Frontotemporal Dementia

Often begins in the fifth to seventh decades; in this age group it is nearly as prevalent as AD. Unlike AD, behavioral symptoms may predominate in the early stages of FTD. Three main clinical syndromes. In the behavioral variant, the most common FTD syndrome, social and emotional systems dysfunction manifests as apathy, disinhibition, compulsivity, loss of empathy, and overeating, often but not always accompanied by deficits in executive control. Two forms of primary progressive aphasia, the semantic and nonfluent/agrammatic variants, are also commonly due to FTD. In the semantic variant, pts slowly lose the ability to decode word, object, person-specific, and emotion meaning, whereas pts with the nonfluent/agrammatic variant develop profound inability to produce words, often with prominent motor speech impairment. Any of these three clinical syndromes may be accompanied by motor neuron disease (Chap. 188 ALS and Other Motor Neuron Diseases). FTD may be sporadic or inherited. The most common autosomal dominant mutations involve the C9ORF72, GRN, and MAPT genes. Treatment is symptomatic; no therapies are known to slow progression or improve cognitive symptoms. Many of the behaviors that accompany FTD such as depression, hyperorality, compulsions, and irritability may be helped with SSRIs.

Dementia With Lewy Bodies

Characterized by visual hallucinations, parkinsonism, fluctuating alertness, falls, and often RBD. Dementia can precede or follow the appearance of parkinsonism; when it occurs after an established diagnosis of Parkinson's disease (Chap. 186 Parkinson's Disease), many use the term Parkinson's disease dementia (PDD). Lewy bodies are intraneuronal cytoplasmic inclusions. Anticholinesterase compounds often provide significant benefit due to a severe cholinergic deficit in DLB. Pts with DLB are extremely sensitive to dopaminergic medications, which must be carefully titrated; tolerability may be improved by concomitant use of a cholinesterase inhibitor. Exercise programs to maximize motor function and protect against fall-related injury, and antidepressants to treat depressive syndromes may be helpful. Antipsychotics in low doses to alleviate psychosis may be considered, although DLB pts are also extremely sensitive to these agents and may experience worsening of extrapyramidal symptoms.

Vascular Dementia

Typically follows a pattern of either multiple strokelike episodes (multi-infarct dementia) or diffuse white matter disease (leukoaraiosis, subcortical arteriosclerotic encephalopathy, Binswanger's disease) (Fig. 185-1. Diffuse White Matter Disease). A genetic disorder, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is due to a mutation in the NOTCH3 gene and presents as small vessel strokes, progressive dementia and extensive white matter disease often beginning in mid-adult life. Unlike AD, in vascular dementia focal neurologic signs (e.g., hemiparesis) are often apparent at presentation. Treatment focuses on underlying causes of atherosclerosis.

Normal-Pressure Hydrocephalus (Nph)

Uncommon; presents as a gait disorder (ataxic or apraxic), dementia, and urinary incontinence. Gait improves in some pts following ventricular shunting; dementia and incontinence do not improve. The diagnosis is difficult to make, and the clinical picture may overlap with several other causes of dementia including AD; historically many individuals treated for NPH have suffered from other dementias.

Huntington's Disease

Chorea, behavioral disturbance, and a frontal/executive disorder (Chap. 56 Tremor and Movement Disorders). Typical onset fourth to fifth decade but can present at almost any age. Autosomal dominant inheritance due to expanded trinucleotide repeat in gene encoding the protein huntingtin. Diagnosis confirmed with genetic testing coupled with genetic counseling. Symptomatic treatment of movements and behaviors; SSRIs may help depression.

Creutzfeldt-Jakob Disease

Prion disorders such as CJD are rare (∼1 per million). CJD is a rapidly progressive disorder with dementia, focal cortical signs, rigidity, and myoclonus; death in <1 year from first symptom. The markedly abnormal periodic discharges on EEG and cortical ribboning and basal ganglia hyperintensities on diffusion-weighted and fluid-attenuated inversion recovery MRI are diagnostic features. No proven treatments exist.