1. Some patients with dementia may experience delayed-onset PTSD

    July 27, 2017 by Ashley

    From the Wiley press release:

    Delayed-onset post-traumatic symptoms in the elderly may be misdiagnosed as falling under the umbrella of behavioural and psychological symptoms of dementia (BPSD), according to a recent review.

    The review describes three cases where post-traumatic stress disorder (PTSD) symptoms are experienced by patients suffering with dementia long after the original traumatic event.

    Considering PTSD in individuals with dementia is important because PTSD is usually associated with working-age adults and is infrequently diagnosed in the elderly. In the early stages of dementia, recognising early life trauma may enable patients to access psychological therapy prior to significant cognitive decline. In patients with more advanced dementias, an awareness of earlier trauma exposure can help clinicians differentiate between delayed PTSD and BPSD in patients suffering with emotional and behavioural disturbances.

    “Every patient with dementia has a unique narrative, which if captured in the earlier stages of the disease, enables clinicians and their families to understand the origin of their distress. Therefore, it is important to look for a history of previous trauma in patients with BPSD as this could be due to delayed onset PTSD,” said Dr. Tarun Kuruvilla, senior author of the Progress in Neurology & Psychiatry review.


  2. Traumatic brain injury associated with dementia in working-age adults

    July 26, 2017 by Ashley

    From the University of Helsinki press release:

    According to a study encompassing the entire Finnish population, traumatic brain injury associated with an increased risk for dementia in working-age adults. Yet, no such relationship was found between traumatic brain injury and later onset of Parkinson’s disease or ALS.

    The researchers believe that these results may play a significant role for the rehabilitation and long-term monitoring of traumatic brain injury patients.

    Traumatic brain injuries (TBI) are among the top causes of death and disability, particularly among the young and middle aged. Approximately one in three that suffer from moderate-to-severe TBI die, and approximately half of the survivors will suffer from life-long disabilities.

    Degenerative brain diseases include memory disorders such as Alzheimer’s disease as well as Parkinson’s disease and amyotrophic lateral sclerosis (ALS). While the connection between TBI and degenerative brain diseases has been known, no comprehensive research data exist on the impact of TBI on degenerative brain diseases among adults of working age.

    Researchers from the University of Helsinki and the Helsinki University Hospital have now examined the relationship between TBI and degenerative brain diseases in a study encompassing the entire Finnish population. The study combined several nationwide registers to monitor more than 40,000 working-age adults, who survived the initial TBI, for ten years. Importantly, the persons´ level of education and socioeconomic status were accounted for.

    “It seems that the risk for developing dementia after TBI is the highest among middle-aged men. The more severe the TBI, the higher the risk for subsequent dementia. While previous studies have identified good education and high socioeconomic status as protective factors against dementia, we did not discover a similar effect among TBI survivors,” explains Rahul Raj, docent of experimental neurosurgery and one of the primary authors of the study.

    A significant discovery is that the risk of dementia among TBI survivors who have seemingly recovered well remains high for years after the injury. Raj points out that TBI patients may occasionally be incorrectly diagnosed with dementia due to the damage caused by the TBI itself, but such possible errors were considered in the study.

    “According to our results, it might be so that the TBI triggers a process that later leads to dementia.”

    “These results are significant for the rehabilitation and monitoring of TBI patients. Such a reliable study of the long-term impact of TBI has previously been impossible,” says Professor Jaakko Kaprio, a member of the research group.

    The WHO has predicted that TBI will become a leading cause of death and long-term illness during the next ten years. Already one per cent of the population in the United States suffers from a long-term disability caused by TBI. In western countries, the ageing of the population and age-related accidents increase the amount of TBIs, while in Asia, TBIs caused by traffic accidents are on the rise.

    Dementia is commonly seen as a problem of the elderly. However, the Finnish study shows that TBI may cause dementia to develop before old age, and that dementia caused by injuries are much more common than was thought.

    “It is a tragedy when an adult of working age develops dementia after recovering from a brain injury, not just for the patient and their families, but it also negatively impacts the whole society. In the future, it will be increasingly important to prevent TBIs and to develop rehabilitation and long-term monitoring for TBI patients,” says Docent Raj.


  3. Sleep problems may be early sign of Alzheimer’s

    July 24, 2017 by Ashley

    From the American Academy of Neurology press release:

    Poor sleep may be a sign that people who are otherwise healthy may be more at risk of developing Alzheimer’s disease later in life than people who do not have sleep problems, according to a study published in the July 5, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. Researchers have found a link between sleep disturbances and biological markers for Alzheimer’s disease found in the spinal fluid.

    “Previous evidence has shown that sleep may influence the development or progression of Alzheimer’s disease in various ways,” said study author Barbara B. Bendlin, PhD, of the University of Wisconsin-Madison. “For example, disrupted sleep or lack of sleep may lead to amyloid plaque buildup because the brain’s clearance system kicks into action during sleep. Our study looked not only for amyloid but for other biological markers in the spinal fluid as well.”

    Amyloid is a protein that can fold and form into plaques. Tau is a protein that forms into tangles. These plaques and tangles are found in the brains of people with Alzheimer’s disease.

    For the study, researchers recruited 101 people with an average age of 63 who had normal thinking and memory skills but who were considered at risk of developing Alzheimer’s, either having a parent with the disease or being a carrier of a gene that increases the risk for Alzheimer’s disease called apolipoprotein E or APOE. Participants were surveyed about sleep quality. They also provided spinal fluid samples that were tested for biological markers of Alzheimer’s disease.

    Researchers found that people who reported worse sleep quality, more sleep problems and daytime sleepiness had more biological markers for Alzheimer’s disease in their spinal fluid than people who did not have sleep problems. Those biological markers included signs of amyloid, tau and brain cell damage and inflammation.

    “It’s important to identify modifiable risk factors for Alzheimer’s given that estimates suggest that delaying the onset of Alzheimer’s disease in people by a mere five years could reduce the number of cases we see in the next 30 years by 5.7 million and save $367 billion in health care spending,” said Bendlin.

    While some of these relationships were strong when looking at everyone as a group, not everyone with sleep problems has abnormalities in their spinal fluid. For example, there was no link between biological markers in the spinal fluid and obstructive sleep apnea.

    The results remained the same when researchers adjusted for other factors such as use of medications for sleep problems, amount of education, depression symptoms or body mass index.

    “It’s still unclear if sleep may affect the development of the disease or if the disease affects the quality of sleep,” said Bendlin. “More research is needed to further define the relationship between sleep and these biomarkers.”

    Bendlin added, “There are already many effective ways to improve sleep. It may be possible that early intervention for people at risk of Alzheimer’s disease may prevent or delay the onset of the disease.”

    One limitation of the study was that sleep problems were self-reported. Monitoring of sleep patterns by health professionals may be beneficial in future studies.


  4. No link seen between traumatic brain injury and cognitive decline

    by Ashley

    From the Boston University Medical Center press release:

    Although much research has examined traumatic brain injury (TBI) as a possible risk factor for later life dementia from neurodegenerative diseases such as Alzheimer’s disease (AD), little is known regarding how TBI influences the rate of age-related cognitive change. A new study now shows that history of TBI (with loss of consciousness) does not appear to affect the rate of cognitive change over time for participants with normal cognition or even those with AD dementia.

    These findings appear in the Journal of Alzheimer’s Disease.

    More than 10 million individuals worldwide are affected annually by TBI, however the true prevalence is likely even greater given that a majority of TBIs are mild in severity and may not be recognized or reported. TBI is a major public health and socioeconomic concern resulting in $11.5 billion in direct medical costs and $64.8 billion in indirect costs to the U.S. health system in 2010 alone.

    According to the researchers the relationship between TBI and long-term cognitive trajectories remains poorly understood due to limitations of previous studies, including small sample sizes, short follow-up periods, biased samples, high attrition rates, limited or no reports of exposure to repetitive head impacts (such as those received through contact sports), and very brief cognitive test batteries.

    In an effort to examine this possible connection, researchers compared performance on cognitive tests over time for 706 participants (432 with normal cognition; 274 AD dementia) from the National Alzheimer’s Coordinating Center database. Normal and AD dementia participants with a history of TBI with loss of consciousness were matched to an equal number of demographically and clinically similar participants without a TBI history. The researchers also examined the possible role of genetics in the relationship between TBI and cognitive decline by studying a gene known to increase risk for AD dementia, the APOE ?4 gene.

    “Although we expected the rates of cognitive change to differ significantly between those with a history of TBI compared to those with no history of TBI, we found no significant difference between the groups, regardless of their APOE genotype,” explained corresponding author Robert Stern, PhD, Director of the Clinical Core of the Boston University Alzheimer’s Disease Center (BU ADC) and professor of neurology, neurosurgery and anatomy and neurobiology at Boston University School of Medicine.

    The study’s first author Yorghos Tripodis, PhD, Associate Director of the Data Management and Biostatistics Core of the BU ADC and associate professor of Biostatistics at Boston University School of Public Health, cautioned, “Our findings should still be interpreted cautiously due to the crude and limited assessment of TBI history available through the NACC database.” The researchers recommended that future studies should collect information on the number of past TBIs (including mild TBIs, as well as exposure to sub-concussive trauma through contact sports and other activities) along with time since TBI, which may play a significant role in cognitive change.


  5. Study examines link between sleep disruptions and Alzheimer’s

    July 23, 2017 by Ashley

    From the Washington University in St. Louis press release:

    A good night’s sleep refreshes body and mind, but a poor night’s sleep can do just the opposite. A study from Washington University School of Medicine in St. Louis, Radboud University Medical Centre in the Netherlands, and Stanford University has shown that disrupting just one night of sleep in healthy, middle-aged adults causes an increase in amyloid beta, a brain protein associated with Alzheimer’s disease. And a week of tossing and turning leads to an increase in another brain protein, tau, which has been linked to brain damage in Alzheimer’s and other neurological diseases.

    “We showed that poor sleep is associated with higher levels of two Alzheimer’s-associated proteins,” said David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor, head of the Department of Neurology and the study’s senior author. “We think that perhaps chronic poor sleep during middle age may increase the risk of Alzheimer’s later in life.”

    These findings, published July 10 in the journal Brain, may help explain why poor sleep has been associated with the development of dementias such as Alzheimer’s.

    More than 5 million Americans are living with Alzheimer’s disease, which is characterized by gradual memory loss and cognitive decline. The brains of people with Alzheimer’s are dotted with plaques of amyloid beta protein and tangles of tau protein, which together cause brain tissue to atrophy and die. There are no therapies that have been proven to prevent, slow or reverse the course of the disease.

    Previous studies by Holtzman, co-first author Yo-El Ju, MD, an assistant professor of neurology, and others have shown that poor sleep increases the risk of cognitive problems. People with sleep apnea, for example, a condition in which people repeatedly stop breathing at night, are at risk for developing mild cognitive impairment an average of 10 years earlier than people without the sleep disorder. Mild cognitive impairment is an early warning sign for Alzheimer’s disease.

    But it wasn’t clear how poor sleep damages the brain. To find out, the researchers — Holtzman; Ju; co-first author and graduate student Sharon Ooms of Radboud; Jurgen Claassen, MD, PhD, of Radboud; Emmanuel Mignot, MD, PhD, of Stanford; and colleagues — studied 17 healthy adults ages 35 to 65 with no sleep problems or cognitive impairments. Each participant wore an activity monitor on the wrist for up to two weeks that measured how much time they spent sleeping each night.

    After five or more successive nights of wearing the monitor, each participant came to the School of Medicine to spend a night in a specially designed sleep room. The room is dark, soundproof, climate-controlled and just big enough for one; a perfect place for sleeping, even as the participants wore headphones over the ears and electrodes on the scalp to monitor brain waves.

    Half the participants were randomly assigned to have their sleep disrupted during the night they spent in the sleep room. Every time their brain signals settled into the slow-wave pattern characteristic of deep, dreamless sleep, the researchers sent a series of beeps through the headphones, gradually getting louder, until the participants’ slow-wave patterns dissipated and they entered shallower sleep.

    The next morning, the participants who had been beeped out of slow-wave sleep reported feeling tired and unrefreshed, even though they had slept just as long as usual and rarely recalled being awakened during the night. Each underwent a spinal tap so the researchers could measure the levels of amyloid beta and tau in the fluid surrounding the brain and spinal cord.

    A month or more later, the process was repeated, except that those who had their sleep disrupted the first time were allowed to sleep through the night undisturbed, and those who had slept uninterrupted the first time were disturbed by beeps when they began to enter slow-wave sleep.

    The researchers compared each participant’s amyloid beta and tau levels after the disrupted night to the levels after the uninterrupted night, and found a 10 percent increase in amyloid beta levels after a single night of interrupted sleep, but no corresponding increase in tau levels. However, participants whose activity monitors showed they had slept poorly at home for the week before the spinal tap showed a spike in levels of tau.

    “We were not surprised to find that tau levels didn’t budge after just one night of disrupted sleep while amyloid levels did, because amyloid levels normally change more quickly than tau levels,” Ju said. “But we could see, when the participants had several bad nights in a row at home, that their tau levels had risen.”

    Slow-wave sleep is the deep sleep that people need to wake up feeling rested. Sleep apnea disrupts slow-wave sleep, so people with the disorder often wake up feeling unrefreshed, even after a full eight hours of shut-eye.

    Slow-wave sleep is also the time when neurons rest and the brain clears away the molecular byproducts of mental activity that accumulate during the day, when the brain is busily thinking and working.

    Ju thinks it is unlikely that a single night or even a week of poor sleep, miserable though it may be, has much effect on overall risk of developing Alzheimer’s disease. Amyloid beta and tau levels probably go back down the next time the person has a good night’s sleep, she said.

    “The main concern is people who have chronic sleep problems,” Ju said. “I think that may lead to chronically elevated amyloid levels, which animal studies have shown lead to increased risk of amyloid plaques and Alzheimer’s.”

    Ju emphasized that her study was not designed to determine whether sleeping more or sleeping better reduce risk of Alzheimer’s but, she said, neither can hurt.

    “Many, many Americans are chronically sleep-deprived, and it negatively affects their health in many ways,” Ju said. “At this point, we can’t say whether improving sleep will reduce your risk of developing Alzheimer’s. All we can really say is that bad sleep increases levels of some proteins that are associated with Alzheimer’s disease. But a good night’s sleep is something you want to be striving for anyway.”


  6. Sleep problems may be early sign of Alzheimer’s

    July 22, 2017 by Ashley

    From the American Academy of Neurology press release:

    Poor sleep may be a sign that people who are otherwise healthy may be more at risk of developing Alzheimer’s disease later in life than people who do not have sleep problems, according to a study published in the July 5, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. Researchers have found a link between sleep disturbances and biological markers for Alzheimer’s disease found in the spinal fluid.

    “Previous evidence has shown that sleep may influence the development or progression of Alzheimer’s disease in various ways,” said study author Barbara B. Bendlin, PhD, of the University of Wisconsin-Madison. “For example, disrupted sleep or lack of sleep may lead to amyloid plaque buildup because the brain’s clearance system kicks into action during sleep. Our study looked not only for amyloid but for other biological markers in the spinal fluid as well.”

    Amyloid is a protein that can fold and form into plaques. Tau is a protein that forms into tangles. These plaques and tangles are found in the brains of people with Alzheimer’s disease.

    For the study, researchers recruited 101 people with an average age of 63 who had normal thinking and memory skills but who were considered at risk of developing Alzheimer’s, either having a parent with the disease or being a carrier of a gene that increases the risk for Alzheimer’s disease called apolipoprotein E or APOE. Participants were surveyed about sleep quality. They also provided spinal fluid samples that were tested for biological markers of Alzheimer’s disease.

    Researchers found that people who reported worse sleep quality, more sleep problems and daytime sleepiness had more biological markers for Alzheimer’s disease in their spinal fluid than people who did not have sleep problems. Those biological markers included signs of amyloid, tau and brain cell damage and inflammation.

    “It’s important to identify modifiable risk factors for Alzheimer’s given that estimates suggest that delaying the onset of Alzheimer’s disease in people by a mere five years could reduce the number of cases we see in the next 30 years by 5.7 million and save $367 billion in health care spending,” said Bendlin.

    While some of these relationships were strong when looking at everyone as a group, not everyone with sleep problems has abnormalities in their spinal fluid. For example, there was no link between biological markers in the spinal fluid and obstructive sleep apnea.

    The results remained the same when researchers adjusted for other factors such as use of medications for sleep problems, amount of education, depression symptoms or body mass index.

    “It’s still unclear if sleep may affect the development of the disease or if the disease affects the quality of sleep,” said Bendlin. “More research is needed to further define the relationship between sleep and these biomarkers.”

    Bendlin added, “There are already many effective ways to improve sleep. It may be possible that early intervention for people at risk of Alzheimer’s disease may prevent or delay the onset of the disease.”

    One limitation of the study was that sleep problems were self-reported. Monitoring of sleep patterns by health professionals may be beneficial in future studies.


  7. Some patients with dementia may experience delayed-onset PTSD

    July 21, 2017 by Ashley

    From the Wiley press release:

    Delayed-onset post-traumatic symptoms in the elderly may be misdiagnosed as falling under the umbrella of behavioural and psychological symptoms of dementia (BPSD), according to a recent review.

    The review describes three cases where post-traumatic stress disorder (PTSD) symptoms are experienced by patients suffering with dementia long after the original traumatic event.

    Considering PTSD in individuals with dementia is important because PTSD is usually associated with working-age adults and is infrequently diagnosed in the elderly. In the early stages of dementia, recognising early life trauma may enable patients to access psychological therapy prior to significant cognitive decline. In patients with more advanced dementias, an awareness of earlier trauma exposure can help clinicians differentiate between delayed PTSD and BPSD in patients suffering with emotional and behavioural disturbances.

    “Every patient with dementia has a unique narrative, which if captured in the earlier stages of the disease, enables clinicians and their families to understand the origin of their distress. Therefore, it is important to look for a history of previous trauma in patients with BPSD as this could be due to delayed onset PTSD,” said Dr. Tarun Kuruvilla, senior author of the Progress in Neurology & Psychiatry review.


  8. Study suggests Alzheimer’s disease patients with psychosis more likely to be misdiagnosed

    July 18, 2017 by Ashley

    From the St. Michael’s Hospital press release:

    People with Alzheimer’s disease who experience psychosis — including delusions and hallucinations — are five times more likely to be misdiagnosed with dementia with Lewy bodies compared to patients who do not, new research suggests.

    Alzheimer’s disease is a type of dementia characterized by protein deposits in the brain including twisted fibers found inside brain cells. Dementia with Lewy bodies is believed to be caused by the buildup of a different abnormal protein aggregate found in nerve cells in the brain. Effective treatments for these conditions are still under development, but will almost certainly be different, according to the authors.

    Researchers also found that Alzheimer’s disease was misdiagnosed in 24 per cent of all cases, with false positive and false negative rates both being 12 per cent. Previous research suggested that the rate of misdiagnosis in Alzheimer’s disease ranged from 12-23 per cent.

    The findings, published online in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, raise concern that there may be an under appreciation of how common psychotic symptoms are in Alzheimer’s disease, said Dr. Corinne Fischer, director of the Memory Disorders Clinic at St. Michael’s Hospital in Toronto and lead author of the study.

    “Psychosis can be a symptom of Alzheimer’s disease, but it is a defining clinical feature in other types of dementia, including Parkinson’s disease related dementia and dementia with Lewy bodies,” she said. “Consequently, clinicians are more reluctant to diagnose a patient with Alzheimer’s disease when they present with delusions or hallucinations.”

    About 36 per cent of people with Alzheimer’s are thought to have delusions and 18 per cent have hallucinations. Psychotic symptoms are significant in Alzheimer’s patients because they have been shown to be associated with increased burden on caregivers, increased functional decline and more rapid progression of the disease.

    Researchers examined 961 people using data from the National Alzheimer’s Coordinating Centre database, collected from 29 Alzheimer’s disease centres in the United States between 2005 and 2012. They included participants who had been clinically diagnosed with Alzheimer’s while they were alive, as well as those whose autopsies showed they the signature physical signs of Alzheimer’s in their brains.

    Patients who experienced psychosis had a higher rate of false negative diagnosis and a lower rate of false positive diagnosis of Alzheimer’s disease compared to those who did not. Whether patients experienced delusions, hallucinations, or a combination of both did not affect the rate of misdiagnosis, according to the authors.

    The Alzheimer’s Society of Canada estimates there are 564,000 people living with dementia in Canada, and that number is expected to almost double over the next 15 years, thus reinforcing the relevance of the study’s findings according to Winnie Qian, a Master’s student in the Neuroscience Research Program at St. Michael’s and an author on the study.

    “An advantage of our study is that we used the final clinical diagnosis after years of follow-up, so the rate of misdiagnosis we described is the rate under ideal conditions,” she said.

    “This means that it should be considered a minimum. If you extrapolate that and apply it to the general population, the magnitude of the problem could be much greater.”

    Dr. Fischer said when patients do not present with psychosis, clinicians should be more careful when considering alternative diagnoses to Alzheimer’s disease.

    “Many dementia patients never receive a definitive clinical diagnosis while they’re alive, so the hope is that by understanding what factors can lead to a misdiagnosis, we can be more accurate and provide patients with the best possible care,” she said.


  9. Alzheimer’s disease risk linked to a network of genes associated with myeloid cells

    July 16, 2017 by Ashley

    From The Mount Sinai Hospital / Mount Sinai School of Medicine press release:

    Many genes linked to late-onset Alzheimer’s disease (AD) are expressed in myeloid cells and regulated by a single protein, according to research conducted at the Icahn School of Medicine at Mount Sinai and published June 19 in the journal Nature Neuroscience.

    Mount Sinai researchers led an international, genome-wide study of more than 40,000 people with and without the disease and found that innate immune cells of the myeloid lineage play an even more central role in Alzheimer’s disease pathogenesis than previously thought.

    Specifically, the research team identified a network of genes that are implicated in AD and expressed by myeloid cells, innate immune cells that include microglia and macrophages. Furthermore, researchers identified the transcription factor PU.1, a protein that regulates gene expression and, thus, cell identity and function, as a master regulator of this gene network.

    “Our findings show that a large proportion of the genetic risk for late-onset AD is explained by genes that are expressed in myeloid cells, and not other cell types,” says Alison Goate, DPhil, Professor of Neuroscience and Director of The Ronald M. Loeb Center for Alzheimer’s Disease at the Icahn School of Medicine at Mount Sinai and principal author of the study. “Dysregulation of this network is certainly a cause of Alzheimer’s, but we have more work to do to better understand this network and regulation by PU.1, to reveal promising therapeutic targets.”

    Using a combination of genetic approaches to analyze the genomes of 14,406 AD patients, and 25,849 control patients who do not have the disease, researchers found that many genes which are known to influence the age at which AD sets in, are expressed in myeloid cells. This work pinpointed SPI1, a gene that encodes the transcription factor PU.1, as a major regulator of this network of AD risk genes and demonstrated that lower levels of SPI1/PU.1 are associated with later age at onset of AD.

    To test the hypothesis that SPI1 expression levels influence expression of other AD risk genes and microglial function, the researchers used a mouse microglial cell line, BV2 cells that can be cultured in a dish. When researchers knocked down expression of SPI1, the gene that produces PU.1 in cells, they found that the cells showed lower phagocytic activity (engulfment of particles), while overexpression of SPI1 led to increased phagocytic activity. Many other AD genes expressed in microglia also showed altered expression in response to this manipulation of SPI1 expression.

    “Experimentally altering PU.1 levels correlated with phagocytic activity of mouse microglial cells and the expression of multiple AD genes involved in diverse biological processes of myeloid cells,” says Dr. Goate. “SPI1/PU.1 expression may be a master regulator capable of tipping the balance toward a neuroprotective or a neurotoxic microglial function.”

    The researchers stress that because the PU.1 transcription factor regulates many genes in myeloid cells, the protein itself may not be a good therapeutic target. Instead, further studies of PU.1’s role in microglia and AD pathogenesis are necessary, as they may reveal promising downstream targets that may be more effective in modulating AD risk without broad effects on microglial function. Increased understanding is crucial to facilitating the development of novel therapeutic targets for a disease that currently has no cure.


  10. Alzheimer’s gene associated with failure to adapt to cognitive challenge in healthy adults

    July 15, 2017 by Ashley

    From the Society for Neuroscience press release:

    Healthy adults carrying the gene APOE4 — the strongest known genetic risk factor for Alzheimer’s disease (AD) — may struggle to adapt their brain activity to increasing cognitive demands as they get older, according to a study published in The Journal of Neuroscience. This age-related effect, which was not observed in people without the risk factor, suggests that interventions targeting cognitive decline in at-risk populations may need to begin many years before any symptoms of the disease emerge in order to be effective.

    Karen Rodrigue and colleagues assessed the performance of 31 adults (ages 20-86) with APOE4 on a distance judgment task at different levels of difficulty while measuring their brain activity. Although these at-risk participants showed similar adjustment in brain activity to the difficulty of the task as non-APOE4 carrying adults of the same age, sex, and education level, this ability declined with increasing age in the individuals with APOE4. These changes occurred in the precuneus, a part of the brain implicated in the early stages of AD, and reduced modulation of this area was associated with poorer performance on the task. These findings may help to inform the identification of individuals at increased risk of developing the disease.