High rate of conversion to Alzheimer's disease in a cohort of amnestic MCI patients

2008 ◽  
Vol 20 (1) ◽  
pp. 96-108 ◽  
Author(s):  
Klaus Schmidtke ◽  
Sonja Hermeneit
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Performance ◽  
Word List ◽  
High Rate ◽  
Amnestic Mci ◽  
Prodromal Ad ◽  
List Learning ◽  
Study Population ◽  
Competing Causes

AbstractBackground: A large proportion of patients with amnestic mild cognitive impairment (MCI) progress to Alzheimer's disease (AD), but the rate of conversion is highly variable, depending on selection and inclusion criteria. In the present prospective study, amnestic MCI criteria were applied in order to enrich the study population with prodromal AD patients.Methods: A composite CERAD word list learning z-score of −1 was applied as a cut-off for memory performance at baseline. Competing causes of memory impairment other than prodromal AD were actively excluded. A cohort of 88 amnestic MCI patients was included; 75 were available for follow-up.Results: After a mean delay of 19 months, 44% were found to have converted to AD, corresponding to an annualized conversion rate of 28%. The rate of new diagnoses other than stable MCI or AD was 6%. Baseline neuropsychological variables were not instrumental to predict progression.Conclusion: Amnestic MCI patients, as identified by the present set of criteria, carry a high risk of median-term progression to AD.

Impact of Comorbid Depression on Serial Position Effects in Alzheimer’s Disease

GeroPsych ◽  
2014 ◽  
Vol 27 (4) ◽  
pp. 161-169 ◽  
Author(s):  
Nienke A. Hofrichter ◽  
Sandra Dick ◽  
Thomas G. Riemer ◽  
Carsten Schleussner ◽  
Monique Goerke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serial Position ◽  
Episodic Memory ◽  
Memory Performance ◽  
Memory Function ◽  
Word List ◽  
Position Effects ◽  
Serial Position Effects ◽  
List Memory

Hippocampal dysfunction and deficits in episodic memory have been reported for both Alzheimer’s disease (AD) and major depressive disorder (MDD). Primacy performance has been associated with hippocampus-dependent episodic memory, while recency may reflect working memory performance. In this study, serial position profiles were examined in a total of 73 patients with MDD, AD, both AD and MDD, and healthy controls (HC) by means of CERAD-NP word list memory. Primacy performance was most impaired in AD with comorbid MDD, followed by AD, MDD, and HC. Recency performance, on the other hand, was comparable across groups. These findings indicate that primacy in AD is impaired in the presence of comorbid MDD, suggesting additive performance decrements in this specific episodic memory function.

Executive dysfunction can explain word-list learning disability in very mild Alzheimer's disease: The Tajiri Project

2004 ◽  
Vol 58 (1) ◽  
pp. 54-60 ◽  
Author(s):  
RYUSAKU HASHIMOTO ◽  
KENICHI MEGURO ◽  
SATOSHI YAMAGUCHI ◽  
JUNICHI ISHIZAKI ◽  
HIROSHI ISHII ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning Disability ◽  
Word List ◽  
Executive Dysfunction ◽  
List Learning

scholarly journals 0421 Decreased Actigraphic Daytime Activity is Associated with Lower Memory Performance in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer’s Disease

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A161-A161
Author(s):  
E Pardilla-Delgado ◽  
L Ramirez Gomez ◽  
A Y Baena ◽  
M I Montes ◽  
Y Bocanegra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Performance ◽  
Word List ◽  
Brain Regions ◽  
Future Research ◽  
Daytime Activity ◽  
Mutation Carriers ◽  
Wrist Actigraphy ◽  
Circadian Dysfunction

Abstract Introduction Alzheimer’s disease (AD) impacts brain regions that control circadian regulation systems such as wakefulness and daytime physical activity. Recent evidence shows that AD pathology is damaging for wake-promoting neurons. Whether early changes in wakefulness and daytime activity occur during asymptomatic stages of familial AD (fAD) remains unknown. In this study, we aimed to investigate whether daytime activity differs between cognitively-unimpaired carriers of early-onset fAD and age-matched non-carrier family members. Further, we examined the associations between daytime activity and memory performance. Methods A total of 25 members of the large Colombian kindred with the Presenilin1 (PSEN1) E280A mutation were included in the study (9 mutation carriers and 16 non-carriers, mean age=38.2). PSEN1 mutation carriers develop dementia before the age of 50. All subjects underwent wrist actigraphy for 7-14 days to measure daytime activity (average activity per minute and per epoch), and completed the CERAD Word List Learning and the Free and Cued Selective Reminding Test (FCSRT). Results Compared to non-carriers, mutation carriers had less average daytime activity (Mann-Whitney U Test p=.04). Higher average daytime activity was associated with better memory recall in both the CERAD word list delayed recall (r=.47, p=.05) and the FCRST delayed total recall (r=.53, p=.02). No associations with age were observed. Conclusion Our results suggest that cognitively-unimpaired mutation carriers have reduced daytime activity, years before the onset of dementia. Reduced daytime activity in carriers is also associated with lower memory performance. Our preliminary findings add to the growing evidence that circadian dysfunction is present in early AD, and may play an important role in subsequent memory impairment. Future research with large samples is needed to further examine sleep and circadian dysfunction in asymptomatic individuals at genetic risk for AD. Support NIA 5R01AG054671-03 to YTQ

scholarly journals Low Cerebrospinal Fluid Amyloid-Beta Concentration Is Associated with Poorer Delayed Memory Recall in Women

2016 ◽  
Vol 6 (2) ◽  
pp. 303-312 ◽  
Author(s):  
Fanni Haapalinna ◽  
Teemu Paajanen ◽  
Janne Penttinen ◽  
Hannu Kokki ◽  
Merja Kokki ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Beta ◽  
Memory Performance ◽  
Word List ◽  
Cognitive Status ◽  
Csf Biomarkers ◽  
Memory Disorder ◽  
Biomarker Analysis

Background: Data on the association of memory performance with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are inconsistent. The Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-NB) is a commonly used validated cognitive tool; however, only few studies have examined its relationship with CSF biomarkers for AD. We studied the correlation of pathological changes in CSF biomarkers with various CERAD-NB subtests and total scores. Methods: Out of 79 subjects (36 men, mean age 70.5 years), 63 had undergone an assessment of cognitive status with CERAD-NB and a CSF biomarker analysis due to a suspected memory disorder, and 16 were controls with no memory complaint.Results: In women we found a significant correlation between CSF amyloid-beta (Aβ1-42) and several subtests measuring delayed recall. Word List Recall correlated with all markers: Aβ1-42 (r = 0.323, p = 0.035), tau (r = -0.304, p = 0.050) and hyperphosphorylated tau (r = -0.331, p = 0.046). No such correlations were found in men. Conclusions: CSF biomarkers correlate with delayed memory scores in CERAD-NB in women, and women may have more actual AD pathology at the time of the investigations than men.

scholarly journals 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

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
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.

scholarly journals Awareness of Cognitive Decline in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 13 ◽  
Author(s):  
Federica Cacciamani ◽  
Marion Houot ◽  
Geoffroy Gagliardi ◽  
Bruno Dubois ◽  
Sietske Sikkes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Meta Analysis ◽  
Self Report ◽  
Original Research ◽  
Cognitive Changes ◽  
Amnestic Mci ◽  
Preclinical Ad ◽  
Prodromal Ad

Background: Identifying a poor degree of awareness of cognitive decline (ACD) could represent an early indicator of Alzheimer's disease (AD).Objectives: (1) to understand whether there is evidence of poor ACD in the pre-dementia stages of AD; (2) to summarize the main findings obtained investigating ACD in AD; (3) to propose a conceptual framework.Data Sources: We searched Scopus, Pubmed, and the reference lists for studies published up to August 2020. Original research articles must report a measure of ACD and included individuals with AD dementia, or prodromal AD (or MCI), or being at risk for AD.Data Synthesis: All studies covering preclinical, prodromal, and AD dementia were systematically reviewed. We intended to perform a meta-analysis of empirical studies on preclinical AD or prodromal AD (or MCI), to compare ACD between clinical groups. Due to the paucity of literature on preclinical AD, meta-analysis was only possible for prodromal AD (or MCI) studies.Results: We systematically reviewed 283 articles, and conducted a meta-analysis of 18 articles on prodromal AD (or MCI), showing that ACD was not significantly different between patients with amnestic and non-amnestic MCI (SMD = 0.09, p = 0.574); ACD was significantly poorer in amnestic MCI (SMD = −0.56, p = 0.001) and mild AD (SMD = −1.39, p &lt; 0.001) than in controls; ACD was also significantly poorer in mild AD than in amnestic MCI (SMD = −0.75, p &lt; 0.001), as well as poorer than in non-amnestic MCI (SMD = −1.00, p &lt; 0.001). We also discuss key findings on ACD in AD, such as its neural and cognitive correlates.Conclusions and Implications: We propose that patients may be complaining of their initial subtle cognitive changes, but ACD would soon start to decrease. The individual would show mild anosognosia in the MCI stage, and severe anosognosia in dementia. The evaluation of ACD (comparing self-report to cognitive scores or to informant-report) could be useful to guide the clinician toward a timely diagnosis, and in trials targeting early-stage AD.

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

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.

scholarly journals Plasma contact factors as novel biomarkers for diagnosing Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jung Eun Park ◽  
Do Sung Lim ◽  
Yeong Hee Cho ◽  
Kyu Yeong Choi ◽  
Jang Jae Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Stage ◽  
Area Under The Curve ◽  
Contact System ◽  
Plasma Diagnostic ◽  
Vascular Abnormalities ◽  
Prodromal Ad ◽  
Novel Biomarkers

Abstract Background Alzheimer’s disease (AD) is the most common cause of dementia and most of AD patients suffer from vascular abnormalities and neuroinflammation. There is an urgent need to develop novel blood biomarkers capable of diagnosing Alzheimer’s disease (AD) at very early stage. This study was performed to find out new accurate plasma diagnostic biomarkers for AD by investigating a direct relationship between plasma contact system and AD. Methods A total 101 of human CSF and plasma samples from normal and AD patients were analyzed. The contact factor activities in plasma were measured with the corresponding specific peptide substrates. Results The activities of contact factors (FXIIa, FXIa, plasma kallikrein) and FXa clearly increased and statistically correlated as AD progresses. We present here, for the first time, the FXIIa cut-off scores to as: > 26.3 U/ml for prodromal AD [area under the curve (AUC) = 0.783, p < 0.001] and > 27.2 U/ml for AD dementia (AUC = 0.906, p < 0.001). We also describe the cut-off scores from the ratios of CSF Aβ1–42 versus the contact factors. Of these, the representative ratio cut-off scores of Aβ1–42/FXIIa were to be: < 33.8 for prodromal AD (AUC = 0.965, p < 0.001) and < 27.44 for AD dementia (AUC = 1.0, p < 0.001). Conclusion The activation of plasma contact system is closely associated with clinical stage of AD, and FXIIa activity as well as the cut-off scores of CSF Aβ1–42/FXIIa can be used as novel accurate diagnostic AD biomarkers.

scholarly journals Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina F. de Veij Mestdagh ◽  
Jaap A. Timmerman ◽  
Frank Koopmans ◽  
Iryna Paliukhovich ◽  
Suzanne S. M. Miedema ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Memory Performance ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation

AbstractHibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arousal sequence in mice does not induce dendrite retraction and synapse loss as observed in seasonal hibernators. Instead, it increases hippocampal long-term potentiation and contextual fear memory. This is accompanied by increased levels of key postsynaptic proteins and mitochondrial complex I and IV proteins, indicating mitochondrial reactivation and enhanced synaptic plasticity upon arousal. Interestingly, a single torpor and arousal sequence was also sufficient to restore contextual fear memory in an APP/PS1 mouse model of Alzheimer’s disease. Our study demonstrates that torpor in mice evokes an exceptional state of hippocampal plasticity and that naturally occurring plasticity mechanisms during torpor provide an opportunity to identify unique druggable targets for the treatment of cognitive impairment.

Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer’s Disease

2021 ◽  
pp. 1-9
Author(s):  
Jairo E. Martinez ◽  
Enmanuelle Pardilla-Delgado ◽  
Edmarie Guzmán-Vélez ◽  
Clara Vila-Castelar ◽  
Rebecca Amariglio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Decline ◽  
Verbal Memory ◽  
Autosomal Dominant ◽  
Memory Performance ◽  
Subjective Cognitive Decline ◽  
Mutation Carriers ◽  
Study Partner

Abstract Objective: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance. Methods: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. Results: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. Conclusions: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

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