Neuropsychiatric Issues with Cognitive Decline

April 18, 2016

Neuropsychiatric symptoms are commonly associated with mild cognitive impairment, but does amyloid pathology play a role in this relationship?

Study 1. Behavioral Correlates of Cognitive Decline

Neuropsychiatric behaviors are commonly seen with mild cognitive impairment (MCI). Researchers from the David Geffen School of Medicine, UCLA sought to investigate the prevalence of neuropsychiatric symptoms at baseline and during follow up in the presence and absence of amyloid pathology in MCI and cognitively normal subjects.

Amyloid accumulation can start up to 20 years before onset of symptoms. The newly developed positron emission tomography (PET) can measure amyloid burden in both the pre-symptomatic and symptomatic stages.

Elderly participants of the Alzheimer’s Disease Neuroimaging Initiative study (213 cognitively normal [NC] and 429 MCI) were followed longitudinally for approximately 0.5 years. [18F]-Florbetapir PET was performed on the NC and MCI subjects 0.8 and 0.4 years into the study, respectively, and 27% of NC and 50% of MCI subjects were amyloid positive. Annual neuropsychiatric inventory (NPI) data was collected at each visit and coded as present or absent.

Compared to amyloid negative NC subjects, amyloid positive NC subjects were older (76.4 vs. 71.7 years) and more likely to be APOE4 positive, yet had a lower mean total NPI score and significantly lower frequency of depression at baseline. They were, however, significantly more likely to develop depression and sleep abnormalities during follow-up.

Compared to amyloid negative subjects, amyloid positive MCI subjects were older (73.9 vs. 69.6 years), more likely to be APOE4 positive, and had a higher mean total NPI score. Amyloid positive MCI subjects had significantly greater frequency of anxiety and agitation at baseline and were significantly more likely to develop delusions, hallucinations, apathy, disinhibition, aberrant motor behavior, and appetite disturbances during follow-up.

Amyloid positive MCI subjects have a greater incidence and prevalence of neuropsychiatric behaviors. Although amyloid positive NC subjects were significantly less depressed at baseline, they developed higher rates of depression over time.

Reference: Goukasian N, et al. Behavioral Correlates of Cognitive Decline in Normal Aging and Prodromal Alzheimer’s Disease. Poster presentation P2.230, Apr 17, 2016. AAN Annual Meeting, Vancouver, British Columbia.

Study 2. Brain Amyloidosis Affects Neuropsychiatric Behaviors

The incidence and prevalence of developing neuropsychiatric behaviors, which are commonly noted in mild cognitive impairment (MCI), could be influenced by the presence or absence of amyloid pathology. Researchers from the David Geffen School of Medicine, UCLA set out to study the relationship between amyloid burden and the development of neuropsychiatric behaviors in MCI subjects over time.

A total of 429 MCI participants of the Alzheimer’s Disease Neuroimaging Initiative study were followed longitudinally for an average of 3.1 years. These subjects received [18F]-Florbetapir PET 0.4 years into the study. Half of the MCI subjects were amyloid positive. Yearly neuropsychiatric inventory (NPI) data was collected during each visit. Survival analyses were used to determine the hazard ratios for developing the most common NPI behaviors in MCI - agitation, apathy, anxiety, depression, and irritability by amyloid status.

Compared to amyloid negative subjects, amyloid positive MCI subjects were older (73.9 vs. 69.6 years), more likely to be APOE4, and had a higher mean total NPI score. They scored worse on assessment tests, including MMSE, CDR-SB, ADASCog and FAQ. Amyloid positive MCI subjects had significantly increased incidence of anxiety and agitation at baseline. Amyloid pathology was a significant risk factor for developing apathy, irritability, agitation, and depression.

In conclusion, amyloid pathology places MCI subjects at greater risk for developing neuropsychiatric symptoms.

Reference: Apostolova L, et al. Effect of Brain Amyloidosis on the Emergence of Neuropsychiatric Behaviors in MCI over Time. Poster presentation P2.232, Apr 17, 2016. AAN Annual Meeting, Vancouver, British Columbia.