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Andrea Bozoki, MD; Bruno Giordani, PhD; Judith L. Heidebrink, MD; Stanley Berent, PhD; Norman L. Foster, MD

Arch Neurol. 2001;58:411-416.

Background  Some elderly individuals exhibit significant memory deficits but do not have dementia because their general intellect is preserved and they have no impairments in everyday activities. These symptoms are often a precursor to Alzheimer disease (AD), but sometimes dementia does not occur, even after many years of observation. There is currently no reliable way to distinguish between these 2 possible outcomes in an individual patient. We hypothesized that clear impairments in at least 1 cognitive domain in addition to memory would help identify those who will progress to AD.

Objective  To determine whether nondemented patients with impairments in memory and other domains are more likely than those with memory impairment alone to develop AD.

Design and Methods  In a retrospective study, we evaluated 48 nondemented, nondepressed patients with clinical and psychometric evidence of memory impairment who were followed up for 2 or more years. Age-adjusted normative criteria were used to identify whether additional impairments were present in language, attention, motor visuospatial function, and verbal fluency at this initial evaluation. The presence or absence of dementia after 2 years and at the most recent neurological evaluation was compared in subjects with normal scores in all 4 of these cognitive areas apart from memory (M-) and those with impairment in 1 or more of these areas (M+). Outcomes were adjusted for age, intelligence at initial evaluation, and years of education.

Results  Of the 48 nondemented patients with memory loss, 17 met M- criteria, leaving 31 in the M+ group. Deficits in block design were the most frequent abnormality other than memory loss. At the 2-year follow-up, 1 M- subject (6%) had progressed to AD, whereas 15 (48%) of the M+ group had progressed to AD (P = .003). At the most recent follow-up (mean ± SD, 4.0 ± 2.0 years), 4 (24%) of the M- patients progressed to AD compared with 24 (77%) of the M+ patients (P<.001).

Conclusions  Among nondemented elderly patients, memory loss alone rarely progresses to dementia in the subsequent 2 years. However, the risk of dementia is significantly increased among patients with clear cognitive impairments beyond memory loss. Further study is needed to determine whether patients with impairments limited to memory loss have a distinctive clinical course or pathophysiology.

From the Departments of Neurology (Drs Bozoki, Heidebrink, and Foster) and Psychiatry (Drs Giordani and Berent), University of Michigan Medical Center, and Geriatric Research Education and Clinical Center, Ann Arbor Veterans Affairs Medical Center (Dr Heidebrink), Ann Arbor.

Corresponding author and reprints: Andrea Bozoki, MD, Department of Neurology, University of Michigan, TC1913A, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0322 (e-mail: abozoki{at}med.umich.edu).

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