Utilizing the National Alzheimer’s Coordinating Center database we analyzed 728 patients with Alzheimer's disease (AD), neuropathologically confirmed based on the CERAD criteria, comparing those (n=271) that at any moment in their evolution suffered delusions or hallucinations (P+) versus those (n=457) that did not (P-). There was no difference in AD lesion load. P+ subjects had a higher prevalence of subcortical arteriosclerotic leukoencephalopathy (SAL) and, as expected, higher Lewy body stage. Hypertension was more common in P+ patients and diabetes in subjects with both delusions and hallucinations. P+ patients tended to quit smoking later in life. The functional associations diverged: patients with delusions only had better CDR, MMSE and FAQ than P-patients, whereas the opposite was true for patients with hallucinations, whether isolated or associated with delusions. In contrast, an overlapping sample of 890 subjects from the same database with a clinical diagnosis of AD and available neuropathological exam showed greater AD load in the P+ group, a result we interpret as due to clinical misdiagnosis, since the P- group was enriched in subjects with a Braak stage I and II. We conclude that SAL is, along with Lewy bodies, a substrate for psychotic symptoms in AD, and that vascular risk factors are likely to contribute to the development of this condition.
Conflictsof Interest:
None.