Minor neuropsychological deficits in patients with subjective cognitive decline

ObjectiveTo determine the nature and extent of minor neuropsychological deficits in patients with subjective cognitive decline (SCD) and their association with CSF biomarkers of Alzheimer disease (AD).MethodWe analyzed data from n = 449 cognitively normal participants (n = 209 healthy controls, n = 240 patients with SCD) from an interim data release of the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE). An extensive neuropsychological test battery was applied at baseline for which we established a latent, 5 cognitive domain factor structure comprising learning and memory, executive functions, language abilities, working memory, and visuospatial functions. We compared groups in terms of global and domain-specific performance and correlated performance with different CSF markers of AD pathology.ResultsWe observed worse performance (Cohen d = ≈0.25–0.5, adjusted for age, sex differences with analysis of covariance) in global performance, memory, executive functions, and language abilities for the SCD group compared to healthy controls. In addition, worse performance in these domains was moderately (r = ≈0.3) associated with lower CSF β-amyloid42/40 and CSF β-amyloid42/phosphorylated tau181 in the whole sample and specifically in the SCD subgroup.ConclusionsWithin the spectrum of clinically unimpaired (i.e., before mild cognitive impairment) cognitive performance, SCD is associated with minor deficits in memory, executive function, and language abilities. The association of these subtle cognitive deficits with AD CSF biomarkers speaks to their validity and potential use for the early detection of underlying preclinical AD.

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Assessing visuo-constructive functions in patients with subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease with the Vienna Visuo-Constructional Test 3.0 (VVT 3.0)

Neuropsychiatrie ◽

10.1007/s40211-021-00385-x ◽

2021 ◽

Author(s):

Noel Valencia ◽

Johann Lehrner

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Multinomial Logistic Regression ◽

Subjective Cognitive Decline ◽

Healthy Controls ◽

Considerable Potential ◽

Multinomial Logistic Regression Analysis

Summary Background Visuo-Constructive functions have considerable potential for the early diagnosis and monitoring of disease progression in Alzheimer’s disease. Objectives Using the Vienna Visuo-Constructional Test 3.0 (VVT 3.0), we measured visuo-constructive functions in subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and healthy controls to determine whether VVT performance can be used to distinguish these groups. Materials and methods Data of 671 participants was analyzed comparing scores across diagnostic groups and exploring associations with relevant clinical variables. Predictive validity was assessed using Receiver Operator Characteristic curves and multinomial logistic regression analysis. Results We found significant differences between AD and the other groups. Identification of cases suffering from visuo-constructive impairment was possible using VVT scores, but these did not permit classification into diagnostic subgroups. Conclusions In summary, VVT scores are useful indicators for visuo-constructive impairment but face challenges when attempting to discriminate between several diagnostic groups.

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Protocols for cognitive enhancement. A user manual for Brain Health Services—part 5 of 6

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00844-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Andrea Brioschi Guevara ◽

Melanie Bieler ◽

Daniele Altomare ◽

Marcelo Berthier ◽

Chantal Csajka ◽

...

Keyword(s):

Systematic Review ◽

Cognitive Impairment ◽

Executive Functions ◽

Cognitive Decline ◽

Physical Training ◽

Cognitive Enhancement ◽

Memory Performance ◽

Subjective Cognitive Decline ◽

Strategic Learning

AbstractCognitive complaints in the absence of objective cognitive impairment, observed in patients with subjective cognitive decline (SCD), are common in old age. The first step to postpone cognitive decline is to use techniques known to improve cognition, i.e., cognitive enhancement techniques.We aimed to provide clinical recommendations to improve cognitive performance in cognitively unimpaired individuals, by using cognitive, mental, or physical training (CMPT), non-invasive brain stimulations (NIBS), drugs, or nutrients. We made a systematic review of CMPT studies based on the GRADE method rating the strength of evidence.CMPT have clinically relevant effects on cognitive and non-cognitive outcomes. The quality of evidence supporting the improvement of outcomes following a CMPT was high for metamemory; moderate for executive functions, attention, global cognition, and generalization in daily life; and low for objective memory, subjective memory, motivation, mood, and quality of life, as well as a transfer to other cognitive functions. Regarding specific interventions, CMPT based on repeated practice (e.g., video games or mindfulness, but not physical training) improved attention and executive functions significantly, while CMPT based on strategic learning significantly improved objective memory.We found encouraging evidence supporting the potential effect of NIBS in improving memory performance, and reducing the perception of self-perceived memory decline in SCD. Yet, the high heterogeneity of stimulation protocols in the different studies prevent the issuing of clear-cut recommendations for implementation in a clinical setting. No conclusive argument was found to recommend any of the main pharmacological cognitive enhancement drugs (“smart drugs”, acetylcholinesterase inhibitors, memantine, antidepressant) or herbal extracts (Panax ginseng, Gingko biloba, and Bacopa monnieri) in people without cognitive impairment.Altogether, this systematic review provides evidence for CMPT to improve cognition, encouraging results for NIBS although more studies are needed, while it does not support the use of drugs or nutrients.

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Reduced Lexical Access to Verbs in Individuals With Subjective Cognitive Decline

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317518790541 ◽

2018 ◽

Vol 34 (1) ◽

pp. 5-15 ◽

Cited By ~ 6

Author(s):

Joël Macoir ◽

Anne Lafay ◽

Carol Hudon

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Lexical Access ◽

Assessment Tools ◽

Subjective Cognitive Decline ◽

Object Naming ◽

Potential Contribution ◽

Healthy Controls ◽

Action Naming

The detection of cognitive impairment in individuals with subjective cognitive decline (SCD) may improve detection of the emergence of Alzheimer’s disease (AD) pathology. This detection is challenging, however, given the lack of sensitive assessment tools. The main objective of this study was to determine the potential contribution of word production tasks to the detection of cognitive impairment in SCD. The performances of 20 individuals with SCD, healthy controls (HCs), and individuals with mild cognitive impairment (MCI) were compared on object and action naming and free fluency tasks. Participants with SCD performed similarly to HCs, while both groups differed significantly from participants with MCI in object naming and object fluency. Results showed that participants with SCD were at the midpoint between HCs and participants with MCI in action naming. They also revealed a HCs > SCD = MCI pattern in action fluency. This study provides evidence that verb production is impaired in SCD and that SCD is a pre-MCI condition.

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Neuropsychiatric symptoms in at-risk groups for AD dementia and their association with worry and AD biomarkers—results from the DELCODE study

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00701-7 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Lena Sannemann ◽

◽

Ann-Katrin Schild ◽

Slawek Altenstein ◽

Claudia Bartels ◽

...

Keyword(s):

At Risk ◽

Clinical Trials ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Neuropsychiatric Symptoms ◽

Geriatric Depression Scale ◽

Depression Scale ◽

Risk Groups ◽

Subjective Cognitive Decline ◽

Healthy Controls

Abstract Background Early identification of individuals at risk of dementia is mandatory to implement prevention strategies and design clinical trials that target early disease stages. Subjective cognitive decline (SCD) and neuropsychiatric symptoms (NPS) have been proposed as potential markers for early manifestation of Alzheimer’s disease (AD). We aimed to investigate the frequency of NPS in SCD, in other at-risk groups, in healthy controls (CO), and in AD patients, and to test the association of NPS with AD biomarkers, with a particular focus on cognitively unimpaired participants with or without SCD-related worries. Methods We analyzed data of n = 687 participants from the German DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study, including the diagnostic groups SCD (n = 242), mild cognitive impairment (MCI, n = 115), AD (n = 77), CO (n = 209), and first-degree relatives of AD patients (REL, n = 44). The Neuropsychiatric Inventory Questionnaire (NPI-Q), Geriatric Depression Scale (GDS-15), and Geriatric Anxiety Inventory (GAI-SF) were used to assess NPS. We examined differences of NPS frequency between diagnostic groups. Logistic regression analyses were carried out to further investigate the relationship between NPS and cerebrospinal fluid (CSF) AD biomarkers, focusing on a subsample of cognitively unimpaired participants (SCD, REL, and CO), who were further differentiated based on reported worries. Results The numbers of reported NPS, depression scores, and anxiety scores were significantly higher in subjects with SCD compared to CO. The quantity of reported NPS in subjects with SCD was lower compared to the MCI and AD group. In cognitively unimpaired subjects with worries, low Aß42 was associated with higher rates of reporting two or more NPS (OR 0.998, 95% CI 0.996–1.000, p < .05). Conclusion These findings give insight into the prevalence of NPS in different diagnostic groups, including SCD and healthy controls. NPS based on informant report seem to be associated with underlying AD pathology in cognitively unimpaired participants who worry about cognitive decline. Trial registration German Clinical Trials Register DRKS00007966. Registered 4 May 2015.

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Use of Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Risk in Mild Cognitive Impairment and Subjective Cognitive Decline in Routine Clinical Care in Germany

Journal of Alzheimer s Disease ◽

10.3233/jad-200794 ◽

2020 ◽

Vol 78 (3) ◽

pp. 1137-1148

Author(s):

Claudia Bartels ◽

Anna Kögel ◽

Mark Schweda ◽

Jens Wiltfang ◽

Michael Pentzek ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Clinical Care ◽

Subjective Cognitive Decline ◽

Csf Biomarkers ◽

Routine Clinical Care ◽

Biomarker Analysis ◽

Csf Biomarker

Background: The National Institute of Aging and Alzheimer’s Association’s diagnostic recommendations for preclinical Alzheimer’s disease (AD) and mild cognitive impairment (MCI) define AD by pathological processes which can be detected by biomarkers. These criteria were established as part of a research framework intended for research purposes but progressively enter the clinical practice. Objective: We investigated the availability, frequency of use, interpretation, and therapeutic implications of biomarkers for the etiologic diagnosis and prognosis in MCI and subjective cognitive decline (SCD) in routine clinical care. Methods: We conducted a cross-sectional questionnaire survey among 215 expert dementia centers (hospitals and memory clinics) in Germany. Results: From the 98 centers (45.6% of contacted centers) included, two-thirds reported use of the cerebrospinal fluid (CSF) biomarkers Aβ42, tau, and phospho-tau in the diagnostic workup of MCI and one third in SCD. CSF biomarker analysis was more often employed by neurological (MCI 84%; SCD 42%) compared to psychiatric institutions (MCI 61%; SCD 33%; p≤0.001). Although dementia experts disagreed on the risk of progression associated with different CSF biomarker constellations, CSF biomarker results guided therapeutic decisions: ∼40% of responders reported to initiate cholinesterase inhibitor therapy in MCI and 18% in SCD (p = 0.006), given that all CSF biomarkers were in the pathological range. Conclusion: Considering the vast heterogeneity among dementia expert centers in use of CSF biomarker analysis, interpretation of results, and therapeutic consequences, a standardization of biomarker-based diagnosis practice in pre-dementia stages is needed.

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Semantic memory and depressive symptoms in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease

International Psychogeriatrics ◽

10.1017/s1041610217000394 ◽

2017 ◽

Vol 29 (7) ◽

pp. 1123-1135 ◽

Cited By ~ 9

Author(s):

J. Lehrner ◽

G. Coutinho ◽

P. Mattos ◽

D. Moser ◽

M. Pflüger ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Depressive Symptoms ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Semantic Memory ◽

Semantic Knowledge ◽

Subjective Cognitive Decline ◽

Healthy Controls

ABSTRACTBackground:Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment.Methods:323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated.Results:Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS.Conclusions:We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.

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Facial emotion recognition in patients with subjective cognitive decline and mild cognitive impairment

International Psychogeriatrics ◽

10.1017/s1041610215001520 ◽

2015 ◽

Vol 28 (3) ◽

pp. 477-485 ◽

Cited By ~ 8

Author(s):

J. Pietschnig ◽

R. Aigner-Wöber ◽

N. Reischenböck ◽

I. Kryspin-Exner ◽

D. Moser ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Emotion Recognition ◽

Recognition Performance ◽

Test Battery ◽

Facial Emotion Recognition ◽

Facial Emotion ◽

Subjective Cognitive Decline ◽

Healthy Controls

ABSTRACTBackground:Deficits in facial emotion recognition (FER) have been shown to substantially impair several aspects in everyday life of affected individuals (e.g. social functioning). Presently, we aim at assessing differences in emotion recognition performance in three patient groups suffering from mild forms of cognitive impairment compared to healthy controls.Methods:Performance on a concise emotion recognition test battery (VERT-K) of 68 patients with subjective cognitive decline (SCD), 44 non-amnestic (non-aMCI), and 25 amnestic patients (aMCI) with mild cognitive impairment (MCI) was compared with an age-equivalent sample of 138 healthy controls all of which were recruited within the framework of the Vienna Conversion to Dementia Study. Additionally, patients and controls underwent individual assessment using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (NTBV), the Beck Depression Inventory (BDI), and a measure of premorbid IQ (WST).Results:Type of diagnosis showed a significant effect on emotion recognition performance, indicating progressively deteriorating results as severity of diagnosis increased. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohen's ds from −0.30 to −0.83) except for SCD versus controls. Moreover, emotion recognition performance was higher in women and positively associated with premorbid IQ.Conclusions:Our findings indicate substantial effects of progressive neurological damage on emotion recognition in patients. Importantly, emotion recognition deficits were observable in non-amnestic patients as well, thus conceivably suggesting associations between decreased recognition performance and global cognitive decline. Premorbid IQ appears to act as protective factor yielding lesser deficits in patients showing higher IQs.

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The FNAME yields equivalent results differentiating amnestic mild cognitive impairment from subjective cognitive decline and healthy controls in Mexico and the Netherlands

Alzheimer s & Dementia ◽

10.1002/alz.044333 ◽

2020 ◽

Vol 16 (S6) ◽

Author(s):

Juan Francisco Flores‐Vazquez ◽

Iris Van der Kolk ◽

José Juan Contreras‐López ◽

Cecilia Cruz‐Contreras ◽

Rutger A. Stegeman ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

The Netherlands ◽

Cognitive Decline ◽

Amnestic Mild Cognitive Impairment ◽

Subjective Cognitive Decline ◽

Healthy Controls

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The Neutrophil and Platelet to Lymphocyte Ratios in People with Subjective, Mild Cognitive Impairment and Early Alzheimer's Disease

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1099 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S655-S655

Author(s):

T. Kalelioglu ◽

M. Yuruyen ◽

G. Gultekin ◽

H. Yavuzer ◽

Y. Ozturk ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Systemic Inflammation ◽

Subjective Cognitive Decline ◽

Control Group ◽

Healthy Controls ◽

Lymphocyte Ratio

BackgroundIn this study we aimed to explore the role of inflammation in subjects with mild Alzheimer dementia (AD), mild cognitive impairment (MCI) and subjective cognitive decline (SCD) via new potential inflammation markers of Neutrophil-lymphocyte ratio (NLR) and Platelet-lymphocyte ratio (PLR). NLR and PLR are useful and cost-effective biomarkers, showing peripheral systemic inflammation, were previously shown in neuropsychiatric disorders [1].MethodsIn screening phase the patients were assessed with mini-mental state examination, clinical dementia rating scale (CDR), geriatric depression scale (GDS) and Hachinski Ischemic Scale (HIS) after unstructured psychiatric interview according to diagnostic and statistical manual of mental disorder, Text Revised (DSM-IV, TR). Spectrum of cognitive decline includes 31 patients with mild Alzheimer's disease, 30 subjects with mild cognitive impairment, 31 individuals with subjective cognitive decline. Thirty-one healthy controls enrolled to the study.ResultsNLR value of patients with AD was 2.38 ± 0.81, subjects with MCI was 2.48 ± 1.19, SCD group was 2.24 ± 1.11 and control group was 1.85 ± 0.80. NLR was significantly higher in AD and MCI groups when compared with control group (P = 0.006, P = 0.03, respectively). Platelet-lymphocyte ratio was not correlated with cognitive impairment. Neutrophil counts were indifferent when comparing either of groups. Lymphocyte levels were significantly lower in each of cognitive decline groups when compared to healthy controls.ConclusionThe present findings suggest that systemic inflammation may have a role in developing Alzheimer's Disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Basal forebrain atrophy along the Alzheimer’s disease spectrum and its relevance for subjective cognitive decline

10.21203/rs.3.rs-20438/v1 ◽

2020 ◽

Author(s):

Shumei Li ◽

Michel J. Grothe ◽

Marcel Daamen ◽

Steffen Wolfsgruber ◽

Frederic Brosseron ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Basal Forebrain ◽

Nucleus Basalis ◽

Nucleus Basalis Of Meynert ◽

Subjective Cognitive Decline ◽

Healthy Controls ◽

Cholinergic Basal Forebrain

Abstract Background There is growing evidence in the literature that the cholinergic basal forebrain might be one of the earliest affected structures in Alzheimer’s disease (AD). Recent data suggest that individuals with preclinical Alzheimer’s pathology already show atrophy of the posterior nucleus basalis of Meynert and that this even precedes the atrophy of the entorhinal cortex. Here we investigated whether basal forebrain volume reductions might not only be detectable in the mild cognitive impairment (MCI) and dementia stage of AD, but also in subjective cognitive decline (SCD) individuals who represent an at-risk population for preclinical AD, and examine the relationship with cognitive performance and amyloid-beta pathology. Methods Basal forebrain volumes of 341 participants from the multi-center German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study, including 135 healthy controls, 110 SCD, 60 MCI, and 36 AD, were analyzed using high-resolution T1-weighted images. Healthy controls and SCD participants were further grouped into amyloid-positive and amyloid-negative cases according to their cerebrospinal fluid Aβ42/40 ratio. Associations between basal forebrain volume, neuropsychological performance, and amyloid load were evaluated. Results Apart from confirming progressive basal forebrain atrophy from MCI to AD, atrophy of the posterior of nucleus basalis of Meynert was also observed in subjective cognitive decline with confirmed evidence for preclinical Alzheimer’s pathology, based on the Aβ42/40 ratio. This atrophy was neither evident in subjects with SCD without amyloid pathology nor in healthy controls with amyloid pathology. Additionally, the volume of the posterior of nucleus basalis of Meynert was significantly correlated with amyloid Aβ42/40 ratio in SCD but not in healthy controls. Conclusion Our results confirm that basal forebrain atrophy occurs early along the Alzheimer’s disease trajectory. The observed volume reduction of the cholinergic basal forebrain in Aβ-positive participants with subjective cognitive complains and the absence of any volume reductions in the Aβ-positive healthy controls suggests that these ‘subjective cognitive decline’ symptoms reflect progression from stage 1 (asymptomatic) to stage 2 (transitional cognitive impairment) of the Alzheimer’s continuum (according to the recent National Institute on Aging-Alzheimer’s Association Research Framework), revealing the beginning neurodegeneration on a macroscopic level.

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