AGE AT ONSET AND PATTERN OF NEUROPSYCHOLOGICAL IMPAIRMENT IN MILD EARLY-STAGE ALZHEIMER-DISEASE - A STUDY OF A COMMUNITY-BASED POPULATION

Objectives: To examine the effects of age at onset on neuropsychologic al functioning in a group of patients with probable Alzheimer disease (AD) and, within this group, to scrutinize further those patients with mild early-onset-disease as it was hypothesized that within this grou p specific patterns of cognitive impairment could he identified that c orrelated with neuropathological staging of the disease. Design: Each patient underwent an extensive neuropsychological test battery to exam ine a wide range of cognitive processes to provide information to iden tify subtypes of dementia. Setting: The Memory Clinic in the Departmen t of Geriatric Medicine, Concord Hospital, Concord, New South Wales, A ustralia. Patients: One hundred forty-five community-residing case pat ients with probable AD were studied; within this group, 51 case patien ts with mild AD and a Mini-Mental Slate Examination score greater than 19 were further examined; 36 similarly aged control patients who were part of a larger case-control study of AD in an urban population were also examined. A diagnosis of probable and possible AD was made if th e case patient had evidence of memory impairment and met criteria acco rding to the National Institute of Neurological and Communicative Diso rders and Stroke-Alzheimer's Disease and Related Disorders Association . Outcome Measures: Individual neuropsychological test scores were com pared. The tests were then grouped into 7 cognitive domains. Patterns oi early cognitive impairment were derived from these comparisons. Res ults: With an earlier age at onset, significantly more impairment on t ests of digit span and praxis was seen, while the duration of disease had no independent effect once the age at onset was fixed. Patients wi th mild early-onset dementia and a Mini-Mental State Examination score greater than 19 showed significant impairment in tests of attention, memory, frontal/executive functions, visuospatial ability, praxis, and visual agnosia compared with that shown by control patients, In this group, further analyses revealed that impairment in memory and frontal /executive functions were the earliest signs of cognitive impairment. Conclusions: These data showed that when the duration of disease was a djusted for, case patients with an earlier age at onset of AD demonstr ated significantly more impairment on tests of attention span and work ing memory (digit span), graphomotor function (copy loops), and apraxi a than those: with an alder age at onset. Our findings support the vie w that the hippocampus and its connections are affected in the early s tages of AD. The deficits in the frontal/executive functions also sugg est that a disruption of cortical pathways to the frontal lobes and th e pathological changes in this region occur early in the disease.