Neuropsychiatric Symptoms and Functional Decline in Alzheimer's Disease and Lewy Body Dementia

Miguel Germán Borda, MD; Dag Aarsland, MD, PhD; Diego Alejandro Tovar-Rios, MSC; Lasse M. Giil, MD, PhD; Clive Ballard, MD, PhD; Maria Camila Gonzalez, MD; Kolbjørn Brønnick, PhD; Guido Alves, MD, PhD; Ketil Oppedal, PhD; Hogne Soennesyn, MD, PhD; Audun Osland Vik-Mo, MD, PhD


J Am Geriatr Soc. 2020;68(10):2257-2263. 

In This Article


Here we studied the longitudinal association of total NPSs and functional decline in patients with AD and LBD. The main finding was that in both groups, the longitudinal course of NPSs was associated with functional decline. In addition, in AD, the baseline total NPI score predicted future functional decline. These associations were independent of cognition, age, sex, and comorbidity, and further underline the importance of NPSs in people with dementia.

Behavioral and psychological symptoms of dementia are highly disabling, resulting in caregivers' burnout and increased rates of NH admissions and poor outcomes.[14,33] We show an association of NPSs with functional deterioration, which is independent of cognition.

Previous studies of the association of NPSs and functional decline have focused on specific symptoms rather than the total symptom load. For example, several studies have found that psychotic symptoms (i.e., delusions and hallucinations) are associated with a more rapid functional decline in AD,[10,15,34] and other studies reported that depressed mood, agitation/aggression, anxiety, and apathy[15,34,35] may be also associated with functional decline. Furthermore, You et al found that sleep nighttime behavior disorders also predicted functional trajectories in AD.[17] However, most previous analyses have not considered the important interaction when NPS domains are analyzed together in the same model and the risk of collinearity.

People with more severe NPSs showed a stronger association with functional deterioration. Screening of NPSs may help identify patients with especially high risk of a more severe course.[36,37] These patients could be more vulnerable to polypharmacy, institutionalization, poor control of comorbidities, lack of mobility/immobilization, frailty, and isolation. Other potential explanations are more stress and disruption due to NPSs, leading to functional deterioration. It is also possible that those with more NPSs have a more widespread and rapidly progressing neurodegenerative disease. Specially, LBD patients could be more susceptible to functional decline due to features of the disease other than NPSs, such as attentional fluctuations. We have shown that attention is associated with ADL in PDD,[38] as well as sleep disorders and parkinsonism.[13,39] The association between longitudinally assessed NPSs and functional trajectory is in line with the previously evidenced unstable course of NPSs observed in both AD and LDB,[8] and underline why regularly and structured assessments of NPSs are important. Current data imply that both prevention and treatment of NPSs may be beneficial also with regard to functional decline.

Our research may have a potential recruitment bias because of referrals of primary care patients, which may have led to an increased number of patients with complicated dementia or NPSs. However, general practitioners were encouraged to refer any patients with suspected dementia, and patients were included from psychiatric, neurological, and geriatric clinics. We used the NPI to assess NPSs. Although the NPI assesses several relevant NPSs commonly occurring in people with dementia, it does not capture the total spectrum of NPSs, with symptoms such as obsessions and compulsions not being assessed. In addition, the NPI is entirely based on caregiver reports and thus not the subjective experiences of the patients. Besides, interactions of NPSs with medications were not evaluated. We did not standardize drug and psychosocial management, which might have influenced the course. The restrictive use of psychotropics in the DemVest study is consistent with the most recent guidelines. Finally, there were dropouts and an expected high mortality, which led to relatively small sample size, particularly in the LBD group, which may have confounded the observed course of functional performance. However, our study has several important strengths, including long follow-up time, yearly assessments with structured instruments, and high completeness of data, except dropout due to death. This is one of the few long-term studies assessing daily functioning in LBD. The diagnostic procedures were rigorous, and high accuracy has been demonstrated with neuropathological diagnosis for AD and LBD.[25] A unique aspect of our study is the inclusion of patients with LBD. This is particularly relevant given the high severity of NPSs in these patients.[8,40]

Effect modification was checked by introducing interaction between dementia groups and NPI. Both models did not show relevant differences (baseline P = .9899 and longitudinal P = .5043).

This study demonstrates the functional implications of NPSs in people with AD and LBD. Therefore, a more comprehensive approach, which includes prevention, early identification, education, and interventions from a pharmacological and a nonpharmacological perspective, concerning NPSs could impact the functional prognosis of people with these dementias.

NPSs should be identified at diagnosis and tracked in the follow-up, particularly in those patients having certain NPSs where intervention might help to improve functional outcomes in the future.