Noncognitive symptoms are common in AD patients but have been poorly studied in MCI. The subgroup of patients with amnestic MCI as well as the symptoms of depression have been the focus of most studies on the subject, said Inez Ramakers, a doctoral student at Maastricht University (the Netherlands).
In the study, 79% of the patients had at least one noncognitive symptom as defined by domain scores on the NPI. Noncognitive symptoms were clinically significant in 39% of patients, consisting mainly of apathy, depression, anxiety, and irritability.
The NPI scores did not differ significantly among the MCI subtypes. But the subjective MCI group had a significantly better NPI score and significantly less apathy than did the other three MCI subtypes combined. After 1 year of follow-up in 88 patients, NPI score has not been a significant predictor of dementia.
Atrophy on MRI Related to Subtype
Medial temporal lobe atrophy is associated with MCI subtypes and measures of cognition but not vascular risk factors, Laura van de Pol reported during the DESCRIPA session. “It has been suggested that the different types of MCI may reflect differences in underlying neuropathologies and may therefore potentially progress to different sorts of dementia,” said Ms. van de Pol of the Vrije University Medical Center, Amsterdam.
In 214 patients who underwent MRI scans at five centers, the severity of medial temporal lobe atrophy followed a significant trend from mild to more severe in subjective, nonamnestic, amnestic single-domain, and amnestic multiple-domain MCI patients. But the severity of white matter hyperintensity did not differ between the subtypes, Ms. van de Pol said.
Medial temporal lobe atrophy, but not white matter hyperintensity, was significantly and negatively correlated with cognitive testing with the Mini Mental State Examination (MMSE) word list learning, delayed word list recall, and fluency.
But vascular risk factors such as blood pressure, atherosclerosis, hypercholesterolemia, and diabetes mellitus were significantly and positively correlated with white matter hyperintensity while medial temporal lobe atrophy was not.
In a 1-year follow-up with 73 patients, medial temporal lobe atrophy was significantly correlated with a decline in delayed recall; white matter hyperintensity was not correlated with any cognitive measure.
Ms. van de Pol noted that medial temporal lobe atrophy and white matter hyperintensity did not interact with each other on cognition. Their association with patients with MCI subtypes seems to reflect different etiologies in which medial temporal lobe atrophy may be a marker of AD neuropathology, and white matter hyperintensity reflects vascular disease that does not contribute to cognitive impairment in these MCI subtypes.
Total Tau Protein Signals Decline
The total level of tau protein in an MCI subtype increases as the level of cognitive impairment rises and is correlated with worsening neuropsychology, according to a preliminary study of proteins in the cerebrospinal fluid (CSF) of 84 patients.
The percentage of patients with an abnormal total tau protein level produced a significant trend from 20% of MCI patients with subjective complaints up to about 80% of amnestic multiple-domain patients, said Peter Jelle Visser, M.D., also of Maastricht University. Levels of amyloid β 1–42 and phosphorylated tau did not follow a significant trend.
CSF levels of total and phosphorylated tau correlated significantly with declining performance on the MMSE and tests of delayed recall, fluency, and trail making. Follow-up at 1 year in 33 patients (27 nondemented, 6 AD) showed that the increase in levels of total and phosphorylated tau was significantly higher in patients with AD than in those without dementia.
To further investigate the possibility that even the 20% of subjective MCI patients with abnormal CSF protein levels could develop dementia in follow-up, Dr. Visser suggested that “other studies should not only focus on amnestic MCI but also on the other forms of MCI.”
