Alzheimer disease | Plaques containing beta-amyloid peptide, and neurofibrillary tangles containing tau protein, occur throughout the neocortex. | Most common age-related neurodegenerative disease; incidence doubles every 5 years after age 60. Short-term memory impairment is early and prominent in most cases. Variable deficits of executive function, visuospatial function, and language. |
Vascular dementia | Multifocal ischemic change. | |
Dementia with Lewy bodies | Histologically indistinguishable from Parkinson disease: alpha-synuclein-containing Lewy bodies occur in the brainstem, midbrain, olfactory bulb, and neocortex. Alzheimer pathology may coexist. | Cognitive dysfunction, with prominent visuospatial and executive deficits. Psychiatric disturbance, with anxiety, visual hallucinations, and fluctuating delirium. Parkinsonian motor deficits with or after other features. Cholinesterase inhibitors lessen delirium; poor tolerance of neuroleptics and dopaminergics. |
Frontotemporal dementia (FTD) | Neuropathology is variable and defined by the protein found in intraneuronal aggregates. Tau protein, TAR DNA-binding protein 43 (TDP-43), or fused-in-sarcoma (FUS) protein account for most cases. | Peak incidence in the sixth decade; approximately equal to Alzheimer disease as a cause of dementia in patients under 60 years old. Familial cases result from mutations in genes for tau, progranulin, or others. Behavioral variant FTD Deficits in empathy, social comportment, insight, abstract thought, and executive function. Behavior is disinhibited, impulsive, and ritualistic, with prominent apathy and increased interest in sex or sweet/fatty foods. Relative preservation of memory. Focal right frontal atrophy. Association with amyotrophic lateral sclerosis. Semantic variant primary progressive aphasia Deficits in word-finding, single-word comprehension, object and category knowledge, and face recognition. Behaviors may be similar to behavioral variant FTD. Focal, asymmetric temporal pole atrophy. Nonfluent/agrammatic variant primary progressive aphasia Speech is effortful with dysarthria, phonemic errors, sound distortions, and poor grammar. Focal extrapyramidal signs and apraxia of the right arm and leg are common; overlaps with corticobasal degeneration. Focal left frontal atrophy. |