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Navigation difficulties early sign of Alzheimer's

  • A mobile phone game designed to test spatial navigation skills (Sea Hero Quest) has found that performance can distinguish APOE4 carriers from non-carriers.
  • Preliminary findings from a long-term study indicate that middle-aged adults with close relatives with Alzheimer's did worse on a test that measured their ability to visualise their position, and tended to have a smaller hippocampus.
  • A small study found that increasing difficulties with building cognitive maps of new surroundings was linked to Alzheimer's biomarkers. Difficulties in learning a new route appeared later, among those with early Alzheimer's.

Mobile game detects Alzheimer's risk

A specially designed mobile phone game called Sea Hero Quest has found that gaming data can distinguish between those people who are genetically at risk of developing Alzheimer's disease ond those who are not. The game is designed to test spatial navigation skills — one of the first cognitive areas affected in Alzheimer's.

A standard memory and thinking test could not distinguish between the risk and non-risk groups.

Gaming data was taken from 27,108 UK players aged 50-75. This benchmark data was then compared with 60 people who had been genetically tested, of whom about half carried the APOE4 gene. The gene tested individuals were matched for age, gender, education and nationality with the benchmark cohort.

Previous findings from Sea Hero Quest data have shown that people in different countries and populations navigate differently, but this study shows that APOE4 carriers took less efficient (i.e., longer) routes to checkpoint goals. The difference in performance between carriers and non-carriers was particularly pronounced where the space to navigate was large and open.

https://www.eurekalert.org/pub_releases/2019-04/uoea-tmg042419.php

Getting lost may be the first sign of Alzheimer’s

Preliminary findings from a long-term UK study indicate that middle-aged adults (41-59) with close relatives with Alzheimer's did worse on a test that measured their ability to visualise their position. They also tended to have a small hippocampus.

The Four Mountains test involves showing people a picture of a mountain and asking them to identify it in a selection of four other landscapes.

https://www.theguardian.com/society/2017/may/06/getting-lost-may-be-first-sign-of-alzheimers

Building mental maps precedes route navigation problems

A study involving 71 older adults found that increasing difficulties with building cognitive maps of new surroundings was associated with the development of Alzheimer's biomarkers. Difficulties in learning a new route were not evident at this stage, but appeared later, among those with early Alzheimer's.

The computer task involved navigating a virtual maze consisting of a series of interconnected hallways with four wallpaper patterns and 20 landmarks. Participants were tested on two navigation skills: how well they could learn and follow a pre-set route, and how well they could form and use a cognitive map of the environment. Participants were given 20 minutes to either learn a specified route, or to study and explore the maze with a navigation joystick. They were then tested on their ability to recreate the route or find their way to specific landmarks in the environment.

Humans generally find their way using two distinct forms of spatial representation and navigation: egocentric navigation, in which people rely on past knowledge to follow well-worn routes, moving from one landmark to another, and allocentric navigation, in which people become familiar with their big picture surroundings and create a mental map of existing landmarks, allowing them to plot best available routes and find shortcuts to new destinations. Allocentric navigation relies on the hippocampus, while egocentric navigation is more closely associated with a brain region called the caudate.

Those with cerebrospinal markers for Alzheimer’s but no symptoms, had significant difficulties only when they had to form a cognitive map (that is, with hippocampal allocentric navigation processes). However, additional training did enable them to eventually learn the cognitive map.

The researchers suggest that preclinical Alzheimer’s disease is characterized by hippocampal atrophy and associated cognitive mapping difficulties, and then, (if) the disease progresses, cognitive mapping deficits worsen, the caudate becomes involved, leading to route learning deficits.

Participants included 42 who were cognitively healthy and had no cerebrospinal fluid markers for Alzheimer’s, 13 cognitively normal individuals who had the biomarkers, and 16 with early Alzheimer’s.

http://www.futurity.org/alzheimers-maps-nativation-1143342-2/

Reference: 

[4415] Coughlan, G., Coutrot A., Khondoker M., Minihane A-M., Spiers H., & Hornberger M.
(2019).  Toward personalized cognitive diagnostics of at-genetic-risk Alzheimer’s disease.
Proceedings of the National Academy of Sciences. 116(19), 9285 - 9292.

[4446] Ritchie, K., Carrière I., Su L., O'Brien J. T., Lovestone S., Wells K., et al.
(2017).  The midlife cognitive profiles of adults at high risk of late-onset Alzheimer's disease: The PREVENT study.
Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 13(10), 1089 - 1097.

[4445] Allison, S. L., Fagan A. M., Morris J. C., & Head D.
(2016).  Spatial Navigation in Preclinical Alzheimer’s Disease.
Journal of Alzheimer's Disease. 52(1), 77 - 90.

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Males' superior spatial ability probably not an evolutionary adaptation

Evidence against an evolutionary explanation for male superiority in spatial ability coves from a review of 35 studies covering 11 species: cuttlefish, deer mice, horses, humans, laboratory mice, meadow voles, pine voles, prairie voles, rats, rhesus macaques and talastuco-tucos (a type of burrowing rodent). In eight species, males demonstrated moderately superior spatial skills to their female counterparts, regardless of the size of their territories or the extent to which males ranged farther than females of the same species.

03/2013

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Latest London taxi driver study shows brain changes driven by learning

January, 2012
  • A comparison of the brains of London taxi drivers before and after their lengthy training shows clearly that the increase in hippocampal gray matter develops with training, but this may come at the expense of other brain functions.

The evidence that adult brains could grow new neurons was a game-changer, and has spawned all manner of products to try and stimulate such neurogenesis, to help fight back against age-related cognitive decline and even dementia. An important study in the evidence for the role of experience and training in growing new neurons was Maguire’s celebrated study of London taxi drivers, back in 2000.

The small study, involving 16 male, right-handed taxi drivers with an average experience of 14.3 years (range 1.5 to 42 years), found that the taxi drivers had significantly more grey matter (neurons) in the posterior hippocampus than matched controls, while the controls showed relatively more grey matter in the anterior hippocampus. Overall, these balanced out, so that the volume of the hippocampus as a whole wasn’t different for the two groups. The volume in the right posterior hippocampus correlated with the amount of experience the driver had (the correlation remained after age was accounted for).

The posterior hippocampus is preferentially involved in spatial navigation. The fact that only the right posterior hippocampus showed an experience-linked increase suggests that the right and left posterior hippocampi are involved in spatial navigation in different ways. The decrease in anterior volume suggests that the need to store increasingly detailed spatial maps brings about a reorganization of the hippocampus.

But (although the experience-related correlation is certainly indicative) it could be that those who manage to become licensed taxi drivers in London are those who have some innate advantage, evidenced in a more developed posterior hippocampus. Only around half of those who go through the strenuous training program succeed in qualifying — London taxi drivers are unique in the world for being required to pass through a lengthy training period and pass stringent exams, demonstrating their knowledge of London’s 25,000 streets and their idiosyncratic layout, plus 20,000 landmarks.

In this new study, Maguire and her colleague made a more direct test of this question. 79 trainee taxi drivers and 31 controls took cognitive tests and had their brains scanned at two time points: at the beginning of training, and 3-4 years later. Of the 79 would-be taxi drivers, only 39 qualified, giving the researchers three groups to compare.

There were no differences in cognitive performance or brain scans between the three groups at time 1 (before training). At time 2 however, when the trainees had either passed the test or failed to acquire the Knowledge, those trainees that qualified had significantly more gray matter in the posterior hippocampus than they had had previously. There was no change in those who failed to qualify or in the controls.

Unsurprisingly, both qualified and non-qualified trainees were significantly better at judging the spatial relations between London landmarks than the control group. However, qualified trainees – but not the trainees who failed to qualify – were worse than the other groups at recalling a complex visual figure after 30 minutes (see here for an example of such a figure). Such a finding replicates previous findings of London taxi drivers. In other words, their improvement in spatial memory as it pertains to London seems to have come at a cost.

Interestingly, there was no detectable difference in the structure of the anterior hippocampus, suggesting that these changes develop later, in response to changes in the posterior hippocampus. However, the poorer performance on the complex figure test may be an early sign of changes in the anterior hippocampus that are not yet measurable in a MRI.

The ‘Knowledge’, as it is known, provides a lovely real-world example of expertise. Unlike most other examples of expertise development (e.g. music, chess), it is largely unaffected by childhood experience (there may be some London taxi drivers who began deliberately working on their knowledge of London streets in childhood, but it is surely not common!); it is developed through a training program over a limited time period common to all participants; and its participants are of average IQ and education (average school-leaving age was around 16.7 years for all groups; average verbal IQ was around or just below 100).

So what underlies this development of the posterior hippocampus? If the qualified and non-qualified trainees were comparable in education and IQ, what determined whether a trainee would ‘build up’ his hippocampus and pass the exams? The obvious answer is hard work / dedication, and this is borne out by the fact that, although the two groups were similar in the length of their training period, those who qualified spent significantly more time training every week (an average of 34.5 hours a week vs 16.7 hours). Those who qualified also attended far more tests (an average of 15.6 vs 2.6).

While neurogenesis is probably involved in this growth within the posterior hippocampus, it is also possible that growth reflects increases in the number of connections, or in the number of glia. Most probably (I think), all are involved.

There are two important points to take away from this study. One is its clear demonstration that training can produce measurable changes in a brain region. The other is the indication that this development may come at the expense of other regions (and functions).

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Adolescent binge drinking can damage spatial working memory

August, 2011
  • This study finds that adolescent females are particularly vulnerable to the effects of binge drinking, and points to specific changes in brain activation patterns seen in binge drinkers.

Binge drinking occurs most frequently among young people, and there has been concern that consequences will be especially severe if the brain is still developing, as it is in adolescence. Because of the fact that it is only some parts of the brain — most crucially the prefrontal cortex and the hippocampus — that are still developing, it makes sense that only some functions will be affected.

I recently reported on a finding that binge drinking university students, performed more poorly on tests of verbal memory, but not on a test of visual memory. A new study looks at another function: spatial working memory. This task involves the hippocampus, and animal research has indicated that this region may be especially vulnerable to binge drinking. Spatial working memory is involved in such activities as driving, figural reasoning, sports, and navigation.

The study involved 95 adolescents (aged 16-19) from San Diego-area public schools: 40 binge drinking (27 males, 13 females) and 55 control (31 males, 24 females). Brain scans while performing a spatial working memory task revealed that there were significant gender differences in brain activation patterns for those who engaged in binge drinking. Specifically, in eight regions spanning the frontal cortex, anterior cingulate, temporal cortex, and cerebellum, female binge drinkers showed less activation than female controls, while male bingers exhibited greater activation than male controls. For female binge drinkers, less activation was associated with poorer sustained attention and working memory performances, while for male binge drinkers, greater activation was linked to better spatial performance.

The differences between male binge drinkers and controls were smaller than that seen in the female groups, suggesting that female teens may be particularly vulnerable. This is not the first study to find a gender difference in the brains’ response to excess alcohol. In this case it may have to do, at least partly, with differences in maturity — female brains mature earlier than males’.

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Old bees' memory fades too

November, 2010
  • New research shows that many old bees, like many older humans, have trouble replacing out-of-date knowledge with new memories.

I love cognitive studies on bees. The whole notion that those teeny-tiny brains are capable of the navigation and communication feats bees demonstrate is so wonderful. Now a new study finds that, just like us, aging bees find it hard to remember the location of a new home.

The study builds on early lab research that demonstrated that old bees find it harder to learn floral odors. In this new study, researchers trained bees to a new nest box while their former nest was closed off. Groups composed of mature and old bees were given several days in which to learn the new home location and to extinguish the bees' memory of their unusable former nest box. The new home was then disassembled, and groups of mixed-age bees were given three alternative nest locations to choose from (including the former nest box). Some old bees (those with symptoms of senescence) preferentially went to the former nest site, despite the experience that should have told them that it was unusable.

The findings demonstrate that memory problems and increasing inflexibility with age are not problems confined to mammals.

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Connection between navigation, object location, & autobiographical memory

January, 2010
  • The existence of specialized neurons involved in spatial memory has now been found in humans, and appear to also help with object location and autobiographical memory.

Rodent studies have demonstrated the existence of specialized neurons involved in spatial memory. These ‘grid cells’ represent where an animal is located within its environment, firing in patterns that show up as geometrically regular, triangular grids when plotted on a map of a navigated surface. Now for the first time, evidence for these cells has been found in humans. Moreover, those with the clearest signs of grid cells performed best in a virtual reality spatial memory task, suggesting that the grid cells help us to remember the locations of objects. These cells, located particularly in the entorhinal cortex, are also critical for autobiographical memory, and are amongst the first to be affected by Alzheimer's disease, perhaps explaining why getting lost is one of the most common early symptoms.

Reference: 

[378] Doeller, C. F., Barry C., & Burgess N.
(2010).  Evidence for grid cells in a human memory network.
Nature. 463(7281), 657 - 661.

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Memory replay not as simple as thought

March, 2010
  • Several reports have come out in recent years on how recent events replay in the hippocampus, a process thought to be crucial for creating long-term memories. Now a rat study suggests that these replays are not merely echoes of past events, but may include possible events that never happened.

Several reports have come out in recent years on how recent events replay in the hippocampus, a process thought to be crucial for creating long-term memories. Now a rat study suggests that these replays are not merely echoes of past events, but a dynamic process aimed at improving decision-making. Rather than being solely replays of recent or frequent paths through the maze, the replays were often paths that the rats had rarely taken or, in some cases, had never taken, as if the rats were trying to build maps to help them make better navigation decisions.

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