Memory Research News in Alzheimer's & Dementia

Rapid blood pressure drops in middle age linked to dementia in old age

  • A large study indicates that an inclination to dizziness on standing up is associated with a greater risk of developing cognitive impairment and dementia decades later.

Data from over 11,500 participants in the Atherosclerosis Risk in Communities (ARIC) cohort has found evidence that orthostatic hypotension in middle age may increase the risk of cognitive impairment and dementia 20 years later.

Orthostatic hypotension is the name for the experience of dizziness or light-headedness on standing up. Previous research has suggested an association between orthostatic hypotension and cognitive decline in older adults.

In this study, participants aged 45-64 were tested for orthostatic hypotension in 1987. Those with it (703, around 6%) were 40% more likely to develop dementia in the next 20 years. They also had some 15% more cognitive decline.

Orthostatic hypotension was defined as a drop of 20 mmHg or more in systolic blood pressure or 10 mmHg or more in diastolic blood pressure, when the individual stood up after 20 minutes lying down.

More work is needed to understand the reason for the association.

https://www.eurekalert.org/pub_releases/2017-03/jhub-rbp030817.php

Rawlings, Andreea. 2017. Orthostatic Hypotension is Associated with 20-year Cognitive Decline and Incident Dementia: The Atherosclerosis Risk in Communities (ARIC) Study. Presented March 10 at the American Heart Association's EPI|LIFESTYLE 2017 Scientific Sessions in Portland, Oregon.

Brain proteins involved in the development of Alzheimer's

  • When a particular fat molecule in the brain doesn't break down properly, cognition gets harder, and there's an increase in amyloid precursor proteins (which are part of the Alzheimer's cascade).
  • Tau proteins are also involved in the Alzheimer's cascade. A new study shows that individuals vary markedly in how quickly they spread in the brain.
  • A protein called SIRT6 has now been found to be crucially involved in DNA repair, to be severely deficient in those with Alzheimer's, and to be associated with learning impairment in mice.
  • A protein called NPTX2 may explain why some brains can cope with high levels of amyloid-beta much better than others.
Disrupted fat breakdown in the brain involved in Alzheimer’s?

The brain is rich in lipids (fats), which not only help insulate nerve fibers, but are also a crucial part of the membranes surrounding brain cells. One particular type that is highly enriched in the brain (sphingolipids) produces something called S1P. A mouse study has now found that when their brains were blocked from breaking down S1P, the mice began to show learning and memory problems. Moreover, there was a significant increase in the amount of APP (the precursor of amyloid-beta proteins, characteristic of Alzheimer’s) in their brains.

The problem is that S1P is broken down into simpler products, one of which is vital for autophagy — how cells digest and recycle their own components, when they don’t work properly. This finding suggests a new mechanism for the development of Alzheimer's and other dementias.

https://www.eurekalert.org/pub_releases/2017-05/uob-dfb051917.php

Spread of tau protein measured in Alzheimer's brains

A study involving 16 patients at different stages of Alzheimer's disease, who underwent memory tests and PET scans at 17-month intervals, has found a marked difference between individuals in how much tau protein is in the brain and how quickly it spreads. Moreover, there was a strong correlation between the amount of tau and how much episodic memory was impaired.

This may help explain why Alzheimer's progresses at such different rates between people.

https://www.eurekalert.org/pub_releases/2017-05/ki-sot051617.php

Low levels of protein SIRT6 implicated in Alzheimer's

It’s generally thought that aging is the result of DNA damage accumulation, because of the breakdown in DNA repair processes. A new mouse study has found that a crucial element in DNA repair is a protein called SIRT6. Mice deficient in SIRT6 showed marked learning impairments, and their brains showed more DNA damage, cell death, and hyperphosphorylated tau (a critical mark in several neurodegenerative diseases, as well as Alzheimer's).

Humans with Alzheimer's disease were also found to have a severe deficiency of the SIRT6 protein.

It’s suggested that SIRT6 loss, leading to DNA damage accumulation, may be the beginning of the chain that ends in Alzheimer’s and other neurodegenerative disease.

https://www.eurekalert.org/pub_releases/2017-05/aabu-bur050517.php

Low levels of 'memory protein' linked to cognitive decline in Alzheimer's disease

We know that high levels of amyloid-beta plaques are characteristic of Alzheimer's, but we also know that people can have high levels of amyloid without displaying symptoms of Alzheimer's. A new study shows that the reason for this apparent discrepancy may lie with another protein, called NPTX2.

It appears that memory loss occurs when high amyloid-beta occurs in combination with low levels of NPTX2.

The gene which expresses the protein NPTX2 belongs to a set of genes known as "immediate early genes," which are activated almost instantly in brain cells when an experience results in a new memory. The protein is used by neurons to strengthen the circuits that encode memories.

A study of 144 archived human brain tissue samples revealed that NPTX2 protein levels were reduced by as much as 90% in brain samples from people with Alzheimer's compared with age-matched brain samples without Alzheimer's. People with amyloid plaques who had never shown signs of Alzheimer's, on the other hand, had normal levels of NPTX2.

A mouse study then confirmed this link, by showing that cell function wasn’t affected by a lack of NPTX2 until a gene that increases amyloid generation was added. With both amyloid and no NPTX2, fast-spiking interneurons could not control brain "rhythms" which synchronize activity between neurons, thus creating circuits / networks that encode memories. Additionally, a glutamate receptor essential for interneuron function was also reduced — as it was in the human Alzheimer's brains.

A study of NPTX2 protein levels in the cerebrospinal fluid (CSF) of 60 living Alzheimer's patients and 72 controls found that

  • NPTX2 levels were 36-70% lower in people with Alzheimer's
  • lower cognitive scores were associated with lower levels of NPTX2
  • NPTX2 levels were more closely correlated with cognitive performance that tau proteins and amyloid-beta
  • NPTX2 correlated with the size of the hippocampus

https://www.eurekalert.org/pub_releases/2017-04/jhm-llo042417.php

Reference: 

[4267] Mitroi DN, Karunakaran I, Gräler M, Saba JD, Ehninger D, Ledesma MDolores, van Echten-Deckert G. SGPL1 (sphingosine phosphate lyase 1) modulates neuronal autophagy via phosphatidylethanolamine production. Autophagy [Internet]. 2017 ;13(5):885 - 899. Available from: http://dx.doi.org/10.1080/15548627.2017.1291471

[4268] Chiotis K, Saint-Aubert L, Rodriguez-Vieitez E, Leuzy A, Almkvist O, Savitcheva I, Jonasson M, Lubberink M, Wall A, Antoni G, et al. Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia. Molecular Psychiatry [Internet]. 2017 . Available from: https://www.nature.com/mp/journal/vaop/ncurrent/full/mp2017108a.html

[4269] Kaluski S, Portillo M, Besnard A, Stein D, Einav M, Zhong L, Ueberham U, Arendt T, Mostoslavsky R, Sahay A, et al. Neuroprotective Functions for the Histone Deacetylase SIRT6. Cell Reports [Internet]. 2017 ;18(13):3052 - 3062. Available from: http://www.cell.com/cell-reports/abstract/S2211-1247(17)30325-X

[4270] Xiao M-F, Xu D, Craig MT, Pelkey KA, Chien C-C, Shi Y, Zhang J, Resnick S, Pletnikova O, Salmon D, et al. NPTX2 and cognitive dysfunction in Alzheimer’s Disease. eLife [Internet]. 2017 ;6:e23798. Available from: https://elifesciences.org/articles/23798

Spatial impairment early sign of Alzheimer’s

  • A cognitive test has been shown to identify early shrinking of the brain region first affected by Alzheimer's.

A Canadian study involving 40 older adults (59-81), none of whom were aware of any major memory problems, has found that those scoring below 26 on the Montreal Cognitive Assessment (MoCA) dementia screening test also showed shrinking of the anterolateral entorhinal cortex. This brain region is the first affected in the development of Alzheimer's disease. The study found specifically that this area of the brain is involved in configural processing — that is, processing the spatial arrangement of an object's elements. Accordingly, this task provides a very early indicator of developing Alzheimer's.

You can do a preliminary assessment of your memory using Baycrest's scientifically-validated, online brain health assessment tool, Cogniciti at http://www.cogniciti.com.

https://www.eurekalert.org/pub_releases/2017-05/bcfg-dbc051117.php

Reference: 

[4265] Olsen RK, Yeung L-K, Noly-Gandon A, D’Angelo MC, Kacollja A, Smith VM, Ryan JD, Barense MD. Human anterolateral entorhinal cortex volumes are associated with cognitive decline in aging prior to clinical diagnosis. Neurobiology of Aging [Internet]. Submitted . Available from: http://www.sciencedirect.com/science/article/pii/S0197458017301537

Aerobic exercise preserves brain volume and improves cognition in those with MCI

  • Regular exercise has been found to reduce brain shrinkage in those with mild cognitive impairment.

A study involving 35 adults with MCI found that those who exercised four times a week over a six-month period increased their volume of gray matter. But those who participated in aerobic exercise experienced significantly greater gains than those who just stretched, who also showed signs of white matter loss.

Aerobic activity included treadmill, stationary bike or elliptical training.

The study was presented at the annual meeting of the Radiological Society of North America (RSNA) in November, 2016.

https://www.eurekalert.org/pub_releases/2016-11/rson-aep111716.php

One in 4 elderly Australian women have dementia

  • A new estimation technique has raised the dementia rates for Australian women from 20% to 26%.

In Australia, it has beens estimated that 9% of people aged over 65, and 30% of those aged over 85 have dementia. However, these estimates are largely based on older data from other countries, or small local samples.

A new technique based on an ecological method for estimating species population size has been used to estimate dementia rates in the Australian population. The study used 16 years of data from 12,432 Australian women born between 1921 and 1926 who participated in the Women's Health Australia study. Survey data was linked to aged care assessments, the National Death Index, the Pharmaceutical Benefits Scheme, and hospital admissions data to find any instance where the women participating in the study were diagnosed with dementia. This additional data helped overcome the problem of such studies, where participants often just drop out, and the cause isn’t known.

Applying the ecological technique to all this data led to the conclusion that an additional 728 women with dementia had not been identified, increasing the 16 year prevalence from 20.4 to 26.0%. Breaking this down by age, we have:

  • 70-74: 0.3%
  • 75-79: 3.7%
  • 80-84: 16.6%
  • 85+: 31%

https://www.eurekalert.org/pub_releases/2017-03/uoq-oif031617.php

Reference: 

[4266] Waller M, Mishra GD, Dobson AJ. Estimating the prevalence of dementia using multiple linked administrative health records and capture–recapture methodology. Emerging Themes in Epidemiology [Internet]. 2017 ;14:3. Available from: http://dx.doi.org/10.1186/s12982-017-0057-3