Of the instruments reviewed, the MacArthur Competence Assessment Tools for Clinical Research and for Treatment have the most empirical support, although other instruments may be equally or better suited to certain situations. Contextual factors are important but understudied. Capacity assessment tools should undergo further empirically based development and refinement as well as testing with a variety of populations.

Neuropsychiatric symptoms (NPS) are very common in Alzheimer’s disease (AD), particularly agitation, apathy, depression, and delusions. Brain networks or circuits underlying these symptoms are just starting to be understood, and there is a growing imaging and neurochemical evidence base for understanding potential mechanisms for NPS. We offer a synthetic review of the recent literature and offer hypotheses for potential networks/circuits underlying these NPS, particularly agitation, apathy, and delusions. Agitation in AD appears to be associated with deficits in structure and function of frontal cortex, anterior cingulate cortex, posterior cingulate cortex, amygdala, and hippocampus, and may be associated with mechanisms underlying misinterpretation of threats and affective regulation. Apathy in AD is associated with frontal cortex, anterior cingulate cortex, posterior cingulate cortex, as well as orbitofrontal cortex, and inferior temporal cortex, and may be associated with mechanisms underlying avoidance behaviors.

The fornix is an integral white matter bundle located in the medial diencephalon and is part of the limbic structures. It serves a vital role in memory functions and as such has become the subject of recent research emphasis in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). As the characteristic pathological processes of AD progress, structural and functional changes to the medial temporal lobes and other regions become evident years before clinical symptoms are present. Though gray matter atrophy has been the most studied, degradation of white matter structures especially the fornix may precede these and has become detectable with use of diffusion tensor imaging (DTI) and other complimentary imaging techniques. Recent research utilizing DTI measurement of the fornix has shown good discriminability of diagnostic groups, particularly early and preclinical, as well as predictive power for incident MCI and AD. Stimulating and modulating fornix function by the way of DBS has been an exciting new area as pharmacological therapeutics has been slow to develop.

INTRODUCTION:There has been considerable progress in identifying early cognitive and biomarker predictors of Alzheimer's disease (AD). Neuropsychiatric symptoms (NPS) are common in AD and appear to predict progression after the onset of mild cognitive impairment or dementia. OBJECTIVES:The objective of the study is to examine the relationship between NPS in clinically normal older adults and subsequent cognitive decline in a population-based sample. METHODS:The Cache County Study on Memory in Aging consists of a population-based sample of 5,092 older adults. We identified 470 clinically normal adults who were followed for an average period of 5.73 years. NPS were evaluated at the baseline clinical assessment using the Neuropsychiatric Inventory (NPI). NPI domains scores were quantified as the product of frequency X severity in individual NPI domains, and then summed for the NPI-Total. Neuropsychological measures were collected at baseline and at each subsequent follow-up wave. Linear mixed effects models assessed the association of NPI-Total, NPI-Depression, and NPI-Anxiety scores (obtained at baseline) on longitudinal change in neuropsychological performance, controlling for age, sex, and education. RESULTS:Baseline Neuropsychiatric Inventory (NPI)-Total score was associated with a more rapid rate of decline in word list memory, praxis recall, and animal fluency. Baseline NPI-Depression was not associated with later decline on any of the cognitive tests, while baseline NPI-Anxiety was associated with decline in Symbol Digit Modality. CONCLUSION:In conclusion, among clinically normal older adults derived from this population-based study, total burden of NPS was associated with longitudinal cognitive decline.