Hana Horakova Markova

University Hospital Motol | FNMOTOL · Memory Clinic, Department of Neurology

Background There is initial evidence suggesting that biomarker neurogranin (Ng) may distinguish Alzheimer’s disease (AD) from other neurodegenerative diseases. Therefore, we assessed (a) the discriminant ability of cerebrospinal fluid (CSF) Ng levels to distinguish between AD and frontotemporal lobar degeneration (FTLD) pathology and between differ...

Defective mitophagy is consistently found in postmortem brain and iPSC-derived neurons from Alzheimer disease (AD) patients. However, there is a lack of extensive examination of mitophagy status in serum or cerebrospinal fluid (CSF), and the clinical potential of mitophagy biomarkers has not been tested. We quantified biomarkers of mitophagy/autoph...

Objective This study aims to evaluate the efficacy of the Uniform Data Set (UDS) 2 battery in distinguishing between individuals with mild cognitive impairment (MCI) attributable to Alzheimer’s disease (MCI-AD) and those with MCI due to other causes (MCI-nonAD), based on contemporary AT(N) biomarker criteria. Despite the implementation of the novel...

Impaired spatial navigation is early marker of Alzheimer’s disease (AD). We examined ability of self- and informant-reported navigation questionnaires to discriminate between clinically and biomarker-defined participants, and associations of questionnaires with navigation performance, regional brain atrophy, AD biomarkers, and biomarker status. 262...

Objective:We aimed to examine the profile and severity of mild behavioral impairment (MBI) in a sample of β-amyloid positive individuals with amnestic mild cognitive impairment (aMCI)compared to cognitively normal older adults (CN). Within aMCI, we further examined the potential influence of APOE and BDN Frisk genetic polymorphisms on MBI severity....

Background Mild behavioral impairment (MBI) has been commonly reported in early Alzheimer’s disease (AD) but rarely using biomarker-defined samples. It is also unclear whether genetic polymorphisms influence MBI in such individuals. We thus aimed to examine the association between the cognitive status of participants (amnestic mild cognitive impair...

Background Autophagy is a cellular self “garbage clearance ”system through which cells eliminate and recycle dysfunctional cytoplasmatic components, such as defective organelles and misfolded protein aggregates. Mitophagy is the sub‐type of autophagy that recognizes and degrades damaged or superfluous mitochondria to maintain cellular homeostasis....

Background Reduced removal of dysfunctional mitochondria has been implicated in the pathogenesis of many neurodegenerative diseases, including Alzheimer’s disease (AD) and Frontotemporal lobar degeneration (FTLD). Mitophagy is the main cellular pathway through which aberrant and aged mitochondria are removed. Impaired neuronal mitophagy triggers th...

Background Mild behavioral impairment (MBI) describes de novo emergent and persistent neuropsychiatric symptoms in older individuals. MBI is common in individuals with mild cognitive impairment (MCI), but self‐endorsed symptoms may not align with reports from informants. In this study, we explore the consistency between self‐ and informant‐rated ve...

Background Subjective cognitive complaints (SCC) in the elderly may represent an early cognitive marker of Alzheimer’s disease (AD). Currently, there is no recommended gold standard for evaluating SCC. In addition, available questionnaires were originally developed to identify individuals at later stages of AD. Based on previous research, we constr...

Background The Memory Binding Test (MBT) and Face‐Name Associative Memory Exam (FNAME‐12) are challenging tests based on relational memory binding paradigm. Recent studies support their sensitivity to subtle memory changes; however, their specificity to Alzheimer´s disease (AD) related memory deficit has not been studied. This study aimed to explor...

Progressive cognitive impairment is one of the major symptoms of idiopathic normal pressure hydrocephalus (iNPH), present in about 80% of patients. Together with gait disturbance and urinary incontinence, cognitive impairment constitutes a part of the clinical triad. Cognitive deficit is commonly accompanied by neuropsychiatric symptoms (NPS), obse...

Background: Impaired spatial navigation is an early marker of Alzheimer's disease (AD), but the utility of reported navigation abilities is poorly understood. We examined the ability of self- and informant-reported spatial navigation questionnaires to discriminate between clinically and AD biomarker-defined participants from the Czech Brain Aging S...

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. I...

Background Dementia syndrome is one of the most devastating conditions in older adults. As treatments to stop neurodegeneration become available, accurate and timely diagnosis will increase in importance. One issue is that cognitive performance sometimes does not match the corresponding level of neuropathology, affecting diagnostic accuracy. Cognit...

The risk of Alzheimer’s disease (AD) has a strong genetic component, also in the case of late-onset AD (LOAD). Attempts to sequence whole genome in large populations of subjects have identified only a few mutations common to most of the patients with AD. Targeting smaller well-characterized groups of subjects where specific genetic variations in se...

Background: Memory tests using controlled encoding and cued recall paradigm (CECR) have been shown to identify prodromal Alzheimer's disease (AD), but information about the effectiveness of CECR compared to other memory tests in predicting clinical progression is missing. Objective: The aim was to examine the predictive ability of a memory test...

Background: Older adults with subjective cognitive decline (SCD) are at an increased risk of progression to mild cognitive impairment (MCI) or dementia. However, few have examined the specific cognitive tests that are associated with progression. Objective: This study examined performance on 18 neuropsychological tests among participants with SC...

[This corrects the article DOI: 10.3389/fnagi.2021.643271.].

Innovative memory paradigms have been introduced to capture subtle memory changes in early Alzheimer’s disease (AD). We aimed to examine the associations between different indexes of the challenging Memory Binding Test (MBT) and hippocampal volume (HV) in a sample of individuals with subjective cognitive decline (SCD; n = 50), amnestic mild cogniti...

Aging and Alzheimer’s disease (AD), a major age-related disorder, are both characterized by inflammatory changes in the cerebrospinal fluid (CSF). The origin and the mechanisms underlying these inflammatory changes, however, remain poorly understood. Here, we report that aging elicits inflammatory changes in the CSF that become accentuated uniquely...

Background The apolipoprotein E ( APOE ) ɛ4 allele is associated with episodic memory deficits, less accurate spatial navigation and hippocampal atrophy in nondemented older adults. The brain‐derived neurotrophic factor ( BDNF ) Met allele may further worsen memory impairment and reduce hippocampal activation in APOE ɛ4 carriers but its role in APO...

Background: The hippocampus, entorhinal cortex (EC), and basal forebrain (BF) are among the earliest regions affected by Alzheimer’s disease (AD) pathology. They play an essential role in spatial pattern separation, a process critical for accurate discrimination between similar locations. Objective: We examined differences in spatial pattern separa...

Objectives Mild behavioral impairment (MBI) is a syndrome describing late-onset persistent neuropsychiatric symptoms (NPS) in non-demented older adults. Few studies to date have investigated the associations of MBI with structural brain changes. Our aim was to explore structural correlates of NPS in a non-demented memory clinic sample using the Mil...

Objective To compare cognitive phenotypes of participants with subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI), estimate progression to MCI/dementia by phenotype and assess classification error with machine learning. Method Dataset consisted of 163 participants with SCD and 282 participants with aMCI from the Czech...

Background: Identifying modifiable risk factors for cognitive decline can reduce burden of dementia. Objective: We examined whether homocysteine was associated with memory performance, mediated by entorhinal volume, hippocampal volume, total gray matter volume, or white matter lesions, and moderated by APOE ɛ4 allele, B vitamins, creatinine, tot...

A decline in cognitive functioning is part of physiological aging. Accelerated cognitive decline is frequently linked to pathological changes, mostly due to Alzheimer's Disease (AD), but is present also in Mild Cognitive Impairment (MCI) which is a predictor of transition to dementia. This review aims to summarize possible preventive biological and...

Dementia is arguably the most devastating condition of older adulthood with treatment options still elusive. Alzheimer’s is the most prevalent form of dementia where cognitive deficits relate strongly to underlying brain pathology. However, there exist cases in which cognitive performance does not match the corresponding level of neuropathology. At...

Background The apolipoprotein E ( APOE ) ɛ4 allele is associated with an increased risk of Alzheimer’s disease (AD), episodic memory deficits and less accurate spatial navigation in non‐demented older adults. The brain‐derived neurotrophic factor ( BDNF ) Val66Met polymorphism is also related to the increased risk of AD and more pronounced memory i...

Background Mild behavioral impairment (MBI) is a recently developed diagnostic concept describing late‐onset persistent neuropsychiatric symptoms (NPS) in older adults without dementia. Few studies to date investigated associations of MBI with structural brain changes. Our aim was to explore structural correlates of NPS in a non‐demented memory cli...

Background Worry associated with subjective cognitive decline (cognitive worry) in cognitively normal (CN) older adults has been established as a feature that increases the likelihood of preclinical Alzheimer´s disease (AD). Previously, it has been associated with a higher risk of progression to mild cognitive impairment and dementia. We aimed to e...

Background Brain‐derived neurotrophic factor (BDNF) is the neurotrophin well‐known for its role in neurogenesis, synaptic plasticity and enhancement of long‐term potentiation (LTP). Its precursor proBDNF exhibits opposite biological function – inhibits LTP and increases long‐term depression (LTD) in the brain. Altered proBDNF/BDNF ratio in favor of...

The results of neuropsychological tests may be distorted by patients who exaggerate cognitive deficits. Eighty-three patients with cognitive deficit [Amnestic Mild Cognitive Impairment (aMCI), n = 53; Alzheimer's disease (AD) dementia, n = 30], 44 healthy older adults (HA), and 30 simulators of AD (s-AD) underwent comprehensive neuropsychological a...

A decline in cognitive functioning is part of physiological aging. Accelerated cognitive decline is frequently linked to pathological changes, mostly due to Alzheimer’s Disease (AD), but is present also in Mild Cognitive Impairment (MCI) which is a predictor of transition to dementia. This review aims to summarize possible preventive biological and...

Background: The hippocampus, entorhinal cortex, and basal forebrain are among the first brain structures affected by Alzheimer's disease (AD). They play an essential role in spatial pattern separation, a process critical for accurate encoding of similar spatial information. Objective: Our aim was to examine spatial pattern separation and its ass...

Background and aims: Neuropsychiatric symptoms are a heterogeneous group of changes in personality and behavior that can be observed already in early stages of Alzheimer´s disease. Mild behavioral impairment (MBI) is a newly developed diagnostic category describing persistent changes in personality and behavior starting later in life. Based on thes...

Memory impairment has been considered as one of the earliest clinical hallmarks of Alzheimer’s disease. This paper summarizes recent progress in the assessment of memory impairment in predementia stages. New promising approaches of memory assessment include evaluation of longitudinal cognitive changes, assessment of long-term memory loss, evaluatio...

Apolipoprotein (APOE) ε4 is a well-known risk factor for late-onset Alzheimer disease (AD), but other AD-related gene polymorphisms might also be important, such as the polymorphism within the brain-derived neurotrophic factor (BDNF) gene. Carriage of BDNF Val66Met has been associated with faster cognitive decline and greater hippocampal atrophy in...

Background: Subjective cognitive complaints (SCCs) may represent an early cognitive marker of Alzheimer's disease (AD). There is a need to identify specific SCCs associated with an increased likelihood of underlying AD. Objective: Using the Questionnaire of Cognitive Complaints (QPC), we evaluated the pattern of SCCs in a clinical sample of non-...

Background: Cerebral microangiopathy in Alzheimer's disease (AD) causes chronic hypoperfusion and probably accelerates neurodegenerative changes. Objective: We hypothesize microvascular impairment could be present already in mild cognitive impairment (MCI) and can be revealed using transcranial color-coded sonography (TCCS) and the breath-holdin...

Introduction: Vascular brain changes and risk factors play a role in development and progres sion of Alzheimer's disease (AD). The primary aim of our study was to determin. The predictive value of neurosonological bio markers of cerebral microvasculature -resistance index (RI) and breath-holding index (BHI). The development AD dementia i. The older...

Background: Subjective cognitive complaints (SCCs) may be an early marker of prodromal Alzheimer's disease. Objectives: Using a 10-item yes/no SCCs questionnaire (Le Questionnaire de Plainte Cognitive [QPC]), we evaluated the prevalence and distribution of SCCs in cognitively healthy Czech older adults and examined total score and specific QPC i...

Patients with subjective cognitive decline (SCD) are at higher risk for conversion to dementia due to Alzheimer’s disease (AD). Semantic verbal fluency (SVF) seems to be impaired in the early stages of AD. The goal of the present study was to identify the discriminative potential of verbal fluency (VF) in patients with SCD to show if very early sig...

Aims: To find out whether neuropsychiatric comorbidity (comMCI) influences spatial navigation performance in amnestic mild cognitive impairment (aMCI). Methods: We recruited aMCI patients with (n = 21) and without (n = 21) neuropsychiatric comorbidity or alcohol abuse, matched for global cognitive impairment and cognitively healthy elderly parti...

RationaleDevelopment of new drugs for treatment of Alzheimer’s disease (AD) requires valid paradigms for testing their efficacy and sensitive tests validated in translational research. Objectives We present validation of a place-navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM), in comparable animal and human protocols....

Background: High plasma homocysteine (Hcy) level is related to higher risk of Alzheimer's disease (AD) and lower cognitive performance in older adults. Objective: To assess the association between plasma Hcy level and real-space navigation performance and the role of vascular risk and protective factors, APOE status, and white matter lesions (WM...

Cíle: Test Kresby jízdního kola (KJK) se v neuropsychologickém vyšetření používá pro hodnocení zrakově-prostorových a exekutivních funkcí. Zadání i vyhodnocení je jednoduché a časově nenáročné. Cílem této práce je prozkoumat psychometrické charakteristiky testu (reliabilita, validita), vliv demografi ckých proměn ných na skóry a popsat výsledky sou...

Objectives: The clock drawing test (CDT) is a commonly used brief cognitive measure. We evaluated diagnostic accuracy of subjective ratings of CDT by physicians (with/without specialty in cognitive neurology) and neuropsychologists in discriminating amnestic mild cognitive impairment (aMCI), Alzheimer's dementia (AD) and cognitively healthy older...

Aim: The aim of the study was to report normative data on letter (LF; letters K, P, S) and semantic fl uency (SF; animals and vegetables). Introduction: Verbal fl uency (VF) is one of the most frequently used neuropsychological methods for the assessment of cognitive performance in clinical and experimental neuropsychology. However, representative...

Introduction: The Clock Drawing Test is a frequently used cognitive screening test with several scoring systems in elderly populations. We compare simple and complex scoring systems and evaluate the usefulness of the combination of the Clock Drawing Test with the Mini-Mental State Examination to detect patients with mild cognitive impairment. Met...

The Bicycle Drawing Test (BDT) is used in neuropsychology to assess visuospatial and executive functions. Aim of this work is to examine its criterion validity in older patients with cognitive deficit. Seventy-two patients with cognitive deficits (mean age 73.5, SD=10.2) were administered BDT and other neuropsychological methods. 38 patients were d...

The Bicycle Drawing Test (BDT) is used in neuropsychological assessment to evaluate visuoconstructive and executive functions. It is simple to administer and does not take more than a couple of minutes. Aim of this study was to assess psychometric properties of BDT (inter-rater reliability, correlation with age, education, and gender), to establish...

Background and objective: Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among tests used to evaluate memory, verbal memory tests with controlled encoding and cued recall are believed to be specific for hippocampal impairment. The objective of this study was to...

The very long (VL) poly-T variant at rs10524523 ("523") of the TOMM40 gene may hasten the onset of late-onset Alzheimer's disease (LOAD) and induce more profound cognitive impairment compared with the short (S) poly-T variant. We examined the influence of TOMM40 "523" polymorphism on spatial navigation and its brain structural correlates. Participa...