Neuropsychiatric symptoms in at-risk groups for AD dementia and their association with worry and AD biomarkers—results from the DELCODE study

Abstract

Background Early identification of individuals at risk of dementia is mandatory to implement prevention strategies and design clinical trials that target early disease stages. Subjective cognitive decline (SCD) and neuropsychiatric symptoms (NPS) have been proposed as potential markers for early manifestation of Alzheimer’s disease (AD). We aimed to investigate the frequency of NPS in SCD, in other at-risk groups, in healthy controls (CO), and in AD patients, and to test the association of NPS with AD biomarkers, with a particular focus on cognitively unimpaired participants with or without SCD-related worries. Methods We analyzed data of n = 687 participants from the German DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study, including the diagnostic groups SCD (n = 242), mild cognitive impairment (MCI, n = 115), AD (n = 77), CO (n = 209), and first-degree relatives of AD patients (REL, n = 44). The Neuropsychiatric Inventory Questionnaire (NPI-Q), Geriatric Depression Scale (GDS-15), and Geriatric Anxiety Inventory (GAI-SF) were used to assess NPS. We examined differences of NPS frequency between diagnostic groups. Logistic regression analyses were carried out to further investigate the relationship between NPS and cerebrospinal fluid (CSF) AD biomarkers, focusing on a subsample of cognitively unimpaired participants (SCD, REL, and CO), who were further differentiated based on reported worries. Results The numbers of reported NPS, depression scores, and anxiety scores were significantly higher in subjects with SCD compared to CO. The quantity of reported NPS in subjects with SCD was lower compared to the MCI and AD group. In cognitively unimpaired subjects with worries, low Aß42 was associated with higher rates of reporting two or more NPS (OR 0.998, 95% CI 0.996–1.000, p < .05). Conclusion These findings give insight into the prevalence of NPS in different diagnostic groups, including SCD and healthy controls. NPS based on informant report seem to be associated with underlying AD pathology in cognitively unimpaired participants who worry about cognitive decline. Trial registration German Clinical Trials Register DRKS00007966. Registered 4 May 2015.

Network analysis of impulse dyscontrol in mild cognitive impairment and subjective cognitive decline

“…Another future direction would be to analyze networks of impulse dyscontrol in MCI and SCD separately. A recent study showed that the Neuropsychiatric Inventory-Questionnaire domains associated with impulse dyscontrol -namely, agitation/aggressiveness, aberrant motor behavior and appetite disturbances (Ismail et al, 2016) -were more prevalent in MCI than in SCD (Sannemann et al, 2020). These discrepancies may be due to more substantial cognitive deficits in MCI and might even differ across MCI subgroups.…”

Plasma β-amyloid in mild behavioural impairment – neuropsychiatric symptoms on the Alzheimer’s continuum

“…6 The association between AD biomarkers and anxiety is supported in the literature, with three studies showing a relationship between decreased CSF Aβ 42 and anxiety. [47][48][49] The relationship between Aβ and depression is more uncertain. Some studies identified no relationship between decreased CSF Aβ 42 and increased depression in samples of mixed cognitive status; 47,48,50 others revealed interactions with mood disturbance in NC 49,51 and chronic subsyndromal depressive symptoms in MCI.…”

“…47–49 The relationship between Aβ and depression is more uncertain. Some studies identified no relationship between decreased CSF Aβ 42 and increased depression in samples of mixed cognitive status; 47,48,50 others revealed interactions with mood disturbance in NC 49,51 and chronic subsyndromal depressive symptoms in MCI. 52 Plasma Aβ levels have been associated with depression, such that higher baseline plasma Aβ 42 was a predictor for first depressive episode in NC older adults, and progression to AD at 5 years.…”

“…The relationship between lower CSF Aβ 42 and apathy was seen in one study 47 but not in several others. 48,49,57 However, new work demonstrated a significant association between Aβ-PET and MBI decreased motivation. 39 As well, another study determined that new-onset apathy, agitation, and irritability predicted faster progression from MCI to AD.…”

Neuropsychiatric Symptoms as Predictor of Poor Clinical Outcome in Patients With Vascular Cognitive Impairment

“…1,2 NPS are common across the clinical spectrum from mild cognitive impairment (MCI) to dementia, with 35-85% of patients with MCI and nearly all patients with dementia showing NPS. [1][2][3] NPS are associated with increased caregiver burden, higher costs of care, worse cognitive performance and poorer quality of life. [4][5][6][7] NPS also predict a worse prognosis including more rapid progression of cognitive and functional decline, earlier institutionalization and death.…”