Neuropsychological Data Endorse Preclinical AD

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AT THE ALZHEIMER'S ASSOCIATION INTERNATIONAL CONFERENCE 2012

VANCOUVER, B.C.--The first evidence of emerging Alzheimer's disease surfaces at least 1 decade before the onset of the disorder, based on new neuropsychological data reported at the meeting.

So far, though, there is no single test or battery of tests that can be performed at baseline to predict preclinical Alzheimer's disease, acknowledged lead investigator Dr. Richard J. Caselli. "Cross-sectional comparisons of the most sensitive longitudinal measures still fail to distinguish preclinical-stage Alzheimer's [having epsilon 4 homozygotes] from normal [epsilon 4 noncarriers]."

The early diagnosis glass might still be half full, however. The study, designed over a decade ago, relied on conventional measures that are part of most clinical neuropsychological batteries. "One gets the sense that there are newer, better tests ... that might have picked up cross-sectionally the differences," said Dr. Howard Chertkow of McGill University in Montreal.

Yet, threads of data are coming together to make possible early diagnosis and potentially early intervention for slowing the progression of Alzheimer's disease.

"The concept of preclinical Alzheimer's disease has gotten a lot of traction in the past year or two, particularly with the advent of [cerebrospinal fluid] levels of biomarkers and amyloid antigen. ... Putting these pieces together--the imaging, the pathology, the cognition--we know that there is this entity now that has been recognized as preclinical Alzheimer's disease," said Dr. Caselli of the Mayo Clinic in Scottsdale, Ariz.

Dr. Caselli reported longitudinal data from 813 cognitively healthy adults who underwent serial assessments every 1-2 years for an average of 8 years. Study participants underwent an extensive neuropsychological battery that tested memory, executive function, language, and visuospatial ability.

Participants who carried any copies of the apolipoprotein E (apo E) epsilon 4 allele, a risk factor for Alzheimer disease, had more rapid declines in performance on some tests of memory and were less proficient at learning new information than were participants who lacked the apoE epsilon 4 allele.

"Preclinical Alzheimer's begins in [epsilon 4] carriers on average in the 50s, with a clinical lag time of 10-15 years," Dr. Caselli said at the conference.

"Extrapolating from these group analyses," Dr. Caselli said, " neuropsychological assessment of preclinical Alzheimer's disease in individuals might be based upon either longitudinal memory performance (particularly verbal memory) or some form of cognitive stress test, like . …