Very early diagnosis is an area of intense research, and it is still too early to tell whether careful interviewing, neuropsychological testing, brain imaging, or spinal fluid tests will prove the most sensitive and reliable early indicators of incipient AD. However, research teams around the world now regularly report promising advances.

To diagnose AD at earlier stages, specialists across the United States are increasingly emphasizing an approach elaborated at Washington University, St. Louis, which relies heavily on interviews with an informant. In this method, a neurologist conducts a lengthy interview with a spouse or caregiver to establish a detailed account of specific, recent, personal events in the past days, weeks, and months of the patient's life. Then the neurologist quizzes the patient for his/her memory of those events. Results are then integrated with other diagnostic assessments into a score on a clinical dementia rating scale (CDR), and a diagnosis of preclinical, or incipient AD may be given.

Other centers focus on a diagnostic category called mild cognitive impairment (MCI, Petersen, 2004). This is a similar concept. Using a slightly different combination of assessments and terminology, MCI classifies very early symptomatic stages that are not yet severe enough to constitute AD as defined in the NINCDS/ADRDA or DSM-IV criteria (Markesbery et al., 2006).

Research neurologists debate the pros and cons of these two approaches, but for practical purposes, the differences are a matter of definition and labeling more than they represent truly different disease states. That is because people diagnosed as having a type of MCI with significant memory loss, called amnestic MCI, are increasingly viewed as probably having AD at a very early stage. In other words, the same underlying disease process is thought to be at work in a person diagnosed with amnestic MCI and in a person diagnosed with preclinical AD who has a low CDR score of 0.5. In both preclinical AD and MCI, observations from informants are vitally important for a correct diagnosis. In early onset AD, those informants often are colleagues at work (provided the patient has given the neurologist permission to speak with selected coworkers) or spouses. The important point for families who suspect early onset AD in a loved one is to seek care from specialists with extensive experience diagnosing AD, who will have access to the latest information and tools for detecting the subtle changes that signal the oncoming disease. The Alzheimer Disease Education and Referral (ADEAR) service is a good resource for locating such specialists in your area.—Gabrielle Strobel.

Further reading:
Morris JC, Storandt M, Miller JP, McKeel DW, Price JL, Rubin EH, Berg L. Mild cognitive impairment represents early stage Alzheimer disease. Arch Neurol. 2001 Mar 1;58(3):397-405. Abstract

Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006 Mar 1;5(3):228-34. Abstract

Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol. 2007 Mar ;64(3):343-9. Abstract

Graff-Radford NR, Crook JE, Lucas J, Boeve BF, Knopman DS, Ivnik RJ, Smith GE, Younkin LH, Petersen RC, Younkin SG. Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch Neurol. 2007 Mar ;64(3):354-62. Abstract

NEXT: Interview: A Diagnostic Odyssey