scholarly journals Are Empirically-Derived Subtypes of Mild Cognitive Impairment Consistent with Conventional Subtypes?

2013 ◽  
Vol 19 (6) ◽  
pp. 635-645 ◽  
Author(s):  
Lindsay R. Clark ◽  
Lisa Delano-Wood ◽  
David J. Libon ◽  
Carrie R. McDonald ◽  
Daniel A. Nation ◽  
...  

AbstractGiven the importance of identifying dementia prodromes for future treatment efforts, we examined two methods of diagnosing mild cognitive impairment (MCI) and determined whether empirically-derived MCI subtypes of these diagnostic methods were consistent with one another as well as with conventional MCI subtypes (i.e., amnestic, non-amnestic, single-domain, multi-domain). Participants were diagnosed with MCI using either conventional Petersen/Winblad criteria (n = 134; >1.5 SDs below normal on one test within a cognitive domain) or comprehensive neuropsychological criteria developed by Jak et al. (2009) (n = 80; >1 SD below normal on two tests within a domain), and the resulting samples were examined via hierarchical cluster and discriminant function analyses. Results showed that neuropsychological profiles varied depending on the criteria used to define MCI. Both criteria revealed an Amnestic subtype, consistent with prodromal Alzheimer's disease (AD), and a Mixed subtype that may capture individuals in advanced stages of MCI. The comprehensive criteria uniquely yielded Dysexecutive and Visuospatial subtypes, whereas the conventional criteria produced a subtype that performed within normal limits, suggesting its susceptibility to false positive diagnostic errors. Whether these empirically-derived MCI subtypes correspond to dissociable neuropathologic substrates and represent reliable prodromes of dementia will require additional follow-up. (JINS, 2013, 19, 1–11)

2020 ◽  
Vol 78 (1) ◽  
pp. 371-386
Author(s):  
Lisa V. Graves ◽  
Emily C. Edmonds ◽  
Kelsey R. Thomas ◽  
Alexandra J. Weigand ◽  
Shanna Cooper ◽  
...  

Background: Research suggests that actuarial neuropsychological criteria improve the accuracy of mild cognitive impairment (MCI) diagnoses relative to conventional diagnostic methods. Objective: We sought to examine the utility of actuarial criteria relative to consensus diagnostic methods used in the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS), and more broadly across the continuum of normal aging, MCI, and dementia. Methods: We compared rates of cognitively normal (CN), MCI, and dementia diagnoses at baseline using actuarial versus consensus diagnostic methods in 1524 individuals from the NACC UDS. Results: Approximately one-third (33.59%) of individuals diagnosed as CN and more than one-fifth (22.03%) diagnosed with dementia based on consensus methods, met actuarial criteria for MCI. Many participants diagnosed with MCI via consensus methods also appeared to represent possible diagnostic errors. Notably, the CNa/CNc group (i.e., participants diagnosed as CN based on both actuarial [a] and consensus [c] criteria) had a lower proportion of apolipoprotein E ɛ4 carriers than the MCIa/MCIc group, which in turn had a lower proportion of ɛ4 carriers than the dementia (Dem)a/Demc group. Proportions of ɛ4 carriers were comparable between the CNa/CNc and CNa/MCIc, MCIa/MCIc and MCIa/CNc, MCIa/MCIc and MCIa/Demc, and Dema/Demc and Dema/MCIc groups. These results were largely consistent with diagnostic agreement/discrepancy group comparisons on neuropsychological performance. Conclusion: The present results extend previous findings and suggest that actuarial neuropsychological criteria may enhance diagnostic accuracy relative to consensus methods, and across the wider continuum of normal aging, MCI, and dementia. Findings have implications for both clinical practice and research.


Author(s):  
Tahreem Ghazal Siddiqui ◽  
Timothy Whitfield ◽  
Sudhakar Janaki Praharaju ◽  
Dilman Sadiq ◽  
Hiba Kazmi ◽  
...  

<b><i>Introduction:</i></b> Fifteen percent of people with mild cognitive impairment (MCI) will progress to dementia within 2 years. There is increasing focus on the evaluation of biomarkers which point towards the underlying pathology. This enables better prediction of clinical outcomes. Early diagnosis of the dementia subtype is crucial for appropriate management and accurate prognosis. The aim of this study was to compare MRI measures in stable mild cognitive impairment patients (stable-MCI), prodromal Alzheimer’s disease (pro-AD), and prodromal dementia with Lewy bodies (pro-DLB). <b><i>Methods:</i></b> Out of 1,814 patients assessed in Essex memory clinic between 2002 and 2017, 424 had MCI at baseline with follow-up data. All patients underwent comprehensive clinical and cognitive assessment at each assessment. MRI scans were acquired at patients’ baseline assessment, corresponding to the time of initial MCI clinical diagnosis. Patients were grouped according to their diagnosis at the end of follow-up. All baseline scans were visually rated according to established rating scales for medial temporal atrophy (MTA), global cortical atrophy (GCA), and white matter lesions (WMLs). <b><i>Results:</i></b> MRI scans were available for 28 pro-DLB patients and were matched against 27 pro-AD and 28 stable-MCI patients for age, sex, and education. The mean follow-up duration was 34 months for the pro-AD group, 27 months for the pro-DLB group, and 21 months for the stable-MCI group. MTA scores were significantly greater in pro-AD patients compared to pro-DLB (<i>p</i> = 0.047) and stable-MCI patients (<i>p</i> = 0.012). There was no difference on GCA or WMLs between pro-AD, pro-DLB, and stable-MCI. <b><i>Conclusions:</i></b> This study indicates that a simple visual rating of MTA at the stage of MCI already differs at a group level between patients that progress to AD, DLB, or continue to be stable-MCI. This could aid clinicians to differentiate between MCI patients who are likely to develop AD, versus those who might progress to DLB or remain stable.


2018 ◽  
Vol 30 (9) ◽  
pp. 1417-1417
Author(s):  
Richard Camicioli ◽  
Kirstie Mcdermott

We thank Ms. Horne et al. for the clarification of our misquoting of their paper (Wood et al., 2016). They clarify that 21% of their overall sample of patients with Parkinson's disease (PD-MCI) converted to dementia in over four years, which we erroneously attributed to the mild cognitive impairment (MCI) group in our discussion (McDermott et al., 2017). This was virtually identical to our overall conversion rate of 20%. Their conversion rate of patients with PD-MCI, as defined by two cognitive tests impaired (1.5 SD) within a single cognitive domain, was 51%, whereas the conversion rate was 38% when the PD-MCI group included patients with impairment within and between cognitive domains. Their conversion rates are similar to our rate of 42% (as defined with 1.5 SD impairment within or across domains) and the rate of 39% in a study with five-years of follow-up of incident cases (Pedersen et al., 2017). Our overall conversion occurred over a slightly shorter time span. In addition to conversion rates, all the studies acknowledge that some patients can revert to normal cognitive status, which varies based on classification criteria and length of follow-up. Comparable conversion across studies using similar criteria is reassuring and can encourage planning of targeted interventions (Hoogland et al., 2017).


2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  

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.


2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Jiangyi Xia ◽  
Ali Mazaheri ◽  
Katrien Segaert ◽  
David P Salmon ◽  
Danielle Harvey ◽  
...  

Abstract Reliable biomarkers of memory decline are critical for the early detection of Alzheimer’s disease. Previous work has found three EEG measures, namely the event-related brain potential P600, suppression of oscillatory activity in the alpha frequency range (∼10 Hz) and cross-frequency coupling between low theta/high delta and alpha/beta activity, each of which correlates strongly with verbal learning and memory abilities in healthy elderly and patients with mild cognitive impairment or prodromal Alzheimer’s disease. In the present study, we address the question of whether event-related or oscillatory measures, or a combination thereof, best predict the decline of verbal memory in mild cognitive impairment and Alzheimer’s disease. Single-trial correlation analyses show that despite a similarity in their time courses and sensitivities to word repetition, the P600 and the alpha suppression components are minimally correlated with each other on a trial-by-trial basis (generally |rs| &lt; 0.10). This suggests that they are unlikely to stem from the same neural mechanism. Furthermore, event-related brain potentials constructed from bandpass filtered (delta, theta, alpha, beta or gamma bands) single-trial data indicate that only delta band activity (1–4 Hz) is strongly correlated (r = 0.94, P &lt; 0.001) with the canonical P600 repetition effect; event-related potentials in higher frequency bands are not. Importantly, stepwise multiple regression analyses reveal that the three event-related brain potential/oscillatory measures are complementary in predicting California Verbal Learning Test scores (overall R2’s in 0.45–0.63 range). The present study highlights the importance of combining EEG event-related potential and oscillatory measures to better characterize the multiple mechanisms of memory failure in individuals with mild cognitive impairment or prodromal Alzheimer’s disease.


2021 ◽  
pp. 026988112110085
Author(s):  
JZ Petersen ◽  
J Macoveanu ◽  
HL Kjærstad ◽  
GM Knudsen ◽  
LV Kessing ◽  
...  

Background: Mood disorders are often associated with persistent cognitive impairments. However, pro-cognitive treatments are essentially lacking. This is partially because of poor insight into the neurocircuitry abnormalities underlying these deficits and their change with illness progression. Aims: This functional magnetic resonance imaging (fMRI) study investigates the neuronal underpinnings of cognitive impairments and neuronal change after mood episodes in remitted patients with bipolar disorder (BD) using a hippocampus-based picture encoding paradigm. Methods: Remitted patients with BD ( n=153) and healthy controls ( n=52) were assessed with neuropsychological tests and underwent fMRI while performing a strategic picture encoding task. A subgroup of patients ( n=43) were rescanned after 16 months. We conducted data-driven hierarchical cluster analysis of patients’ neuropsychological data and compared encoding-related neuronal activity between the resulting neurocognitive subgroups. For patients with follow-up data, effects of mood episodes were assessed by comparing encoding-related neuronal activity change in BD patients with and without episode(s). Results: Two neurocognitive subgroups were revealed: 91 patients displayed cognitive impairments while 62 patients were cognitively normal. No neuronal activity differences were observed between neurocognitive subgroups within the dorsal cognitive control network or hippocampus. However, exploratory whole-brain analysis revealed lower activity within a small region of middle temporal gyrus in impaired patients, which significantly correlated with poorer neuropsychological performance. No changes were observed in encoding-related neuronal activity or picture recall accuracy with the occurrence of mood episode(s) during the follow-up period. Conclusion: Memory encoding fMRI paradigms may not capture the neuronal underpinnings of cognitive impairment or effects of mood episodes.


Author(s):  
Iván Galtier ◽  
Antonieta Nieto ◽  
María Mata ◽  
Jesús N. Lorenzo ◽  
José Barroso

ABSTRACT Objective: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in Parkinson’s disease (PD) are considered as the risk factors for dementia (PDD). Posterior cortically based functions, such as visuospatial and visuoperceptual (VS-VP) processing, have been described as predictors of PDD. However, no investigations have focused on the qualitative analysis of the Judgment of Line Orientation Test (JLOT) and the Facial Recognition Test (FRT) in PD-SCD and PD-MCI. The aim of this work was to study the VS-VP errors in JLOT and FRT. Moreover, these variables are considered as predictors of PDD. Method: Forty-two PD patients and 19 controls were evaluated with a neuropsychological protocol. Patients were classified as PD-SCD and PD-MCI. Analyses of errors were conducted following the procedure described by Ska, Poissant, and Joanette (1990). Follow-up assessment was conducted to a mean of 7.5 years after the baseline. Results: PD-MCI patients showed a poor performance in JLOT and FRT total score and made a greater proportion of severe intraquadrant (QO2) and interquadrant errors (IQO). PD-SCD showed a poor performance in FRT and made mild errors in JLOT. PD-MCI and QO2/IQO errors were independent risk factors for PDD during the follow-up. Moreover, the combination of both PD-MCI diagnosis and QO2/IQO errors was associated with a greater risk. Conclusions: PD-MCI patients presented a greater alteration in VS-VP processing observable by the presence of severe misjudgments. PD-SCD patients also showed mild difficulties in VS-SP functions. Finally, QO2/IQO errors in PD-MCI are a useful predictor of PDD, more than PD-MCI diagnosis alone.


2020 ◽  
Vol 32 (S1) ◽  
pp. 91-91

AUTHORS:Kerstin Johansson, Karolina Thömkvist, Ingmar Skoog and Sacuiu SF* (*presenter)OBJECTIVE:To determine the effects of electroconvulsive therapy (ECT) in major depression in relation to the development of dementia during long-term follow-up.METHOD:In an observational clinical prospective study of consecutive patients 70 years and older diagnosed with major depression at baseline 2000-2004 (n=1090), who were free of dementia and received antidepressant treatment, with or without ECT, we sought to determine if cognitive decline (mild cognitive impairment and dementia) during 15 -year follow-up was associated with receiving ECT at baseline. The control group was selected among the participants in the Gothenburg H70 Birth Cohort Studies matched by age group and sex 1:1.RESULTS:Among patients with affective syndromes 7% received ECT. During follow-up, 157 patients were diagnosed with dementia, equal proportions among those who received ECT (14.5%) and those who did not receive ECT (14.5%). The relation between ECT and cognitive decline remained non-significant irrespective antidepressive medication or presence of mild cognitive impairment at baseline.CONCLUSION:Preliminary results indicate that ECT was not associated with the development of cognitive decline in the long-term in a hospital-based cohort of 70+ year-olds. The results remain to verify against controls from a representative community sample.


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