Dementia Syndromes in Late Life

Dementia, also now known as major neurocognitive disorder, is a syndrome involving decline in two or more areas of cognitive function sufficient to disrupt a person’s daily function. Mild cognitive impairment (MCI), also known as minor neurocognitive disorder, represents a syndrome on the continuum of cognitive decline that is a stage prior to development of functional deficits. It involves decline in one or more areas of cognitive function with independence in instrumental activities of daily living, even though they may require greater effort or compensation on the part of the individual. Neuropsychological assessment of cognition and behavior provides the most powerful biomarkers for MCI and dementia syndromes associated with neurodegenerative diseases. Discrete cognitive and behavioral patterns that occur early in the course of cognitive decline aids in differential clinical diagnosis. Additionally, all diagnostic schemes for dementia syndromes include criteria that require the appraisal of functional status, which tests an individual’s capacity to engage in decision making and carry out activities of daily living independently. Methods for assessing functional status have historically had poor reliability and validity. Nevertheless, in a clinical setting, neuropsychologists rely on a combination of self-report, collateral informants, caregiver questionnaires, and objective performance-based measures to better assess functional status. Revisions to clinical criteria for dementia reflect the adoption of new research diagnostic criteria for neurodegenerative diseases, largely driven by the National Institutes of Aging (NIA) and the Alzheimer’s Association 2011 research criteria for Alzheimer’s disease (AD). The new approach differentiates the syndromic presentations common to most neurodegenerative diseases from the etiologies (AD, LBD, VaD, etc.) based on biomarkers. In the preclinical stage, biomarker abnormalities are present years before clinical symptom manifestation. In mild cognitive impairment stage, there is a report/concern for cognitive change by the patient, informant, or clinician. There is objective cognitive decline from estimated premorbid functioning and preserved independence in functional abilities. In the dementia stage, in the context of impaired functional status, there may be prominent cognitive and behavioral symptoms that may involve impairment in memory, executive function, visuospatial functioning, and language, as well as changes in personality and behavior. The most common dementias are AD, dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VaD). All can follow a trajectory of cognitive decline similar to the aforementioned stages and are associated with neuropathogenic mechanisms that may or may not be distinctive for a particular syndrome. Briefly, Alzheimer’s dementia is associated with accumulation of amyloid plaques and tau neurofibrillary tangles. Lewy body dementias (i.e., Parkinson’s disease dementia and DLB) are characterized by Lewy bodies (alpha-synuclein aggregates) and Lewy neurites in the brainstem, limbic system, and cortical regions; DLB is also associated with diffuse amyloid plaques. Frontotemporal dementia is a conglomerate of syndromes that may overlap and include behavioral variant FTD, semantic dementia, and primary progressive aphasia (PPA). FTD dementia syndromes are marked by frontotemporal lobar degeneration (FTLD) caused by pathophysiological processes involving FTLD-tau, FTLD-TDP, FTLD-FUS, or their combination, as well as beta amyloid. Lastly, vascular dementia is associated with cerebrovascular disease that can include large artery occlusions, microinfarcts, brain hemorrhages, and silent brain infarcts; comorbid AD pathology may lower the threshold for dementia conversion. There is an emerging shift in the field toward exploring prevention strategies for dementia. Given the lack of precision in our language regarding the distinction between dementia syndromes and etiologies, we can reallocate some of our efforts to preventing dementia more broadly rather than intervening on a certain pathology. Research already supports that many individuals have biomarker evidence of brain pathology without showing cognitive impairment or even sufficient levels of pathology in the brain to warrant a diagnosis without ever displaying the clinical syndrome of dementia. That said, building cognitive reserve or resilience through lifestyle and behavioral factors may slow the rate of cognitive decline and prevent the risk of a future dementia epidemic.