Jakub Hort

Spatial navigation deficit in amnestic mild cognitive impairment

Patients with Alzheimers disease (AD) frequently have difficulties with spatial orientation in their day-to-day life. Although AD is typically preceded by amnestic mild cognitive impairment (MCI), spatial navigation has not yet been studied in MCI. Sixty-five patients were divided into five groups: probable AD (n = 21); MCI, further classified as amnestic MCI single domain (n = 11); amnestic MCI multiple domain (n = 18), or nonamnestic MCI (n = 7), and subjective memory complaints (n = 8). These patients, together with a group of healthy control subjects (n = 26), were tested by using a four-subtests task that required them to locate an invisible goal inside a circular arena. Each subtest began with an overhead view of the arena showed on a computer monitor. This was followed by a real navigation inside of the actual space, an enclosed arena 2.9 m in diameter. Depending on the subtest, the subjects could use the starting position and/or cues on the wall for navigation. The subtests thus were focused on allocentric and egocentric navigation. The AD group and amnestic MCI multiple-domain group were impaired in all subtests. The amnestic MCI single-domain group was impaired significantly in subtests focused on allocentric orientation and at the beginning of the real space egocentric subtest, suggesting impaired memory for allocentric and real space configurations. Our results suggest that spatial navigation impairment occurs early in the development of AD and can be used for monitoring of the disease progression or for evaluation of presymptomiatic AD.

EFNS-ENS Guidelines on the diagnosis and management of disorders associated with dementia

The last version of the EFNS dementia guidelines is from 2007. In 2010, the revised guidelines for Alzheimers disease (AD) were published. The current guidelines involve the revision of the dementia syndromes outside of AD, notably vascular cognitive impairment, frontotemporal lobar degeneration, dementia with Lewy bodies, corticobasal syndrome, progressive supranuclear palsy, Parkinsons disease dementia, Huntingtons disease, prion diseases, normal‐pressure hydrocephalus, limbic encephalitis and other toxic and metabolic disorders. The aim is to present a peer‐reviewed evidence‐based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists and other specialist physicians responsible for the care of patients with dementing disorders. It represents a statement of minimum desirable standards for practice guidance.

Spatial navigation testing discriminates two types of amnestic mild cognitive impairment

The hippocampus is essential for consolidation of declarative information and spatial navigation. Alzheimers disease (AD) diagnosis tends to be preceded by a long prodromal period and mild cognitive impairment (MCI). Our goal was to test whether amnestic MCI comprises two different subgroups, with hippocampal and non-hippocampal memory impairment, that vary with respect to spatial navigation ability. A total of 52 patients were classified into two subgroups: non-amnestic MCI (naMCI) (n=10) and amnestic MCI (aMCI) (n=42). The aMCI subgroup was further stratified into memory impairment of hippocampal type-hippocampal aMCI (HaMCI) (n=10) (potential preclinical AD) and isolated retrieval impairment-non-hippocampal (NHaMCI) (n=32). Results were compared to control (n=28) and AD (n=21) groups. We used the Hidden Goal Task, a human analogue of the Morris Water Maze, to examine spatial navigation either dependent (egocentric) or independent of individuals position (allocentric). Overall, the HaMCI group performed poorer on spatial navigation than the NHaMCI group, especially in the latter trials when the HaMCI group exhibited limited capacity to learn and the NHaMCI group exhibited a learning effect. Finally, the HaMCI group performed almost identically as the AD group. Spatial navigation deficit is particularly pronounced in individuals with hippocampus-related memory impairment and may signal preclinical AD.

Cognitive Functions After Pilocarpine‐Induced Status Epilepticus: Changes During Silent Period Precede Appearance of Spontaneous Recurrent Seizures

Summary: Purpose: To study the possible relation between spontaneous recurrent seizures (SRS) and the derangement of cognitive memory.

Spatial navigation impairment is proportional to right hippocampal volume

Cognitive deficits in older adults attributable to Alzheimers disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (β = −0.62, P < 0.001) and virtual (β = −0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P ≤ 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present.

Use of cerebrospinal fluid biomarkers in diagnosis of dementia across Europe

Background and purpose:  Cerebrospinal fluid (CSF) biomarkers have been reported to be useful in dementia diagnosis. Not much is known about their use in clinical practice in Europe.

Effect of Meditation on Cognitive Functions in Context of Aging and Neurodegenerative Diseases

Effect of different meditation practices on various aspects of mental and physical health is receiving growing attention. The present paper reviews evidence on the effects of several mediation practices on cognitive functions in the context of aging and neurodegenerative diseases. The effect of meditation in this area is still poorly explored. Seven studies were detected through the databases search, which explores the effect of meditation on attention, memory, executive functions, and other miscellaneous measures of cognition in a sample of older people and people suffering from neurodegenerative diseases. Overall, reviewed studies suggested a positive effect of meditation techniques, particularly in the area of attention, as well as memory, verbal fluency, and cognitive flexibility. These findings are discussed in the context of MRI studies suggesting structural correlates of the effects. Meditation can be a potentially suitable non-pharmacological intervention aimed at the prevention of cognitive decline in the elderly. However, the conclusions of these studies are limited by their methodological flaws and differences of various types of meditation techniques. Further research in this direction could help to verify the validity of the findings and clarify the problematic aspects.

Blood markers of oxidative stress in Alzheimer's disease.

Alzheimer′s disease (AD) represents a highly common form of dementia, but can be diagnosed in the earlier stages before dementia onset. Early diagnosis is crucial for successful therapeutic intervention. The introduction of new diagnostic biomarkers for AD is aimed at detecting underlying brain pathology. These biomarkers reflect structural or biochemical changes related to AD. Examination of cerebrospinal fluid has many drawbacks; therefore, the search for sensitive and specific blood markers is ongoing. Investigation is mainly focused on upstream processes, among which oxidative stress in the brain is of particular interest. Products of oxidative stress may diffuse into the blood and evaluating them can contribute to diagnosis of AD. However, results of blood oxidative stress markers are not consistent among various studies, as documented in this review. To find a specific biochemical marker for AD, we should concentrate on specific metabolic products formed in the brain. Specific fluorescent intermediates of brain lipid peroxidation may represent such candidates as the composition of brain phospholipids is unique. They are small lipophilic molecules and can diffuse into the blood stream, where they can then be detected. We propose that these fluorescent products are potential candidates for blood biomarkers of AD.

Spatial navigation—a unique window into physiological and pathological aging

Spatial navigation is a skill of determining and maintaining a trajectory from one place to another. Mild progressive decline of spatial navigation develops gradually during the course of physiological ageing. Nevertheless, severe spatial navigation deficit can be the first sign of incipient Alzheimers disease (AD), occurring in the stage of mild cognitive impairment (MCI), preceding the development of a full blown dementia. Patients with amnestic MCI, especially those with the hippocampal type of amnestic syndrome, are at very high risk of AD. These patients present with the same pattern of spatial navigation impairment as do the patients with mild AD. Spatial navigation testing of elderly as well as computer tests developed for routine clinical use thus represents a possibility for further investigation of this cognitive domain, but most of all, an opportunity for making early diagnosis of AD.

Spatial Navigation and APOE in Amnestic Mild Cognitive Impairment

Background: The effect of APOE Ε4 allele (Ε4) on spatial navigation in amnestic mild cognitive impairment (aMCI) is unknown. Objective: Our purpose was to examine the characteristics of spatial navigation impairment in Ε4-positive (Ε4+) and Ε4-negative (Ε4–) aMCI subgroups. Methods: Blood samples were collected to determine the APOE genotype. A total of 34 aMCI patients were stratified into aMCI-Ε4– (n = 23) and aMCI-Ε4+ (n = 11) groups. Control (n = 28) and mild Alzheimer’s disease (AD; n = 16) groups were also used. We used a human analogue of the Morris water maze (enclosed arena 2.9 m in diameter) to examine body-centered (egocentric) and world-centered (allocentric) spatial navigation. Results: The aMCI-Ε4+ group performed poorer on spatial navigation than the aMCI-Ε4– group in both egocentric and allocentric tasks even though these 2 groups did not differ in global cognitive functioning or neuropsychological tests. The aMCI-Ε4+ and mild AD groups performed similarly on all Morris Water Maze tasks and were outperformed by the aMCI-Ε4– group, which also resembled the control group in performance on the egocentric tasks. The aMCI groups showed poor spatial navigation learning regardless of their Ε4 positivity. Conclusion: We found more profound deficits in spatial navigation in aMCI-Ε4+ relative to aMCI-Ε4– patients. The aMCI-Ε4+ group resembled the mild AD group in spatial navigation performance. Although the Ε4 genotype was indicative of spatial navigation performance, it was not indicative of the aMCI patients’ ability to learn the tasks. Spatial navigation testing represents a promising area with respect to identifying individuals at higher risk for AD among the heterogeneous MCI population.