Metabolic Disorders Linked to Cognitive Decline

Allison Gandey

March 17, 2009 — Evidence is mounting that metabolic and neurological diseases share common risk factors. According to several reports in the March issue of the Archives of Neurology, metabolic disorders may influence the development of Alzheimer's disease and other forms of dementia.
"Preventing heart disease, stroke, and diabetes — or making sure these conditions are well managed in patients diagnosed with them — can potentially slow the disease progression of Alzheimer's," Yaakov Stern, PhD, from the Gertrude H. Sergievsky Center at Columbia University, in New York, said in a news release.
Dr. Stern is senior author of a paper in the issue exploring the effect of vascular risk factors on cognitive impairment.
In a review article in the same issue, Suzanne Craft, PhD, from the Veterans Administration Puget Sound Health Care System, in Seattle, Washington, reports, "In recent years, a rapidly increasing number of studies have focused on the relationship between dementia and metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia."
She points out that etiological heterogeneity and comorbidity pose challenges for determining relationships among metabolic disorders. "The independent and interactive effects of brain vascular injury and classic pathological agents such as beta amyloid have also proved difficult to distinguish in human patients, blurring the lines between Alzheimer disease and vascular dementia."
Few treatment options are available to improve prognosis. Dr. Stern and his team question whether controlling vascular conditions may be 1 way of delaying cognitive decline.

Control Vascular Risk Factors and Delay Alzheimer's?
The investigators hypothesized that vascular factors such as heart disease, stroke, diabetes, hypertension, smoking, and blood lipid levels may predict the progression of Alzheimer's disease.
Led by Elizabeth Helzner, PhD, also from Columbia University, the group studied 156 patients followed for a mean of 3.5 years. Participants were from the Washington Heights and Inwood Columbia Aging Project, a multiethnic, community-based, prospective study of aging in northern Manhattan.
Researchers found that patients with a history of diabetes and elevated levels of cholesterol, especially LDL cholesterol, had faster cognitive decline. In fact, each 10-U increase in cholesterol and LDL cholesterol was associated with a 0.10-standard-deviation decrease in cognitive score per year of follow-up (P < .001 for total cholesterol; P = .001 for LDL cholesterol).
Investigators found that a history of heart disease and stroke were associated with cognitive decline only in carriers of the APOE e4 allele.
"These findings indicate that controlling vascular conditions may be 1 way to delay the course of Alzheimer's, which would be a major development in the treatment of this devastating disease," Dr. Stern said.
In another study published in the issue, investigators show that obese middle-aged adults and underweight elderly people have an increased dementia risk.

Fluctuations in Weight May Boost Dementia Risk
Using data from the Cardiovascular Health Study, researchers studied the body-mass index (BMI) of participants at mid- and late life. Patients were from a community-dwelling sample at 4 US sites.
Investigators included 2798 people. Of these, 480 had incident dementia, 245 had Alzheimer's disease, and 213 had vascular dementia.
They found that middle-aged patients who were obese had an increased risk for dementia (BMI >30 vs normal-weight BMI 20 to 25), adjusted for demographics (hazard ratio, 1.39; 95% CI, 1.03 – 1.87) and for cardiovascular risk factors (hazard ratio, 1.36; 95% CI, 0.94 – 1.95).
These results help explain the 'obesity paradox.'
But the risk estimates were reversed in assessments of late-life BMI. Underweight people, those with a BMI of less than 20, had an increased risk for dementia (hazard ratio, 1.62; 95% CI, 1.02 – 2.64). Surprisingly, being overweight later in life was not associated with an increased risk (hazard ratio, 0.92; 95% CI, 0.72 – 1.18), and being obese reduced the risk for dementia (hazard ratio, 0.63; 95% CI, 0.44 – 0.91).
"These results help explain the 'obesity paradox,' " the researchers, led by Annette Fitzpatrick, PhD, from the University of Washington, in Seattle, write. "Differences in dementia risk across time are consistent with physical changes in the trajectory toward disability."
These findings suggest that the predictive ability of BMI changes across time, they note
"Weight loss occurs with comorbidities at older ages and is often reflective of poor health," write Dr. Fitzpatrick and her team. "Weight loss, along with psychological, behavioral, and mobility problems, is 1 of the principal manifestations of Alzheimer's disease. Weight loss may predate dementia onset by as much as 10 years."
The researchers conclude: "These results reinforce the necessity of monitoring weight loss closely in older adults."
The researchers have disclosed no relevant financial relationships.

Arch Neurol. 2009;66:300-305 Abstract, 336-342 Abstract, 343-348. Abstract