Minimal atrophy of the entorhinal cortex and hippocampus: progression of cognitive impairment.

Background: In Alzheimer's disease, neurodegenerative atrophy progresses from the entorhinal cortex (ERC) to the hippocampus (HP), limbic system and neocortex. The significance of very mild atrophy of the ERC and HP on MRI scans among elderly subjects is unknown.

Methods: A validated visual rating system on coronal MRI scans was used to identify no atrophy of the HP or ERC (HP(0); ERC(0)), or minimal atrophy of the HP or ERC (HP(ma); ERC(ma)), among 414 participants.

Pre-MCI and MCI: neuropsychological, clinical, and imaging features and progression rates.

Objective: To compare clinical, imaging, and neuropsychological characteristics and longitudinal course of subjects with pre-mild cognitive impairment (pre-MCI), who exhibit features of MCI on clinical examination but lack impairment on neuropsychological examination, to subjects with no cognitive impairment (NCI), nonamnestic MCI (naMCI), amnestic MCI (aMCI), and mild dementia.

Methods: For 369 subjects, clinical dementia rating sum of boxes (CDR-SB), ApoE genotyping, cardiovascular risk factors, parkinsonism (UPDRS) scores, structural brain MRIs, and neuropsychological testing were obtained at baseline, whereas 275 of these subjects received an annual follow-up for 2-3 years.

Results: At baseline, pre-MCI subjects showed impairment on tests of executive function and language, higher apathy scores, and lower left hippocampal volumes (HPCV) in comparison to NCI subjects.

Reliability and validity of an algorithm for the diagnosis of normal cognition, mild cognitive impairment, and dementia: implications for multicenter research studies.

Background: The traditional consensus diagnosis (ConsDx) of normal cognition, mild cognitive impairment (MCI), and dementia relies on the reconciliation of an informant-based report of cognitive and functional impairment by a physician diagnosis (PhyDx), and a neuropsychological diagnosis (NPDx). As this procedure may be labor intensive and influenced by the philosophy and biases of a clinician, the diagnostic algorithm (AlgDx) was developed to identify individuals as cognitively normal, with MCI, or dementia.

Methods: The AlgDx combines the PhyDx with the NPDx, using a diagnostic algorithm that provides cognitive diagnoses, as defined by the National Alzheimer Coordinating Center/Uniform Data Set nomenclature.

Severity of medial temporal atrophy and amnestic mild cognitive impairment: selecting type and number of memory tests.

Objective: Medial temporal lobe atrophy (MTA) can be used as a biomarker of pathology that affects mechanisms of episodic memory. The authors compared the strength of this biomarker with performance on four memory measures and examined the influence of demographic factors including age, level of education, and primary language (English or Spanish).

Methods: The Hopkins Verbal Learning Test-revised, Fuld Object Memory Evaluation (FOME), delayed memory for a story passage, and delayed visual reproduction of the Wechsler Memory Scale-revised tests were administered to 281 subjects who were diagnosed as having no cognitive impairment, mild cognitive impairment (MCI), impaired non-MCI, or dementia.

A comparative analysis of structural brain MRI in the diagnosis of Alzheimer's disease.

Dementia is a debilitating and life-altering disease which leads to both memory impairment and decline of normal executive functioning. While causes of dementia are numerous and varied, the leading cause among patients 60 years and older is Alzheimer's disease. The gold standard for Alzheimer's diagnosis remains histological identification of amyloid plaques and neurofibrillary tangles within the medial temporal lobe, more specifically the entorhinal cortex and hippocampus.

Diagnosis and staging of mild cognitive impairment, using a modification of the clinical dementia rating scale: the mCDR.

Objective: To examine the reliability and validity of the mCDR, a modified version of the clinical dementia rating (CDR) scale.

Methods: The mCDR is an informant-based, technician-administered, structured interview with multiple choice responses, which does not include objective cognitive testing. Subjects (n = 556) with no cognitive impairment (NCI), amnestic mild cognitive impairment (aMCI), and dementia were assessed with mCDR, CDR, and neuropsychological evaluation, while medial temporal atrophy (MTA) was measured on MRI scans.

The basis for disease-modifying treatments for Alzheimer's disease: the Sixth Annual Mild Cognitive Impairment Symposium.

At the Sixth Annual Mild Cognitive Impairment Symposium in Miami Beach, Florida, a multidisciplinary group of experts from the Alzheimer's disease (AD) community met to discuss the current status of AD intervention trials and future plans for designing trials of prodromal AD and/or mild cognitive impairment. There is no agreement regarding a single pathogenic mechanism to be targeted, although a consensus seems to be emerging that effective treatment will require attacking multiple targets. These targets include beta amyloid (Ass) aggregates (including different isoforms and different aggregation species), neurofibrillary tangles composed of hyperphosphorylated tau, neuronal and synaptic loss, and mechanisms that contribute to Ass deposition-induced inflammation and immune dysregulation.

Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease.

Background: Despite convenience, accessibility, and strong correlation to severity of Alzheimer disease (AD) pathology, medial temporal lobe atrophy (MTA) has not been used as a criterion in the diagnosis of prodromal and probable AD.

Methods: Using a newly validated visual rating system, mean MTA scores of three bilateral medial temporal lobe structures were compared for subjects with no cognitive impairment (NCI) (n = 117), nonamnestic mild cognitive impairment (MCI) (n = 46), amnestic MCI (n = 45), and probable AD (n = 53). Correlations between MTA scores and neuropsychological test scores at baseline, and predictors of change in diagnosis at 1-year follow-up were evaluated.

Towards an earlier diagnosis of Alzheimer disease (Proceedings of the 5th MCI Symposium, 2007).

The 5th annual Mild Cognitive Impairment Symposium, held on April 13th and 14th, 2007, in Miami Beach, Florida, focused on the question of whether the time has come to revise criteria for Alzheimer disease (AD). The symposium, sponsored by the Wien Center for Alzheimer's Disease and Memory Disorders, Mt Sinai Medical Center in Miami Beach, Florida; and the Byrd Alzheimer Center and Research Institute in Tampa, Florida, brought together an international group of clinicians and researchers to examine current evidence for developing new criteria for AD and for outlining areas that still require clarification. Neuropathologic, neuroimaging, epidemiologic, and clinical perspectives were presented and discussed, as well as the impact of ethnic and cultural differences.

Nonpharmacological cognitive interventions in aging and dementia.

There have been increasing efforts to develop cognitive interventions to ameliorate cognitive problems experienced by older adults. In healthy elderly populations, cognitive training has centered on the enhancement of memory and speed of processing, with the goal of maximizing current function and reducing the risk of cognitive decline. Among elderly persons with nonprogressive neurological conditions such as traumatic brain injury (TBI) and stroke, there has been an emphasis on rehabilitation to help restore function.

The use of amnestic and nonamnestic composite measures at different thresholds in the neuropsychological diagnosis of MCI.

Both amnestic and nonamnestic deficits have been observed in patients with mild cognitive impairment (MCI). Most studies have focused on impairment on single cognitive tests rather than amalgamation of the results of several measures to arrive at a composite impairment index. In this investigation, we examined 20 MCI patients diagnosed as prodromal Alzheimer's disease, AD (mean Mini-Mental State Examination, MMSE = 26.

Stability of neurocognitive impairment in different subtypes of mild cognitive impairment.

There has been increasing interest in delineating different cognitive subtypes of mild cognitive impairment (MCI). It remains unclear, however, the extent to which neuropsychological impairment associated with amnestic, nonamnestic, and amnestic+ subtypes of MCI remains stable over time. In this study, 70 persons meeting the criteria for MCI and 38 cognitively normal elderly subjects received a baseline neuropsychological evaluation and were reevaluated 1 year later.

Using different memory cutoffs to assess mild cognitive impairment.

Objective: Although mild cognitive impairment (MCI) is characterized by performance on memory and other measures below expected normative values, neither a scientific rationale nor a consensus exists regarding which measures have the most use or the optimal cutoffs to use to establish impairment.

Methods: Different memory measures were administered to 80 normal community-dwelling subjects divided into two age groups. This provided conormed data on eight different memory indices by which to compare 23 nondemented clinically diagnosed patients with MCI who met all other criteria for Alzheimer disease (AD).

A clinical perspective of mild cognitive impairment: what radiologists should know.

Mild cognitive impairment (MCI), a major risk factor for dementia, has an amnestic subtype that has a high probability of progressing to Alzheimer's disease. The rate of progression may be predicted by the severity of memory impairment at baseline, the severity of hippocampal atrophy, and, possibly, the presence of an epsilon4 allele of the apolipoprotein E gene. MCI can be diagnosed using purely clinical or a combination of clinical and neuropsychologic criteria.

The effect of a memory screening program on the early diagnosis of Alzheimer disease.

Context: Alzheimer Disease (AD) is often diagnosed at a moderately advanced stage, even though its early detection has become increasingly important, because of the continuing development of treatments that may improve its outcome.

Objective: To determine if a free memory screening program is associated with an earlier diagnosis of AD, compared with traditional referral methods, such as by physicians and family members.

Design, Setting, And Participants: A retrospective study of 1489 consecutive patients with AD who presented to an outpatient memory disorders clinic between 1993 and 2002.