Potential New Alzheimer’s Disease Diagnostic Criteria Determined

Data presented at the Alzheimer’s Association’s  International Conference on Alzheimer’s Disease 2010 hopes to change the way physicians diagnose Alzheimer’s disease as well as provide a diagnosis well before symptoms are evident.  The Alzheimer’s Association wants to develop new diagnostic criteria based on the current theory that Alzheimer’s disease occurs before patients become symptomatic. Earlier detection means earlier, effective risk reduction methods and better treatment options for all patients.

The workgroups focused on three areas: Alzheimer’s disease dementia, mild cognitive impairment (MCI) with Alzheimer’s disease, and pre-clinical Alzheimer’s disease. The Alzheimer’s disease dementia group is revising the existing diagnostic criteria to include biomarkers and other assessment methods to aid diagnosis. The MCI with Alzheimer’s disease group is reviewing and refining the MCI criteria in an effort to better indicate cognitive change before dementia as well as to better differentiate between MCI and Alzheimer’s disease. The pre-clincial group is focusing on identifying the best methods of assessment to better predict a person’s risk for developing Alzheimer’s disease.

Once this criteria is validated, it needs to be flexible enough for use by health care providers that do not have access to advanced imaging, cerebrospinal fluid measures, and neuropsychological testing.

The results are only preliminary and still need to be systematically validated via incorporation of this criteria into clinical trials.

For more information on the Alzheimer’s Association, please visit www.alz.org/icad. –CN

Obesity-related Gene Increases Risk for Incident Alzheimer’s Disease

The fat mass and obesity-associated (FTO) gene, which related to obesity, affects body mass index (BMI), risk for diabetes, and leptin levels. A study by Caroline Graff, MD, PhD, at the Karolinska Institutet in Sweden, and colleagues, found that these vascular risk factors may also play a role in the development of Alzheimer’s disease and dementia. The risk for Alzheimer’s disease could be doubled when certain variants of both FTO and the Alzheimer’s disease risk gene, apolipoprotein E (APOE), are present.

The aim of the study was to examine the direct role of the FTO gene on Alzheimer’s disease and dementia risk in the elderly. BMI, diabetes, cardiovascular diseases (CVD), and physical inactivity were also reviewed as possible modifiers to the association. The researchers also assessed possible interaction with APOE, which plays a role in the development of Alzheimer’s disease as well as vascular risks.

Data was gathered from a prospective population-based study called the Kungsholmen project, which followed 1,003 dementia-free Swedish adults ≥75 years of age for 9 months to detect incident Alzheimer’s disease and dementia cases, as classified by Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised criteria. Participants were genotyped for the FTO polymorphism (rs9939609) and APOE e4 (rs429358) on DNA that was sampled at baseline.

The study found—after adjustment for age, gender, education, and APOE genotype, as well as additional adjustment for diabetes, BMI, CVD, and physical inactivity—that carriers with the AA gene variant in the FTO gene had an increased risk for developing Alzheimer’s disease (RR 1.58, 95% CI: 1.11-2.24) and dementia (RR 1.48, 95% CI: 1.09-2.02) when compared to carriers with the TT genotype. Dementia risk was increased in carriers of FTO-AA and APOE e4.

Although more research is needed to confirm these results, the study shows the importance of metabolic dysregulation on the development of Alzheimer’s disease and dementia. Greater understanding of the genetics and other causes of Alzheimer’s disease will provide additional targets for therapies and prevention strategies.

Funding for this research was provided by Anslag forskning och utveckling (FAS, Stockholms läns landsting), Forskningsrådet för Arbetsliv och Socialvetenskap (Sweden), the Gamla tjänarinnor Foundation, the Gun & Bertil Stohne’s Foundation, the Karolinska Institutet’s Faculty funding for postgraduate students, the Swedish Brain Power Initiative, the Swedish Research Council in Medicine, the Marianne and Marcus Wallenberg Foundation, and the Swedish Alzheimer Foundation. (AAICAD 2010. Presentation #O2-06-06). –DC

Alzheimer’s Patients Have Greater Risk for Seizures, Anemia

The findings of two separate studies suggest that an Alzheimer’s disease diagnosis is associated with health conditions such as seizures and anemia.

H. Michael Arrighi, PhD, at Janssen Alzheimer Immunotherapy Research & Development, and Nicole Baker, MPH, at Pfizer, and colleagues, used medical records from ~400 primary practices in England to estimate the incidence rate of seizures in Alzheimer’s disease patients. The Alzheimer’s disease population in this analysis numbered 14,838 people ≥50 years of age. The Alzheimer’s disease cohort was compared to a randomly selected age- and sex-matched non-Alzheimer’s disease cohort.

Over an average period of 2.3 years for Alzheimer’s disease patients and 3.4 years for non-Alzheimer’s disease comparisons, the rate of seizures per 1,000 people numbered 9.1 and 1.4, respectively, an incidence rate 6.4 times higher for the Alzheimer’s disease group.

In a second study, Noel Faux, PhD, at the Mental Health Research Institute in Parkville, Australia, and colleagues, took a closer look at the hypothesis stating that iron accumulates in the tau tangles in the brains of Alzheimer’s disease and mild cognitive impairment (MCI) patients. They examined whether elevated iron levels in the brains of Alzheimer’s disease patients could appear in plasma iron level analyses. The researchers took hemoglobin and iron measurements, among other blood-based assessments, in 1,112 subjects comprising 211 Alzheimer’s disease patients, 133 MCI patients, and 768 healthy controls. Diet, medications, short- and long-term memory status, and global cognition were also assessed.

Compared to age- and sex-matched controls, Alzheimer’s disease patients had significantly lower levels of hemoglobin, mean cell hemoglobin concentration, and packed cell volume. These data concurred with a significantly higher erythrocyte sedimentation rate in the Alzheimer’s disease group. Anemic patients also stood a greater risk of Alzheimer’s disease (OR 2.56), and Alzheimer’s disease patients had an increased risk of anemia (OR 2.61), although iron intake did not vary between these two groups. (AAICAD 2010. Arrighi Presentation #O2-06-04; Faux Poster #P3-261). –LS

Outpatient Healthcare Costs May Be Reduced Following Screening and Diagnosis of Cognitive Impairment

Dementia is a common, costly, and underrecognized problem in the elderly. As severe loss of memory and other mental abilities interfere with daily life, it is important to more adequately detect and diagnose dementia as well as to provide necessary care management.

A study by J. Riley McCarten, MD, at the VA Medical Center in Minneapolis, Minnesota, and colleagues, analyzed results from the Dementia Demonstration Project (DPP), an interdisciplinary effort led by the Geriatric Research, Education and Clinic Center at the Minneapolis VA Medical Center. The aim of the project was to identify, evaluate, diagnose, and manage cognitive impairment (CI) in primary care, and to provide information, support, and care coordination for veterans newly diagnosed with dementia. Advanced practice registered nurses specially trained in dementia acted as Dementia Care Coordinators in primary care clinics at seven VA Medical Centers.

Veterans ≥70 years of age who were medically stable, able to comply, and without a prior diagnosis of CI or other dementia were screened uing the Mini-Cog memory test during each routine primary care clinic appointment. Of the 8,278 veterans screened, 26% failed; 34% of those who failed the test returned for a comprehensive evaluation, and of them 95% were diagnosed with CI, including 76% with dementia.

Data from 1 year prior to and 1 year after CI diagnosis were analyzed in 347 DDP patients and 1,261 non-DDP patients. Median DDP outpatient care costs saw a decline of >54% (-$5,519), compared with a 25% decline (-$1,759) of those diagnosed in non-DDP clinics. Median number of line-item outpatient costs declined by 53% (-54) in DDP patients compared with 32% (-21) in non-DDP patients.

The program aimed at providing family members with information about dementia, at ensuring that patients were physically active and socially engaged, and at providing caregivers with all necessary support. The study demonstrated that diagnosing CI was associated with a decrease in total and line-item healthcare costs in the year after diagnosis compared to the year prior. More dramatic decreases were seen in patients who were identified through cognitive screening and had subsequent case management available by a dementia care team.

Funding for this research was provided by the Strategic Initiative and the Veterans Integrated Service Network 23. (AAICAD 2010. Presentation #O4-04-04). –DC

Psychiatric dispatches is written by Dena Croog, Christopher Naccari, and Lonnie Stoltzfoos.