Introduction

There is reason for optimism about future treatment of the most common causes of dementia. Advances in understanding the molecular pathologies that underlie the most common causes of neurodegenerative dementia are rapidly being translated into new treatments. At the same time, basic investigations into the neurophysiology of synaptic transmission, neuronal growth, development and survival have identified new receptors, genes and intracellular second messenger cascades that may serve as targets for new treatments for dementia. Whereas most currently approved medications that are used to treat dementia are effective only in ameliorating the symptoms of disease, in the near future, medications that modify the course of the disease by protecting the brain from dementia-related pathology may be available. New diagnostic tests will also help to identify accurately who is likely to benefit from such treatment and monitor their treatment response. This chapter will review the currently available treatments for the most common forms of dementia, focusing on clinical syndromes that are readily identifiable by practicing clinicians, as well as new treatments that are currently under investigation or new avenues for treatment suggested by recent advances in understanding the molecular pathologies of these disorders.

Introduction

Frontotemporal lobar degeneration, formerly called Pick's disease, is a progressive dementia that is associated with focal atrophy of the frontal and/or temporal lobes. For over 100 years, the key clinical and pathological feature of this disease has been recognized to be focal, often asymmetric cortical involvement. Histopathologically, frontotemporal lobar degeneration (FTLD) is distinct from Alzheimer's disease but heterogeneous, even among similar clinical syndromes. Recently, with the advent of specialized immunohistochemical stains and insights gained from molecular genetics, it has been recognized that FTLD is closely related to, and sometimes overlaps with three other neurodegenerative diseases: corticobasal ganglionic degeneration (CBD), progressive supranuclear palsy (PSP), and motor neuron disease (MND). The central role of the microtubule-associated protein, tau, in the pathogenesis of FTLD, has led to classification as a “tauopathy.”

First description and history of FTLD

The first case of what is now called frontotemporal lobar degeneration (FTLD) was described by Arnold Pick in 1892 (Pick, 1892). His subsequent description of six similar patients emphasized a language impairment, which he termed “amnestic aphasia,” and a focal pattern of brain atrophy involving the temporal and/or frontal lobes. A lack of senile plaques and tangles in the brains of similar patients was noted by Alzheimer in 1911. He and Altman provided the first histopathological description of argyrophilic inclusions (later termed Pick bodies) and swollen achromatic cells (later termed Pick cells) (Altman, 1923).