The study found that each of the risk factors led to a decrease in cognitive performance of up to three years.

A new study finds that dementia risk might be more determined by lifestyle rather than age.

According to recent Baycrest research, adults without dementia risk factors like smoking, diabetes, or hearing loss had brain health comparable to that of those who are 10 to 20 years younger than them. According to the research, only one dementia risk factor can age a person’s cognition by up to three years.

“Our results suggest lifestyle factors may be more important than age in determining someone’s level of cognitive functioning. This is great news since there’s a lot you can do to modify these factors, such as managing diabetes, addressing hearing loss, and getting the support you need to quit smoking,” says Dr. Annalise LaPlume, Postdoctoral Fellow at Baycrest’s Rotman Research Institute (RRI) and the study’s lead author.


The research is one of the first to look at lifestyle risk factors for dementia across the entire lifespan.

“While most studies of this nature look at mid- and older-adulthood, we also included data from participants as young as 18, and we found that risk factors had a negative impact on cognitive performance across all ages. This is crucial as it means risk factors can and should be addressed as early as possible,” says Dr. Nicole Anderson, Senior Scientist at the RRI, Associate Scientific Director of Baycrest’s Kimel Family Centre for Brain Health and Wellness, and senior author of this study.

The study, recently published in the journal Alzheimer’s & Dementia: Diagnosis, Assessment, and Disease Monitoring, a journal of the Alzheimer’s Association, included data from 22,117 people aged 18 to 89 who completed the Cogniciti Brain Health Assessment, developed by Baycrest. Participants took the test in their own homes by going to the Cogniciti website. The test takes around 20 minutes to complete and consists of a background questionnaire and four cognitive tasks.


The researchers examined how eight modifiable risk factors for dementia—low education (less than a high school diploma), hearing loss, traumatic brain injury, alcohol or substance abuse, hypertension, smoking (currently or in the past four years), diabetes, and depression—affected participants’ performance on memory and attention tests.

Each factor caused a reduction in cognitive function that was equivalent to three years of age, with each additional factor having a similar effect. For instance, having three risk factors could result in a decline in cognitive function that is comparable to nine years of aging. As individuals aged, the consequences of the risk variables and their prevalence also rose.

“All in all, our research shows that you have the power to decrease your risk of cognitive decline and dementia,” says Dr. LaPlume. “Start addressing any risk factors you have now, whether you’re 18 or 90, and you’ll support your brain health to help yourself age fearlessly.”

Reference: “The adverse effect of modifiable dementia risk factors on cognition amplifies across the adult lifespan” by Annalise A. LaPlume, Ph.D., Larissa McKetton, Ph.D., Brian Levine, Ph.D., Angela K. Troyer, Ph.D. and Nicole D. Anderson, Ph.D., 13 July 2022, Alzheimer’s & Dementia Diagnosis Assessment & Disease Monitoring.
DOI: 10.1002/dad2.12337


This study was funded by the Alzheimer Society of Canada, and the Natural Sciences and Engineering Research Council of Canada.

With additional funding, the researchers could look further into the differences between normal agers and “super agers” – people who have the identical cognitive performance to those several decades younger than them.

The structure of many important molecules involved in anaphylaxis to mammalian meat has been uncovered, opening the door to potential future treatments.

The genetic and molecular structure of certain key molecules connected to the potentially fatal mammalian-meat allergy caused by tick bites has been revealed by scientists.


Researchers from the Garvan Institute of Medical Research led the study, which describes how antibodies interact with the sugar molecule galactose-α-1,3-galactose (alpha-gal/α-gal), which is produced by all mammals with the exception of humans and higher primates. It further supports the notion that α-gal serves as the key molecule for this particular allergy.

When some tick species, such as the Eastern Australian-endemic paralysis tick Ixodes holocyclus, bite people and expose them to α-gal, the immune system may identify the exposure as dangerous and trigger an allergic reaction, sometimes with life-threatening effects.

Professor Daniel Christ (right) looks at the structure of an antibody molecule. Credit: Garvan Institute of Medical Research

The molecular research, according to the study’s lead author Professor Daniel Christ, Head of Antibody Therapeutics and Director of the Centre for Targeted Therapy at Garvan, revealed that a certain antibody type (3-7) has a natural pocket into which α-gal fits well.

“We have more than 70 types of antibodies and this one is significantly overrepresented with α-gal recognition. We seem to be genetically predisposed to being sensitive to this sugar,” Professor Christ says.

The new study, recently published in the journal Proceedings of the National Academy of Sciences, paves the way for potential therapeutic candidates for treating the rare allergic response.

The evolutionary benefit to an immune reaction to α-gal

Scientists analyzed the blood of patients with mammalian-meat allergy to determine which antibodies were produced: the 3-7 type was found frequently in response to α-gal.


The data points to an evolutionary benefit of having an antibody response that can mobilize against α-gal.

“Humans lost the capacity to produce α-gal throughout evolution, but we don’t know why,” says Associate Professor Joanne Reed, co-senior author of this study, from the Westmead Institute. “The suspicion is that it has to do with protection against infectious disease.”

Professor Christ points to recent research on malaria, which shows the Plasmodium parasite has an α-gal coating on its surface. Rapid immune response to α-gal could destroy the parasite before it takes hold, protecting a person from malaria.

NSW is a global hotspot for tick-induced mammalian-meat allergy

Sydney’s northern region is a global hot spot for mammalian-meat allergy, with more than 1800 cases reported and the highest prevalence in the world. The Sunshine Coast hinterland around Maleny in Queensland is also another hot spot. The paralysis tick (Ixodes holocyclus) is found in those areas.

Professor Sheryl van Nunen, an allergy specialist at Sydney’s Northern Beaches Hospital, and a co-author of the paper, was the first clinician to link tick bites with mammalian-meat allergy. “There isn’t a week go by that I wouldn’t see two people with this allergy,” she says.

Why some people develop anaphylaxis and others never respond is unknown. Professor van Nunen says it could be related to the number of tick bites, how much saliva is injected, or genetic sensitivity.

Exposure happens when α-gal, present in the saliva of certain tick species, is injected during a bite, says Professor van Nunen. About one-third of people who have developed a sensitivity to α-gal will exhibit symptoms of an allergy to mammalian meat, she says. And another bite can more than double the allergic response. Some people with a severe allergy can be affected by the presence of meat products in food, like beef broth, soft cheeses such as feta or goat’s cheese, or even gelatin.

Collaboration is the path to science excellence

Professor Robert Brink, Translation Research Pillar Director at Garvan, highlights the excellence and interdisciplinary nature of the work. “The Garvan Institute of Medical Research has world-leading capabilities in both antibody science and genomics. This study combines these two fields to advance our understanding of mammalian-meat allergy, an important and growing health issue for Australia, and for NSW in particular.”

Reference: “Genetic and structural basis of the human anti-α-galactosyl antibody response” by David B. Langley, Peter Schofield, Damien Nevoltris, Jennifer Jackson, Katherine J. L. Jackson, Tim J. Peters, Melanie Burk, Jacqueline M. Matthews, Antony Basten, Christopher C. Goodnow, Sheryl van Nunen, Joanne H. Reed and Daniel Christ, 8 July 2022, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2123212119

A new type of macular dystrophy, which is a cause of central vision loss, has been discovered through genetic and clinical research.

A new disease that damages the macula, a small region of the light-sensing retina required for sharp, central vision, has been discovered by National Eye Institute (NEI) researchers. The researchers have published their findings on the unnamed new macular dystrophy in the journal JAMA Ophthalmology. NEI is a branch of the National Institutes of Health.

Macular dystrophies are disorders that often result in central vision loss due to abnormalities in various genes, including ABCA4, BEST1, PRPH2, and TIMP3.


For instance, individuals with Sorsby Fundus Dystrophy, a hereditary eye disorder that is specifically linked with TIMP3 variations, often develop symptoms in adulthood. Due to choroidal neovascularization, which is the growth of new, irregular blood vessels behind the retina that leak fluid and disrupt vision, they often experience abrupt changes in visual acuity.

TIMP3 is a protein that helps regulate retinal blood flow and is secreted from the retinal pigment epithelium (RPE), a layer of tissue that nourishes and supports the retina’s light-sensing photoreceptors. All TIMP3 gene mutations reported are in the mature protein after it has been “cut” from RPE cells in a process called cleavage.

“We found it surprising that two patients had TIMP3 variants not in the mature protein, but in the short signal sequence the gene uses to ‘cut’ the protein from the cells. We showed these variants prevent cleavage, causing the protein to be stuck in the cell, likely leading to retinal pigment epithelium toxicity,” said Bin Guan, Ph.D., lead author.


The research team followed these findings with clinical evaluations and genetic testing of family members to verify that the two new TIMP3 variants are connected to this atypical maculopathy.

“Affected individuals had scotomas, or blind spots, and changes in their maculas indicative of disease, but, for now, they have preserved central vision and no choroidal neovascularization, unlike typical Sorsby Fundus Dystrophy”, said Cathy Cukras, M.D., Ph.D., a Lasker tenure-track investigator and medical retina specialist who clinically evaluated the patients.

NEI’s Ophthalmic Genomics Laboratory gathers and manages specimens and diagnostic data from patients who have been recruited into multiple studies within the NEI clinical program to facilitate research of rare eye diseases, including Sorsby Fundus Dystrophy.

“Discovering novel disease mechanisms, even in known genes like TIMP3, may help patients that have been looking for the correct diagnosis, and will hopefully lead to new therapies for them,” said Rob Hufnagel, M.D., Ph.D., senior author, and director of the Ophthalmic Genomics Laboratory at NEI.


Reference: “Early-Onset TIMP3-Related Retinopathy Associated With Impaired Signal Peptide” by Bin Guan, Ph.D., Laryssa A. Huryn, MD, Andrew B. Hughes, BS, Zhiyu Li, MD, Chelsea Bender, BS, Delphine Blain, MS, MBA, Amy Turriff, MS, Catherine A. Cukras, MD, Ph.D. and Robert B. Hufnagel, MD, Ph.D., 9 June 2022, JAMA Ophthalmology.
DOI: 10.1001/jamaophthalmol.2022.1822

The study was funded by the NEI Intramural Research Program.

Recalling memories requires the cooperation of several brain regions.

When you have a memorable evening at a restaurant, more than just the food stays in your memory. A vivid memory of the evening is created by the smells, the décor, the music played by the band, the conversations, and several other elements. Later, bringing back just one of these impressions could be enough to relive the entire experience.

According to recent research, complex memories in the brain are made up of a whole and its parts. The hippocampus, a part of the brain long thought to be the seat of memory, is where the general experience is kept, but the specific details are parsed and stored in a different part of the brain, the prefrontal cortex. In the future, this separation makes sure that exposure to any one cue will be enough to activate the prefrontal cortex, which will then access the hippocampus to remember the whole memory.


The research, which was published in Nature, sheds light on how the brain processes memories in different ways and offers new insight into how memories are recalled, which is a process that is less understood than memory storage.

It has been challenging to study memory as a distributed brain process, in part due to technical limitations. Priya Rajasethupathy, a neuroscientist at Rockefeller University and her colleagues developed novel techniques to simultaneously record and manipulate neural activity from multiple brain areas as mice navigated multisensory experiences, encountering various sights, sounds, and smells while in an endless corridor in virtual reality.

The researchers trained the mice to associate different rooms, which were composed of different combinations of the sensory cues, as rewarding or aversive experiences. Later on, nudged by a specific scent or sound, the mice were able to recall the broader experience and knew whether to happily expect sugar water or look out for an annoying puff of air.


The experiments demonstrated that while the entorhinal-hippocampal pathway, a well-studied circuit involving the hippocampus and its surrounding region, was essential for forming and storing the experiences, the individual sensory features were being shipped off to prefrontal neurons. Later, when mice encountered particular sensory features, a different circuit was engaged. This time, the prefrontal neurons communicated with the hippocampus to conjure the relevant global memory.

“This suggests that there’s a dedicated pathway for memory recall, separate from memory formation,” says Nakul Yadav, the study’s first author and a graduate student co-mentored by Rajasethupathy and by Conor Liston, a neuroscientist at Weill Cornell Medicine.

These findings have implications for the treatment of conditions such as Alzheimer’s disease, where the deficits are thought to be more related to memory recall than storage. The existence of separate storage and retrieval pathways in the brain suggests that targeting prefrontal recall pathways may be more therapeutically promising, Rajasethupathy says.

Reference: “Prefrontal feature representations drive memory recall” by Nakul Yadav, Chelsea Noble, James E. Niemeyer, Andrea Terceros, Jonathan Victor, Conor Liston, and Priyamvada Rajasethupathy, 13 July 2022, Nature.
DOI: 10.1038/s41586-022-04936-2