New Research Links Mild Cognitive Impairment (MCI) to Increased Isolation and Risk of Death

Two studies presented today at the Alzheimer’s Association International Conference® 2012 (AAIC®2012) in Vancouver provide evidence of connections between mild cognitive impairment (MCI) and negative health outcomes – increased isolation and death.

These studies suggest that MCI, which is too often thought of as “only a little memory loss,” is a serious condition that demands heightened physician and family member observation, personalized care, and additional research. MCI can be a precursor to Alzheimer’s disease.

One of the challenges of MCI is that the people most at risk are also more likely to simultaneously have other health conditions that require regular medication, dietary restrictions and other requirements. A person living with MCI might struggle to successfully manage those needs, and so put themselves at risk.

“While there is not currently a cure or treatment to stop or slow the progression of MCI or Alzheimer’s, early detection allows for creation of a medical team and care plan that can address these challenges. It also gives the person with the condition and their family the opportunity to take advantage of appropriate resources in the community that offer critical information and support,” said Beth Kallmyer, MSW, Vice President of Constituent Services at the Alzheimer’s Association®.

“Cognitive impairment of any kind is serious, and requires increased medical and personal attention,” said Ronald Petersen, PhD, MD, a member of the Alzheimer’s Association Board of Directors. “These studies validate the challenges of people living with MCI and their families and speak to the need for physician education to better manage their cognitive impairment and its broader impact on a person’s physical, mental and social health.”

Petersen is the Cora Kanow Professor of Alzheimer’s Disease Research, and a Mayo Clinic Distinguished Investigator, at the Mayo Clinic, Rochester, MN.

MCI Raises Risk of Death

Mindy Katz, MPH, and colleagues at Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, found that people with dementia and amnestic MCI had significantly higher risk of dying than cognitively normal people.

The researchers studied 733 individuals enrolled in the Einstein Aging Study and systematically recruited from Medicare and Registered Voter lists. The participants, who were at least 70-years-old and lived in Bronx, NY at the start of the study, had at least one annual follow up visit and were tested for the APOE-e4 gene, which is linked to increased Alzheimer’s risk. At baseline, there were 24 (3.3%) participants with dementia, 76 (10.3%) with amnestic (related to memory loss) MCI and 65 (8.9%) with nonamnestic MCI.

Participants were followed for an average of five years (up to a high of 16 years). Deaths were reported by a family member or friend designated by the participant.  This information was supplemented by searching vital records databases, such as the National Death or Social Security Death indices.

The researchers found that:

  • Compared to those who were cognitively normal, the risk of death among participants with dementia was 3.26 times higher; the risk of death among participants with amnestic MCI was 2.17 times higher.
  • Presence of APOE-4 allele, higher number of co-existing diseases/disorders, and higher degree of depression were also related to higher risk of mortality.

“In our study, amnestic MCI was associated with a doubling of the risk of death,” Katz said. “Those people with other types of non-memory thinking difficulties were not at higher risk for mortality.”

“This further supports the benefits of early detection and monitoring of cognitive impairment, not only in possibly preventing Alzheimer’s dementia, but also for prolonging life,” Katz said.

Isolation and Community Withdraw as MCI Progresses

An early sign of developing dementia may be decreased levels of activity and withdrawal from the world at large. Jeffrey Kaye, MD, and colleagues at Oregon Health & Science University, Portland, used new technologies – including small activity or motion sensors placed in the rooms of the home and contact sensors on key doors – to assess whether people with MCI spend less time out of their homes as their condition progresses over time.

“This change may initially be slow and subtle and thus difficult to detect by self-reflection or family observation,” Kaye said. “The sensor’s signals form a reporting network of typical activity that can then be analyzed to detect changes in usual established habits and behaviors.”

The researchers studied 148 people (including 28 with MCI) enrolled in the Intelligent Systems for Assessing Aging Change (ISAAC) trial. The participants had a mean age of 84.2 and were followed for up to three years. During that time, their homes were outfitted with new technologies to evaluate 24/7 activity patterns with a focus on quantity of time that was spent out of the home.

During the first month of the study, participants spent an average of 4.5 hours a day out of their home with no difference between MCI and cognitively normal participants. As the study progressed, the people living with MCI had a significantly greater decline in time spent out of the home compared to cognitively intact participants. During the last month of the trial, those without MCI left their home 3.8 hours a day on average while MCI participants only left their home 2.4 hours a day.

“These findings suggest a progressive narrowing of interaction with the outside world,” Kaye said. “This very likely diminishes quality of life and could potentially impact the progression of the disease.”

“In addition, this study method may be an innovative way to unobtrusively measure the progression of cognitive impairment and report in real time how effective treatments are in maintaining socialization and engagement with the community,” Kaye added.

This summer, the Alzheimer’s Association is conducting a pilot program in 18 U.S. cities to help people living in the early stage of Alzheimer’s remain connected and engaged. The Alzheimer’s Association Early-Stage Social Engagement Program, funded in part by the MetLife Foundation, offers a fun and comfortable way for people in the early stage of the disease to socialize with similar individuals through a variety of community-based activities and events, ranging from bowling to photography classes.

“Withdrawal from work or social activities can be a warning sign of Alzheimer’s or another form of dementia,” said Beth Kallmyer, MSW, vice president of Constituent Services at the Alzheimer’s Association. “It is important that people living with dementia remain connected to their community and have opportunities to interact socially with others facing similar challenges.”

Cognitive Status, APOE e4 Status and Risk of Death: A Report from the Einstein Aging Study

Mindy Katz, Carol Derby, Cuiling Wang, Charles Hall, Molly Zimmerman, Joe Verghese, Amy Sanders, Richard Lipton
Albert Einstein College of Medicine, Bronx, New York, United States
Presenting author e-mail:

Background: Individuals with dementia have higher mortality rates than older adults without dementia. Mortality rates in individuals with Mild Cognitive Impairment (MCI) are largely unknown and may be influenced by APOE-4 status. The goal of this study was to examine the relation of cognition on all-cause mortality taking into account APOE-4 status.

Methods: Analyses were based on 728 individuals enrolled in the EAS, who had at least one annual follow-up visit (median f/u=4.9yrs.) and information on APOE-4 status. At baseline, participants were aged 70+ and resided in Bronx, NY, a racially/ethnically diverse county in the United States. The cohort was systematically recruited from Medicare and Registered Voter lists and is representative of Bronx demographics: female=60.4%; blacks=26.6%; mean education=13.5 years [3.5]; mean age at enrollment=78.8 [5.3] years. At baseline, there were 76(10.4%) with dementia, 65 (8.9%) with amnestic MCI (aMCI), and 24 (3.4%) with nonamnestic MCI (naMCI). aMCI and naMCI were diagnosed according to updated Petersen criteria. The effect of baseline cognitive status (dementia, aMCI, naMCI and normal) on the risk of mortality was examined using Cox proportional hazards’ models, adjusting for APOE-4, gender, enrollment age, education, co-morbidities, depression, and global cognitive status. Hazard ratios used the cognitively normal group as the reference.

Results: The mortality rate in this sample was 59/1000 py. Compared to those who were cognitively normal, subjects with dementia (HR=2.51, CI 1.21-5.18, p=0.01) and aMCI (HR=2.09, CI 1.42-3.07, p=0.0002) had significantly higher risks of mortality; those with naMCI were not significantly different (HR=0.95, CI=0.58-1.66, p=0.98). The risk of mortality was not significantly different between dementia and aMCI. Presence of APOE-4 allele (HR=2.01, CI=1.13-3.56, p=0.02), higher co-morbidities (HR=1.35, CI=1.15-1.53, p=0.0001), and higher degree of depression (HR=1.10, CI=1.04-1.16, p=0.001) were also related to higher risk of mortality.

Conclusions: aMCI is a risk factor for all-cause mortality in elderly individual after adjusting for APOE-4 status and co-morbidities. This result suggests the importance of early detection of cognitive impairment for potential treatment or intervention. Not all persons defined as aMCI go on to develop clinical dementia. Future studies are needed to determine whether the relation between aMCI and death is mediated through dementia.

Community life withdrawal with MCI progression

Jeffrey Kaye, Nora Matteck, Tamara Hayes, Daniel Austin, Hiroko Dodge
Oregon Health & Science University, Portland, Oregon, United States
Presenting author e-mail:

Background: The development of MCI may be associated with decreased levels of activity or withdrawal from the world as cognitive decline progresses. This change may be difficult to detect by self-report methods. Unobtrusive home-based sensing technologies may allow the detection of subtle changes in activity indicative of MCI.

Methods: Volunteers enrolled in the Intelligent Systems for Assessing Aging Change (ISAAC) cohort study were followed longitudinally in their homes outfitted with embedded motion and contact sensors to detect 24/7 activity patterns. Time out of the home was the primary outcome of interest. Sensor data was used to sum the total time (in hours) out of house per month per participant. This time was divided by the number of valid days with monitored data per month to get average hours out of home per day per subject-month. Data were analyzed using a mixed effect model with random intercept and time effects adjusted for age, gender, education, Cumulative Illness Rating Scale and Geriatric Depression Scale score at baseline.

Results: Data from 148 participants (28 with MCI; 10 with amnestic MCI), mean age, 84.2 ± 5.0 were assessed for a mean of 2.8 ± 1.2 years.  During the first month after enrollment, participants spent a mean of 4.5 ± 3.7 hours/day out of their home; there was no difference in time out of house between MCI and cognitively normal participants during the post-baseline month. In cognitively intact participants there was no longitudinal change in time out of home. MCI participants had a significantly greater decline in time out of home over time compared to cognitively intact participants. During the last month of monitored data, cognitively intact participants left their home 3.8 hours/per day on average; MCI participants left their home 2.9 hrs/day.

Conclusions: With the progression of MCI increasingly less time is spent outside the home. This suggests a progressive narrowing of interaction with the outside world. This phenomenon may form a novel measure that can be used to unobtrusively detect early activity changes indicative of evolving MCI.


Alzheimer’s Association International Conference 2012 (AAIC)®

© 2012 Alzheimer’s Association. All rights reserved.