TORONTO – Patients with mild cognitive impairment have a greater likelihood of having neuropsychiatric symptoms if they test positive for amyloid pathology on PET imaging, according to a study of patients in the Alzheimer’s Disease Neuroimaging Initiative.

Amyloid-positive patients were significantly more likely to develop agitation, anxiety, apathy, and other symptoms over 4 years than were amyloid-negative patients, Naira Goukasian said at the Alzheimer’s Association International Conference 2016.

“In MCI [mild cognitive impairment], we found that amyloid pathology was a significant risk factor for developing these symptoms,” said Ms. Goukasian, a researcher at the University of California, Los Angeles.

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She investigated the presence and development of neuropsychiatric symptoms in 1,077 subjects drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. The cohort comprised 275 cognitively normal subjects, 100 with subjective memory complaint, 559 with MCI, and 143 with Alzheimer’s disease. As part of ADNI, all patients had baseline neurocognitive and neuropsychiatric testing, and florbetapir F 18 (Amyvid) scans to determine brain amyloid status. Neuropsychiatric symptoms were measured with the Neuropsychiatric Inventory (NPI) and the Neuropsychiatric Inventory Questionnaire (NPI-Q) at baseline and during every annual visit. Patients were followed for up to 4 years.

At baseline, amyloid pathology was associated with some neuropsychiatric symptomatology in every group except those with subjective memory complaints.

Amyloid-positive control subjects were significantly more likely to present with depression than were amyloid-negative controls. Amyloid-positive MCI patients were significantly more likely to present with anxiety when they had amyloid pathology than when they did not. Amyloid-positive dementia patients were significantly more likely to present with apathy than were amyloid-negative dementia patients.

There were no amyloid-dependent differences in neuropsychiatric symptoms among those with subjective memory complaints.

Over the 4-year follow-up period, no new neuropsychiatric symptoms developed in the control, subjective memory complaint, or dementia groups, whether they were amyloid positive or negative.

Amyloid-positive MCI patients, however, were significantly more likely to develop new symptoms than were amyloid-negative MCI patients, including delusions (13% vs. 2%), hallucinations (8% vs. 2%), anxiety (36% vs. 25%), apathy (38% vs. 22%), agitation (36% vs. 27%), disinhibition (24% vs. 15%), irritability (46% vs. 33%), and motor disturbances (18% vs. 9%).

Ms. Goukasian did not elaborate on the pathophysiologic relationship between amyloid and these symptoms. However, a 2015 study using a similar ADNI cohort localized some of them to specific amyloid-burdened brain regions (J Alzheimers Dis. 2016;49[2]:387-98).

The study by David Bensamoun, MD, and colleagues comprised 657 ADNI participants (230 controls, 308 MCI patients, and 119 Alzheimer’s patients).

In the entire group, Dr. Bensamoun, of the Regional Memory Center, Nice, France, found positive significant correlations between anxiety and global cerebral florbetapir F 18 uptake, as well as uptake in the frontal and cingulate regions. Irritability was associated with global florbetapir F 18 uptake and increased signal in the frontal, cingulate, and parietal regions.

In the MCI subgroup, there was an association between anxiety and frontal and global cerebral uptake. In the Alzheimer’s subgroup, there was an association between irritability and parietal uptake.

“Anxiety and irritability appear to be associated with greater amyloid deposition in the neurodegenerative process leading to Alzheimer’s,” the investigators said.

Ms. Goukasian had no financial disclosures.

msullivan@frontlinemedcom.com

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