Anosognosia in Mild Cognitive Impairment: Lack of Awareness of Memory Difficulties Characterizes Prodromal Alzheimer's Disease

While anosognosia is often present in Alzheimer's disease, the degree of awareness of cognitive difficulties in the earlier stages, such as Mild Cognitive Impairment (MCI), is less clear. Using a questionnaire and Feeling-of-Knowing tasks, the aims of this study were (1) to test the hypothesis that anosognosia is present specifically in prodromal AD stage in patients that, owing to a more severe AD neuropathology, will rapidly progress to overt dementia and (2) to assess the neural bases of self-awareness for memory functioning. A group of 44 patients with amnestic MCI and a group of 29 healthy older participants (CTRL) performed two Feeling-of-Knowing tasks (episodic and semantic FOK) and responded to the Functional Memory Scale (MARS), also completed by one of their relatives. They underwent FDG-PET and structural MRI. The participants were followed clinically for 4 years. At the end of follow-up, 23 patients with MCI developed Alzheimer's disease (converters) and 21 patients still presented symptoms of MCI without progression (non-converters). The analyses focused on the data from inclusion stratified according to clinical status 4 years later (converters, non-converters, CTRL). On the episodic FOK task, converters patients overestimated their ability to later recognize unrecalled words and they showed prediction accuracy (Hamann coefficient) at the level of chance. No difficulty was observed in any group with the semantic FOK task. On the MARS, converters patients had a higher anosognosia score than non-converters patients and CTRL, which did not differ from each other. Correlations between self-awareness scores and neuroimaging data using small volume correction analyses in a priori regions of interest in converters indicated that inaccurate episodic FOK judgments was related to changes in brain areas that might support interpretation of retrieved content for judging the likelihood of recognition. For the MARS, the association between anosognosia and decreased gray matter density of the left inferior prefrontal cortex in converters might indicate poor inhibition over outdated personal knowledge. In amnestic MCI, anosognosia could be an early sign of neurodegeneration in brain areas that would support control mechanisms over memory representations.

Download Full-text

Elucidating the risk factors for progression from amyloid-negative amnestic mild cognitive impairment to dementia

Current Alzheimer Research ◽

10.2174/1567205017666201130094259 ◽

2020 ◽

Vol 17 ◽

Author(s):

Hyung-Ji Kim ◽

Jae-Hong Lee ◽

E-nae Cheong ◽

Sung-Eun Chung ◽

Sungyang Jo ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Amnestic Mild Cognitive Impairment ◽

Amyloid Pet ◽

Clinical Progression ◽

Amnestic Mci

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.

Download Full-text

Classifying Early and Late Mild Cognitive Impairment Stages of Alzheimer’s Disease by Analyzing Different Brain Areas

2020 Medical Technologies Congress (TIPTEKNO) ◽

10.1109/tiptekno50054.2020.9299217 ◽

2020 ◽

Author(s):

Gokce UYSAL ◽

Mahmut Ozturk

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Brain Areas

Download Full-text

Usefulness of CSF Biomarkers in Predicting the Progression of Amnesic and Nonamnesic Mild Cognitive Impairment to Alzheimer’s Disease

Current Aging Science ◽

10.2174/1874609812666190112095430 ◽

2019 ◽

Vol 12 (1) ◽

pp. 35-42

Author(s):

Ricard L. Ortega ◽

Farida Dakterzada ◽

Alfonso Arias ◽

Ester Blasco ◽

Alba Naudí ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Csf Biomarkers ◽

Prodromal Phase ◽

Diagnosis And Prognosis ◽

Amnestic Mci ◽

Atypical Presentations ◽

T Tau

Objective: The aim of this study was to investigate the usefulness of Alzheimer’s disease Cerebrospinal Fluid (CSF) biomarkers in predicting the progression to dementia in patients with Mild Cognitive Impairment (MCI). Methods: One hundred and thirteen patients were consecutively recruited from April 2012 to April 2014. Measurement of CSF biomarkers (amyloid-β42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau)) and a neuropsychological evaluation were performed for all patients. We categorized patients with MCI as A+A- and N+N- based on the presence/absence of amyloid pathology and neurodegeneration, respectively. Results: Of 72 patients with MCI, 26 (36%) progressed to dementia. These patients had lower CSF Aβ42 levels and higher p-tau and t-tau levels at baseline. The proportion that progressed to dementia was 14.3% (2/14), 36.8% (7/19), 66.7% (4/6) and 75% (12/16) in the A-N-, A+N-, A-N+ (SNAP), and A+N+ patients, respectively (p < 0.05). There were significant differences in the probability of progression from amnestic MCI (aMCI) to AD between the A+N+ and A-N- patients (OR = 8.1, 95% CI 1.5-42.3, p = 0.001) but not between SNAP (OR = 7.3, 95% CI 0.9-61, p = 0.02) or A+N- (OR = 2.1, 95% CI 0.4 to 10.4, p = 0.15) patients compared to the A-N- subgroup. None of the biomarker profiles of the subgroups predicted the time until the progression to AD. Conclusion: The use of CSF AD biomarkers in clinical practice improves the certainty of diagnosis and prognosis of patients, especially in patients in the prodromal phase or in patients with atypical presentations.

Download Full-text

New diagnostic concepts in Alzheimer's disease

Advances in Psychiatric Treatment ◽

10.1192/apt.bp.112.010462 ◽

2013 ◽

Vol 19 (4) ◽

pp. 242-249 ◽

Cited By ~ 2

Author(s):

Anna Watkin ◽

Sudip Sikdar ◽

Biswadeep Majumdar ◽

Anna V. Richman

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Clinical Practice ◽

Mild Cognitive Impairment ◽

Diagnostic Criteria ◽

Current Clinical Practice ◽

Amnestic Mci ◽

Recent Developments

SummaryThis article gives an overview of the profile of Alzheimer's disease, its pathophysiology and recent developments in technology that enable better understanding of the mechanism of disease. The diagnostic criteria and role of biomarkers proposed are explained. The new subgroups described are outlined in table form for easy reference. Subtypes of mild cognitive impairment (MCI) are reviewed and the conversion of amnestic MCI to Alzheimer's disease is considered. The implications and change to current clinical practice form the basis of the conclusion of the article.

Download Full-text

The Apathy Evaluation Scale (AES-C): Psychometric Properties and Invariance of Italian Version in Mild Cognitive Impairment and Alzheimer’s Disease

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18189597 ◽

2021 ◽

Vol 18 (18) ◽

pp. 9597

Author(s):

Giovanna Furneri ◽

Silvia Platania ◽

Alessandra Privitera ◽

Federica Martelli ◽

Rossana Smeriglio ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Psychometric Properties ◽

Prodromal Symptom ◽

General Factor ◽

Italian Version ◽

Amnestic Mci ◽

Experimental Group

Apathy is a neuropsychiatric symptom observed in different neurological and psychiatric disorders. Although apathy is considered a symptom, it has been recently reconsidered as a syndrome characterised by three dimensions: cognitive symptoms, affective symptoms and behavioural symptoms. Recent studies have shown that apathy can be considered as a prodromal symptom of Alzheimer’s disease (AD), but also an indicator of the transition from mild cognitive impairment to AD. According to this scenario, an early detection of apathy in subjects with Mild Cognitive Impairment (MCI) and Mild AD can be a valid psychometric strategy to improve an early diagnosis and promote a prompt intervention. The Apathy Evaluation Scale is a validated tool composed of 18 items that assess and quantify emotional, behavioural and cognitive aspects of apathy. The aim of this study is to assess the specific reliability and validity of the Italian version of the Apathy Evaluation Scale—Clinician Version (AES-C) to detect apathy both in amnestic MCI and mild AD patients. In the present paper, we therefore examined the psychometric properties and the invariance of the Italian Version of the AES-C conducted on a sample composed of an experimental group of amnestic MCI and AD patients (N = 107) and a control group (N = 107) constituted by Age- and Sex-matched healthy controls. Results confirm the goodness of the scale. Confirmatory factory analysis confirmed that the AES-C Italian Version presents the same stability of one second-order factor and three first-order factors identified in the original version, and all items are predicted by a single general factor. Moreover, the scale was found to be invariant across both populations. Moreover, reliability and discriminant analysis showed good values. We found in the experimental group a negative correlation between the AES-C and Frontal Assessment Battery (FAB) (rs = −0.21, p < 0.001) and Mini Mental State Examination (MMSE) (rs = −0.04, p < 0.001), while a positive correlation was found between the AES-C and Hamilton psychiatric Rating scale for Depression (HAM-D) scores (rs = 0.58, p < 0.001) Overall, our data demonstrated the validity of the Italian version of the AES-C for the assessment of apathy both in MCI and in AD patients.

Download Full-text

Occurrence of neuropsychiatric symptoms and psychiatric disorders in mild Alzheimer's disease and mild cognitive impairment subtypes

International Psychogeriatrics ◽

10.1017/s1041610210000281 ◽

2010 ◽

Vol 22 (4) ◽

pp. 629-640 ◽

Cited By ~ 66

Author(s):

Fulvia Di Iulio ◽

Katie Palmer ◽

Carlo Blundo ◽

Anna Rosa Casini ◽

Walter Gianni ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Psychiatric Disorders ◽

Neuropsychiatric Symptoms ◽

Neuropsychiatric Disorders ◽

Structured Interviews ◽

Night Time ◽

Amnestic Mci

ABSTRACTBackground: Neuropsychiatric disorders are common in cognitively impaired older persons, and associated with institutionalization and caregiver stress in Alzheimer's disease (AD). Few studies have compared the occurrence of both psychiatric disorders and neuropsychiatric symptoms in patients with AD and mild cognitive impairment (MCI) subtypes. We aimed to investigate the frequency of psychiatric disorders and neuropsychiatric symptoms in AD and MCI patients, compared to controls.Methods: We included 245 outpatients of a memory clinic in Rome, Italy (119 AD; 68 multidomain-MCI; 58 amnestic-MCI) and 107 controls. Categorical disorders of depression and apathy were diagnosed with structured interviews. Symptoms were evaluated with the Neuropsychiatric Inventory (NPI). The odds ratios (OR) of patients having neuropsychiatric symptoms compared to controls were calculated with logistic regression, adjusted for sociodemographic and clinical variables.Results: A large proportion of AD (49.6%) and multidomain-MCI (44.1%) patients had depression disorder. Apathy disorder was common in AD (51.3%) but less frequent in amnestic-MCI (6.9%) and multidomain-MCI (14.7%). AD patients were three times more likely to have depression disorders (OR = 3.0, CI = 1.1–7.6) or apathy (OR = 16.9, CI = 4.6–61.8) compared to amnestic-MCI, and seven times more likely to have apathy disorder than multidomain-MCI (OR = 7.5, CI = 3.0–19.2). After apathy and depression, the most prevalent neuropsychiatric symptoms in AD and MCI were anxiety, agitation, irritability, night-time behaviors, and appetite disturbances. There was an increasing prevalence of many neuropsychiatric symptoms with increasing severity of cognitive syndromes.Conclusions: Clinicians should consider the relevance of neuropsychiatric disorders and symptoms in patients with cognitive disturbances, and incorporate a thorough psychiatric examination in the evaluation of patients.

Download Full-text

Precuneus and Cingulate Cortex Atrophy and Hypometabolism in Patients with Alzheimer’s Disease and Mild Cognitive Impairment: MRI and18F-FDG PET Quantitative Analysis Using FreeSurfer

BioMed Research International ◽

10.1155/2015/583931 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 39

Author(s):

Matthieu Bailly ◽

Christophe Destrieux ◽

Caroline Hommet ◽

Karl Mondon ◽

Jean-Philippe Cottier ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cingulate Cortex ◽

Posterior Cingulate Cortex ◽

Regions Of Interest ◽

Posterior Cingulate ◽

Amnestic Mci ◽

Prodromal Ad

Objective.The objective of this study was to compare glucose metabolism and atrophy, in the precuneus and cingulate cortex, in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), using FreeSurfer.Methods.47 individuals (17 patients with AD, 17 patients with amnestic MCI, and 13 healthy controls (HC)) were included. MRI and PET images using18F-FDG (mean injected dose of 185 MBq) were acquired and analyzed using FreeSurfer to define regions of interest in the hippocampus, amygdala, precuneus, and anterior and posterior cingulate cortex. Regional volumes were generated. PET images were registered to the T1-weighted MRI images and regional uptake normalized by cerebellum uptake (SUVr) was measured.Results.Mean posterior cingulate volume was reduced in MCI and AD. SUVr were different between the three groups: mean precuneus SUVr was 1.02 for AD, 1.09 for MCI, and 1.26 for controls (p<0.05); mean posterior cingulate SUVr was 0.96, 1.06, and 1.22 for AD, MCI, and controls, respectively (p<0.05).Conclusion.We found graduated hypometabolism in the posterior cingulate cortex and the precuneus in prodromal AD (MCI) and AD, whereas atrophy was not significant. This suggests that the use of18F-FDG in these two regions could be a neurodegenerative biomarker.

Download Full-text

Integrative Base Ontology for the Research Analysis of Alzheimer’s Disease-Related Mild Cognitive Impairment

Frontiers in Neuroinformatics ◽

10.3389/fninf.2021.561691 ◽

2021 ◽

Vol 15 ◽

Author(s):

Alba Gomez-Valades ◽

Rafael Martinez-Tomas ◽

Mariano Rincon

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Functions ◽

Brain Areas ◽

The Stability ◽

Access To Data ◽

Building Life Cycle ◽

Transitional Phase

Early detection of mild cognitive impairment (MCI) has become a priority in Alzheimer’s disease (AD) research, as it is a transitional phase between normal aging and dementia. However, information on MCI and AD is scattered across different formats and standards generated by different technologies, making it difficult to work with them manually. Ontologies have emerged as a solution to this problem due to their capacity for homogenization and consensus in the representation and reuse of data. In this context, an ontology that integrates the four main domains of neurodegenerative diseases, diagnostic tests, cognitive functions, and brain areas will be of great use in research. Here, we introduce the first approach to this ontology, the Neurocognitive Integrated Ontology (NIO), which integrates the knowledge regarding neuropsychological tests (NT), AD, cognitive functions, and brain areas. This ontology enables interoperability and facilitates access to data by integrating dispersed knowledge across different disciplines, rendering it useful for other research groups. To ensure the stability and reusability of NIO, the ontology was developed following the ontology-building life cycle, integrating and expanding terms from four different reference ontologies. The usefulness of this ontology was validated through use-case scenarios.

Download Full-text