Distinguishing Alzheimer Disease From Other Major Forms of Dementia

From Expert Review of Neurotherapeutics Stella Karantzoulis, PhD; James E. Galvin, MD, MPH 10/20/2011 http://www.medscape.org/viewarticle/751357?src=cmemp Abstract and Introduction Distinguishing AD Dementia From Other Major Forms of Dementia Memory Language Visuospatial Skills Attention & Executive Functions Lack of Insight/Unawareness/Anosognosia Behavior, Mood, Personality & Psychiatric Symptoms Personality Extrapyramidal Symptoms Expert Commentary & Five-year View Key Issues Abstract Alzheimer’s disease (AD) is the most common and most studied cause of dementia. Significant advances have been made since the first set of clinical criteria for AD were put forth in 1984 that are now captured in the new criteria for AD published in 2011. Key features include recognition of a broad AD spectrum (from preclinical to mild cognitive impairment to AD dementia) and requirement of AD biomarkers for diagnosis. Correctly diagnosing dementia type is increasingly important in an era when potential disease-modifying agents are soon to be marketed. The typical AD dementia syndrome has at its core, an amnestic syndrome of the hippocampal type, followed by associated deficits in word-finding, spatial cognition, executive functions and neuropsychiatric changes. Atypical presentations of AD have also been identified that are presumed to have a different disease course. It can be difficult to distinguish between the various dementia syndromes given the overlap in many common clinical features across the dementias. The clinical difficulty in diagnosis may reflect the underlying pathology, as AD often co-occurs with other pathologies at autopsy, such as cerebrovascular disease or Lewy bodies. Neuropsychological evaluation has provided clinicians and researchers with profiles of cognitive strengths and weaknesses that help to define the dementias. There is yet no single behavioral marker that can reliably discriminate AD from the other dementias. The combined investigation of cognitive and neurobehavioral symptoms coupled with imaging markers could provide a more accurate approach for differentiating between AD and other major dementia syndromes in the future. Key Issues Alzheimer’s disease (AD) is the most common form of dementia. There are 35 million individuals worldwide currently affected by the disease; and AD is projected to affect 115 million by 2050. Generally speaking, AD neuropathology initially involves medial temporal lobe structures (e.g., hippocampus and entorhinal cortex) and subsequently extends to temporal, parietal and frontal lobe association areas as the disease progresses. Neuropsychiatric symptoms are present throughout the course of AD. New diagnostic criteria for AD emphasize the importance of biomarker data in the definition of prodromal AD. The typical dementia syndrome continues to be described by prominent episodic memory impairment linked to early changes in the hippocampus and entorhinal cortex, with secondary deficits in word-finding skills, spatial cognition and executive functions. Atypical presentations of AD include posterior cortical atrophy, logopenic progressive aphasia and focal frontal variant AD. In posterior cortical atrophy, the onset is characterized by early, higher-order visual deficits and a higher density of neurofibrillary tangles in the occipital regions than in typical AD. Logopenic progressive aphasia is an atypical language variant defined as a primary phonological loop deficit leading to impaired memory, sentence repetition and comprehension, with sparse spontaneous speech and frequent prolonged word-finding pauses. Greater numbers of neurofibrillary tangles within the frontal lobes are seen in frontal variant AD, resulting in a more severe disease course. Episodic memory scores do not differ between behavioral variant frontotemporal dementia patients and AD patients, although the neural correlates of the memory impairment differs between the two patient groups. Lewy body dementia (LBD) tends to co-occur with AD in 80% of cases, with only 20% having pure LBD. Patients with pure Lewy body pathology have better verbal memory skills than those with pure AD or mixed LBD/AD. A fluctuating or step-wise course and history of strokes may help clinicians differentiate AD from mixed AD with cerebrovascular disease when their clinical profiles are otherwise indistinguishable. Subcortical vascular dementia is associated with primary deficits in information processing speed and executive functions, and secondary milder effects on memory. Personality changes are common among the dementias. They can occur in the very earliest stages of AD, prior to the onset of any obvious cognitive decline and can discriminate between AD and LBD (more passive traits in the LBD group). Personality changes appear to be more common in behavioral variant frontotemporal dementia than in AD. Current treatments for AD provide symptomatic relief either by improving symptoms or by delaying decline. Improving our understanding of the molecular mechanisms of AD has led to the identification of multiple potential targets for disease-modifying agents.