Memory Isn’t Always the First Thing to Go . . .

We usually think that loss of memory is likely to be the first sign of impending Alzheimer’s disease.  But that’s not always the case, according to a small Spanish study published in the journal Neurology.  About a third of patients with early-onset Alzheimer’s may present with other symptoms, such as behavioral problems. 

The researchers examined clinical data on 40 people who developed Alzheimer’s before age 60 and who donated their brains for postmortem examination – this allowed the diagnosis to be fully confirmed.  In addition to symptoms, family history and APOE genotype were analyzed.    

The average age at onset was 54½ (range 46 – 60), and the average duration was 11 years, with a diagnostic delay of 3 years.  As many as 15 of the 40 subjects – 37.5% - did not present with a memory deficiency.   These people had behavioral or executive function (decision-making) problems, and were significantly more likely than those with memory problems to have a delay in diagnosis (53% vs. 4%).  The 9 incorrect initial diagnoses varied quite widely.

Brain pathology in 39 of the subjects showed neurofibrillary tangles (diagnostic of Alzheimer’s, along with amyloid plaques), and 18 of the 40 had Lewy body pathology, but this was localized in most cases and wasn’t associated with a differing clinical presentation. 

Typical and atypical presentations of Alzheimer’s didn’t show significant differences in APOE genotype, with 59% having APOE genotype ε3/ε3.  Patients with a family history of Alzheimer's disease were 3 times more likely to have the abnormal APOE ε4.

This study shows that one third of patients with pathologically confirmed Alzheimer’s presented without the usual memory-loss problems.  Such patients often receive incorrect clinical diagnoses – something to be born in mind by family members and family doctors.