Age at onset and pattern of neuropsychological impairment in mild early-stage Alzheimer disease. A study of a community-based population

W. Reid, G. Broe, H. Creasey, D. Grayson, E. McCusker, H. Bennett, W. Longley and M. R. Sulway
Centre for Education and Research on Ageing, Concord Hospital, New South Wales, Australia.

OBJECTIVES: To examine the effects of age at onset on neuropsychological 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 group specific patterns of cognitive impairment could be identified that correlated with neuropathological staging of the disease. DESIGN: Each patient underwent an extensive neuropsychological test battery to examine a wide range of cognitive processes to provide information to identify subtypes of dementia. SETTING: The Memory Clinic in the Department of Geriatric Medicine, Concord Hospital, Concord, New South Wales, Australia. PATIENTS: One hundred forty-five community-residing case patients with probable AD were studied; within this group, 51 case patients with mild AD and a Mini-Mental State 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 the case patient had evidence of memory impairment and met criteria according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. OUTCOME MEASURES: Individual neuropsychological test scores were compared. The tests were then grouped into 7 cognitive domains. Patterns of early cognitive impairment were derived from these comparisons. RESULTS: With an earlier age at onset, significantly more impairment on tests of digit span and praxis was seen, while the duration of disease had no independent effect once the age at onset was fixed. Patients with 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 adjusted for, case patients with an earlier age at onset of AD demonstrated significantly more impairment on tests of attention span and working memory (digit span), graphomotor function (copy loops), and apraxia than those with an older age at onset. Our findings support the view that the hippocampus and its connections are affected in the early stages of AD. The deficits in the frontal/executive functions also suggest that a disruption of cortical pathways to the frontal lobes and the pathological changes in this region occur early in the disease.