early markers

Alzheimer's produces early brain atrophy

  • A large study finds those who go on to develop Alzheimer's show atrophy of the hippocampus before age 40, and in the amygdala around age 40.

Brain scans from over 4,000 people, across the age range (9 months to 94 years) and including 1,385 Alzheimer's patients, has revealed an early divergence between those who go on to develop Alzheimer’s and those who age normally. This divergence is seen in early atrophy of the hippocampus before age 40, and in the amygdala around age 40.






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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.


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.


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.


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.



[4415] Coughlan, G., Coutrot A., Khondoker M., Minihane A-M., Spiers H., & Hornberger M.
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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Anxiety linked to rising amyloid-beta levels

  • A study found an association in healthy older adults between higher amyloid beta levels and worsening anxiety.








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New retinal test for early Alzheimer's disease

  • A new test can quickly detect reduced blood capillaries in the back of the eye that are an early indication of Alzheimer's, and shows that it can help distinguish Alzheimer's from MCI.

A study has shown new technology can quickly and non-invasively detect reduced blood capillaries in the back of the eye that are an early indication of Alzheimer's. It also shows that these signs can help distinguish between Alzheimer's and MCI.

The study compared the retinas of 39 Alzheimer's patients, 37 people with MCI, and 133 cognitively healthy people. The Alzheimer's group had loss of small retinal blood vessels at the back of the eye and a specific layer of the retina was thinner when compared to people with MCI and healthy people. The differences in density were statistically significant after researchers controlled for factors including age and sex.

It's been known that patients with Alzheimer's had decreased retinal blood flow and vessel density but it had not been known if these changes were also present in individuals with early Alzheimer's or aMCI.

Larger datasets are required to validate the marker.






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Brain changes linked with Alzheimer's years before symptoms appear

  • A long-running study found subtle cognitive deficits evident 11-15 years before clear impairment, as were changes in tau protein.





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Difficulties identifying odors early sign of dementia

  • A large study found that most of those who were very poor at identifying common odors developed dementia within 5 years.
  • A study of older adults with a parent who had Alzheimer's found that those who were poorest at identifying odors showed the most Alzheimer's biomarkers.
  • A largish study found that poorer odor identification in older adults (average age 80) )was associated with a transition to dementia and with cognitive decline.
  • An animal study found olfactory dysfunction precedes cognitive problems, and relates amyloid-beta protein in the olfactory epithelium.
  • A large 13-year study found that a poor sense of smell was linked to a greater risk of death within 10 years, and of death from dementia and Parkinson’s disease in particular.

A long-term study of nearly 3,000 older adults (57-85) has found that those who couldn’t identify at least four out of five common odors were more than twice as likely as those with a normal sense of smell to develop dementia within five years.

Of the participants, some 14% could name just three out of five, 5% could identify only two scents, 2% just one, and 1% couldn’t identify a single smell.

Five years after the smell test, almost all of the study subjects who were unable to name a single scent had been diagnosed with dementia, and nearly 80% of those who provided only one or two correct answers.

The test involved a well-validated tool known as "Sniffin'Sticks." The five odors, in order of increasing difficulty, are peppermint, fish, orange, rose and leather.


A study involving nearly 300 older adults (average age 63) who had a parent with Alzheimer’s has found that those with the most difficulty in identifying odors were those in whom Alzheimer's biomarkers were most evident.

Sense of smell was assessed using multiple choice scratch-and-sniff tests to identify scents as varied as bubble gum, gasoline or the smell of a lemon. A hundred of the participants had regular lumbar punctures to measure the Alzheimer's biomarkers in the cerebrospinal fluid.


A seven-year study involving a multi-ethnic (34% White, 30% African-American, 36% Hispanic) sample of 757 healthy older adults (average age 80.7) found that lower odor identification scores on UPSIT were significantly associated with both the transition to dementia and cognitive decline.


The report was reported at the Alzheimer's Association International Conference® 2014 in Copenhagen


Loss of smell sense linked to amyloid-beta protein

An animal study has shown that olfactory dysfunction occurs much earlier than cognitive dysfunction, and that this is related to the amyloid-beta protein. Although it’s been thought that this protein is expressed only in the central nervous system, the study detected direct expression of the protein in the olfactory epithelium, part of the peripheral nervous system. Moreover, the amyloid-beta protein had a fatal effect on olfactory nerve cells in the olfactory epithelium and directly induced the failure of olfactory function.

A less alarming explanation for why our sense of smell tends to decline in old age comes from a mouse study that found that fewer stem cells become olfactory cells in old age as they tend to remain in the stem cell pool and become less active.



Poor sense of smell linked to greater mortality risk

Following on from a previous study in which more than 2,200 older adults (71-82) undertook smell identification tests, investigation 13 years later found that a poor sense of smell was linked to a 46% greater risk of dying within 10 years compared with those ranked as having a good sense of smell. Poor sense of smell was particularly linked to death from dementia and Parkinson’s disease, with some signs that poor smell might also be linked to death from cardiovascular disease. There was no link between poor sense of smell and death from cancer or respiratory diseases. 22% of the overall increased risk of death among those with a poorer sense of smell was down to neurodegenerative diseases.

The link was only present among those who were in very good health at the start of the study.





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Reduced face memorization ability in those with MCI








Full text available at https://www.nature.com/articles/s41598-017-14585-5




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Personality changes during transition to MCI










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Smell tests provide early evidence of dementia

  • Several tests have been developed to assess this.


Smell test improves accuracy of MCI & Alzheimer's diagnosis





A new smell test


The new test is actually four tests:





Validation of UPSIT











[4209] Quarmley, M., Moberg P. J., Mechanic-Hamilton D., Kabadi S., Arnold S. E., Wolk D. A., et al.
(2017).  Odor Identification Screening Improves Diagnostic Classification in Incipient Alzheimer’s Disease.
Journal of Alzheimer's Disease. 55(4), 1497 - 1507.

[4210] Dhilla, A. Alefiya, Asafu-Adjei J., Delaney M. K., Kelly K. E., Gomez-Isla T., Blacker D., et al.
Annals of Neurology. 80(6), 846 - 857.




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Long-winded speech could be early sign of Alzheimer's



  • were much less concise in conveying information
  • produced much longer sentences
  • had a hard time staying on point
  • were much more roundabout in getting their point across.









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