Neuropsychiatric Symptoms in Mild Cognitive Impairment and Dementia Due to AD: Relation With Disease Stage and Cognitive Deficits

Abstract

Background: The interaction between neuropsychiatric symptoms, mild cognitive impairment (MCI), and dementia is complex and remains to be elucidated. An additive or multiplicative effect of neuropsychiatric symptoms such as apathy or depression on cognitive decline has been suggested. Unraveling these interactions may allow the development of better prevention and treatment strategies. In the absence of available treatments for neurodegeneration, a timely and adequate identification of neuropsychiatric symptom changes in cognitive decline is highly relevant and can help identify treatment targets.Methods: An existing memory clinic-based research database of 476 individuals with MCI and 978 individuals with dementia due to Alzheimer's disease (AD) was reanalyzed. Neuropsychiatric symptoms were assessed in a prospective fashion using a battery of neuropsychiatric assessment scales: Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD), Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia (CSDD), and Geriatric Depression Scale (30 items). We subtyped subjects suffering from dementia as mild, moderate, or severe according to their Mini-Mental State Examination (MMSE) score and compared neuropsychiatric scores across these groups. A group of 126 subjects suffering from AD with a significant cerebrovascular component was examined separately as well. We compared the prevalence, nature, and severity of neuropsychiatric symptoms between subgroups of patients with MCI and dementia due to AD in a cross-sectional analysis.Results: Affective and sleep-related symptoms are common in MCI and remain constant in prevalence and severity across dementia groups. Depressive symptoms as assessed by the CSDD further increase in severe dementia. Most other neuropsychiatric symptoms (such as agitation and activity disturbances) progress in parallel with severity of cognitive decline. There are no significant differences in neuropsychiatric symptoms when comparing “pure” AD to AD with a significant vascular component.Conclusion: Neuropsychiatric symptoms such as frontal lobe symptoms, psychosis, agitation, aggression, and activity disturbances increase as dementia progresses. Affective symptoms such as anxiety and depressive symptoms, however, are more frequent in MCI than mild dementia but otherwise remain stable throughout the cognitive spectrum, except for an increase in CSDD score in severe dementia. There is no difference in neuropsychiatric symptoms when comparing mixed dementia (defined here as AD + significant cerebrovascular disease) to pure AD.

Specific agitation behaviours in dementia differentially contribute to aspects of caregiver burden

“…Restricting diagnoses can be limiting, as neuropsychiatric symptoms including agitation are seen in individuals with mild cognitive impairments and in subtypes of dementia (Alzheimer's disease, vascular dementia, Lewy Body Dementia). 40,41 The current sample of individuals presenting for an appointment at an outpatient memory clinic was comprised of largely community-dwelling individuals and did not restrict diagnoses. The three dimensions of agitation detected in this sample thus appear to apply across levels of care and diagnoses.…”

“…Although some prior work has suggested four factors (Aggressive Behaviour, Physically Non‐Aggressive Behaviour, Verbally Agitated Behaviour, and Hiding/Hoarding behaviour), 15,36 studies with these findings were largely conducted with individuals living in care facilities rather than community samples or restricted in dementia diagnoses. Restricting diagnoses can be limiting, as neuropsychiatric symptoms including agitation are seen in individuals with mild cognitive impairments and in subtypes of dementia (Alzheimer's disease, vascular dementia, Lewy Body Dementia) 40,41 . The current sample of individuals presenting for an appointment at an outpatient memory clinic was comprised of largely community‐dwelling individuals and did not restrict diagnoses.…”

Prevalence of potentially inappropriate medications among old people with major neurocognitive disorder in 2012 and 2017

“…The use of antipsychotic drugs was also associated with a lower MMSE score in the above mentioned study [ 32 ]. This can probably explain the found association between a lower MMSE score and the use of PIMs in our study, as neuropsychiatric symptoms increase as dementia progresses [ 33 ]. The increased risk of cerebrovascular events and mortality associated with the use of antipsychotic drugs is well-documented, and guidelines recommend non-pharmacological approaches prior to considering treatment of neuropsychiatric symptoms with antipsychotics [ 34 – 36 ].…”

The Role of Individual Characteristics in Predicting Short- and Long-Term Cognitive and Psychological Benefits of Cognitive Stimulation Therapy for Mild-to-Moderate Dementia

“…Severe depression has additive or multiplicative effects on cognitive deterioration ( Piras et al, 2021 ) via a two-way process that underlies the interaction between cognition and mood. This is because some cognitive dysfunctions exacerbate an individual’s susceptibility to recurrent depression, while low mood drives deficits in cognitive functioning ( Wiels et al, 2021 ). Our results are inconsistent with previous reports on the influence of individual characteristics on response to CST, however ( Aguirre et al, 2013 ; Apoìstolo et al, 2014 ; Marinho et al, 2020 ).…”