Current Alzheimer Research - Volume 15, Issue 3, 2018

Objective: The present study analyzes the age-related differences in map learning between young and normally-aging young-old and old-old adults in relation to individual visuo-spatial factors to specify which aspects of spatial learning are susceptible to aging. Methods: Forty young, 40 young-old and 40 old-old participants performed a series of tasks to assess their visuo-spatial working memory (VSWM) and visuo-spatial (rotation) abilities, then they studied a map. To test their recall, they graphically reproduced the map in a freehand drawing, then performed a sketch map task (which involved placing a list of landmarks on a blank layout of the map) and a pointing task (adopting aligned and counter-aligned imaginary positions). Results: The results showed that age-related differences depend on the type of recall task performed: in the pointing and freehand map-drawing tasks, the young-old and old-old performed worse than the young adults; but in the sketch map task, the young-old performed as well as the young adults and only the old-old's performance was worse than that of the other two age groups. Concerning the role of individual factors, VSWM and rotation abilities were found strongly involved in the pointing task (especially for counter-aligned pointing) and the freehand map-drawing task. Conclusion: Overall, these results suggest that different factors related to spatial (map) learning explain age-related differences in normal aging. The implications of the present results in normal and pathological aging, and for the purposes of clinical assessments and interventions, are discussed.

Background: Great effort has been put into developing simple and feasible tools capable to detect Alzheimer's disease (AD) in its early clinical stage. Spatial navigation impairment occurs very early in AD and is detectable even in the stage of mild cognitive impairment (MCI). Objective: The aim was to describe the frequency of self-reported spatial navigation complaints in patients with subjective cognitive decline (SCD), amnestic and non-amnestic MCI (aMCI, naMCI) and AD dementia and to assess whether a simple questionnaire based on these complaints may be used to detect early AD. Method: In total 184 subjects: patients with aMCI (n=61), naMCI (n=27), SCD (n=63), dementia due to AD (n=20) and normal controls (n=13) were recruited. The subjects underwent neuropsychological examination and were administered a questionnaire addressing spatial navigation complaints. Responses to the 15 items questionnaire were scaled into four categories (no, minor, moderate and major complaints). Results: 55% of patients with aMCI, 64% with naMCI, 68% with SCD and 72% with AD complained about their spatial navigation. 38-61% of these complaints were moderate or major. Only 33% normal controls expressed complaints and none was ranked as moderate or major. The SCD, aMCI and AD dementia patients were more likely to express complaints than normal controls (p's<0.050) after adjusting for age, education, sex, depressive symptoms (OR for SCD=4.00, aMCI=3.90, AD dementia=7.02) or anxiety (OR for SCD=3.59, aMCI=3.64, AD dementia=6.41). Conclusion: Spatial navigation complaints are a frequent symptom not only in AD, but also in SCD and aMCI and can potentially be detected by a simple and inexpensive questionnaire.

Objective: Deficits in egocentric (subject-to-object) and allocentric (object-to-object) spatial representations, with a mainly allocentric impairment, characterize the first stages of the Alzheimer's disease (AD). Methods: To identify early cognitive signs of AD conversion, some studies focused on amnestic-Mild Cognitive Impairment (aMCI) by reporting alterations in both reference frames, especially the allocentric ones. However, spatial environments in which we move need the cooperation of both reference frames. Such cooperating processes imply that we constantly switch from allocentric to egocentric frames and vice versa. This raises the question of whether alterations of switching abilities might also characterize an early cognitive marker of AD, potentially suitable to detect the conversion from aMCI to dementia. Here, we compared AD and aMCI patients with Normal Controls (NC) on the Ego-Allo- Switching spatial memory task. The task assessed the capacity to use switching (Ego-Allo, Allo-Ego) and non-switching (Ego-Ego, Allo-Allo) verbal judgments about relative distances between memorized stimuli. Results: The novel finding of this study is the neat impairment shown by aMCI and AD in switching from allocentric to egocentric reference frames. Interestingly, in aMCI when the first reference frame was egocentric, the allocentric deficit appeared attenuated. Conclusion: This led us to conclude that allocentric deficits are not always clinically detectable in aMCI since the impairments could be masked when the first reference frame was body-centred. Alongside, AD and aMCI also revealed allocentric deficits in the non-switching condition. These findings suggest that switching alterations would emerge from impairments in hippocampal and posteromedial areas and from concurrent dysregulations in the locus coeruleus-noradrenaline system or pre-frontal cortex.

Background: Recently, efforts have been made to combine complementary perspectives in the assessment of Alzheimer type dementia. Of particular interest is the definition of the fingerprints of an early stage of the disease known as Mild Cognitive Impairment or prodromal Alzheimer's Disease. Machine learning approaches have been shown to be extremely suitable for the implementation of such a combination. Methods: In the present pilot study we combined the machine learning approach with structural magnetic resonance imaging and cognitive test assessments to classify a small cohort of 11 healthy participants and 11 patients experiencing Mild Cognitive Impairment. Cognitive assessment included a battery of standardised tests and a battery of experimental visuospatial memory tests. Correct classification was achieved in 100% of the participants, suggesting that the combination of neuroimaging with more complex cognitive tests is suitable for early detection of Alzheimer Disease. Results: In particular, the results highlighted the importance of the experimental visuospatial memory test battery in the efficiency of classification, suggesting that the high-level brain computational framework underpinning the participant's performance in these ecological tests may represent a “natural filter” in the exploration of cognitive patterns of information able to identify early signs of the disease.

Objective: Autonomy in patients with Alzheimer's disease (AD) in daily life depends on the preservation of neurocognitive and motor abilities, which decline over time. So far, very few studies have investigated motor representations and their contribution to perception and cognition in AD. Methods: In the present study, we compared the performance of AD patients to age-matched healthy participants in perceptual and cognitive tasks involving motor imagery. Experiment 1 tested explicit motor and visual imagery through an imagined movement task. Experiment 2 tested body-centred implicit motor imagery through a mental rotation of visual hand task. Finally, Experiment 3 tested object-centred implicit motor imagery through a reachability judgment task. Results: The results showed that, compared to age-matched controls, conscious imagination of a body movement or the movement of a visual stimulus was much longer in AD patients, with no specific difficulty in the motor condition (Experiment 1). Furthermore, response time in AD patients was strongly affected by the angle of rotation of the visual stimuli in the mental rotation of hand task (Experiment 2). Likewise, response time in AD patients increased substantially in the reachability judgment task, but predominantly for stimuli located at the boundary of peripersonal space (Experiment 3). Conclusion: As a whole, the data suggested a decline in AD of implicit, but not explicit, motor imagery capacities affecting processing time, but not performance accuracy, in motor-related perceptual and cognitive tasks.

Background: It has been shown that theta (6-10 Hz) and delta (1-6 Hz) ongoing electroencephalographic (EEG) rhythms revealed variations in the cortical arousal in C57 Wild Type (WT) mice during cage exploration (active condition) compared to awake quiet behavior (passive condition; IMI PharmaCog project, www.pharmacog.eu). Objective: The objective was to test if these EEG rhythms might be abnormal in old PDAPP mice modeling Alzheimer's disease (AD) with a hAPP Indiana V717F mutation (They show abnormal neural transmission, cognitive deficits, and brain accumulation of Aβ1-42). Methods: Ongoing EEG rhythms were recorded by a frontoparietal bipolar channel in 15 PDAPP and 23 WT C57 male mice (mean age of 22.8 months ±0.4 and 0.3 standard error, respectively). EEG absolute power (density) was calculated. Frequency and amplitude of individual delta and theta frequency (IDF and ITF) peaks were considered during passive and active states in the wakefulness. Results: Compared with the WT group, the PDAPP group showed higher frequency of the IDF during the passive condition and lower frequency of the ITF during the active state. Furthermore, the WT but not PDAPP group showed significant changes in the frontoparietal EEG power (IDF, ITF) during active over passive state. Conclusion: PDAPP mice were characterized by less changes in the brain arousal during an active state as revealed by frontoparietal EEG rhythms. Future studies will have to cross-validate the present results on large animal groups, clarify the neurophysiological underpinning of the effect, and test if the disease modifying drugs against AD amyloidosis normalize those candiate EEG biomarkers in PDAPP mice

Background: The study aims to determine the spatiotemporal gait parameters and/or their combination(s) that best differentiate between cognitively healthy individuals (CHI), patients with mild cognitive impairment (MCI) and those with mild and moderate dementia, regardless of the etiology of cognitive impairment. Methods: A total of 2099 participants (1015 CHI, 478 patients with MCI, 331 patients with mild dementia and 275 with moderate dementia) were selected from the intercontinental “Gait, cOgnitiOn & Decline” (GOOD) initiative, which merged different databases from seven cross-sectional studies. Mean values and coefficients of variation (CoV) of spatiotemporal gait parameters were recorded during usual walking with the GAITRite® system. Results: The severity of cognitive impairment was associated with worse performance on all gait parameters. Stride velocity had the strongest association with cognitive impairment, regardless of cognitive status. High mean value and CoV of stride length characterized moderate dementia, whereas increased CoV of stride time was specific to MCI status. Conclusion: The findings support the existence of specific cognitive impairment-related gait disturbances with differences related to stages of cognitive impairment, which may be used to screen individuals with cognitive impairment.

Objective: Alzheimer's disease (AD), the most important progressive neurodegenerative disorder, is characterized by cognitive and behavioral disabilities. Nowadays, tau, as a microtubuleassociated protein and a principle neuropathological hallmark of AD, provides us a neoteric perspective to explore further aetiopathogenesis and therapeutic strategy. The hyperphosphorylation and abnormal aggregation of tau, combined with its decreased clearance, form neurofibrillary tangles (NFTs) and exert neurotoxicity in AD. Methods: Recent investigations aim to prevent the deposition of NFT and accelerate the clearance of NFT. Intriguingly, immunization strategies targeting tau effectively ameliorates the tau-associated pathology in AD. In addition, modified therapies targeting tau should be regarded as a potential way to treat AD. These progresses open new avenues for AD. Conclusion: Here, we review the recent literature of potential mechanisms of the tau in AD and discuss the modified therapeutic strategies for AD.