The Dementias

Daniel Z. Press

David B. Robinson

▪ INTRODUCTION

Dementia is the broad term for a set of brain disorders characterized by a loss of cognitive function sufficient to interfere with the tasks of daily life. There are several different causes of dementia, with Alzheimer’s disease being the most frequent. The specific cognitive realms that are impaired in dementia vary from patient to patient and depend in part on the specific cause of dementia. They generally include memory and often include impaired language (with naming problems or aphasia), visuospatial function, judgment, executive function, and difficulty with motor skills (apraxia). The rate of dementia increases with age, but it differs from normal aging in that at least half of all centenarians (those living to 100) do not have dementia. Further, rare genetic forms of dementia can occur as early as the 30s.

▪ EPIDEMIOLOGY

The main risk factor for dementia is age. The prevalence of dementia doubles for every 5 years after the age of 60. Approximately 2% of those 65 to 70 years of age will have dementia, but this increases to approximately 14% of those age 80 to 85 years. The estimated prevalence varies depending on the definition and ascertainment mechanism, but between 2 million and 5 million people in the United States likely are currently affected. The prevalence does not markedly differ between genders. Other risk factors depend on the type of dementia. For instance, in Alzheimer’s disease, risk factors include a family history (particularly of first-degree relatives who developed the disorder before the age of 70), vascular risk factors (e.g., diabetes and untreated hypertension), limited education, and a history of significant head trauma.

▪ TYPES OF DEMENTIA

There is no clear consensus on the prevalence of the various forms of dementia. In general, AD underlies between 60% and 70% of dementia. The next most frequent causes include dementia with Lewy bodies (or Parkinson’s-related dementia), vascular-related cognitive impairment, and frontotemporal dementia, with each accounting for approximately 5% to 15%. Less frequent causes of dementia include alcohol-related dementias, normal pressure hydrocephalus, acquired immunodeficiency syndrome (AIDS)-dementia complex, Huntington’s disease, and Creutzfeldt-Jakob disease (Table 9.1).

▪ ALZHEIMER’S DISEASE

Symptoms, Signs, and Imaging

Alzheimer’s disease (AD) is the most common form of dementia in the elderly; its prevalence increases dramatically with age, doubling for every 5 years after the age of 60. Clinically, it presents with insidious onset and gradual progression of short-term memory loss. In general, social graces are preserved. In addition to memory, patients have problems with visuospatial function
(such as learning their way around in new environments), word finding (with anomia for lowfrequency words), and complex motor functions (apraxia). Several mental status batteries have been developed to help in the diagnosis, with the Mini-Mental Status Examination being the most widely used. Unfortunately, it has relatively poor sensitivity, with particular difficulty in diagnosing highly educated patients and those early in the course of the disease. It is also not
specific for AD versus other conditions. Other batteries with higher sensitivity and specificity include the Blessed Dementia Rating Scale and Addenbrooke’s Cognitive Examination Battery. Diagnosis relies on clinical examination, although brain imaging should be performed both to rule out other conditions and to determine the pattern of atrophy. In AD, imaging generally reveals atrophy in the medial temporal lobes and in temporal-parietal cortex. Advanced imaging techniques, such as positron emission tomography (PET), are rarely indicated clinically but can be useful, particularly in patients with early-onset disease or in whom the clinical presentation is atypical.

TABLE 9.1 CLINICAL, PATHOLOGICAL, AND IMAGING FINDINGS IN THE MOST COMMON FORMS OF DEMENTIA

	AD	DLB	FTD	VCI
Cognitive Features	Early impairment of declarative memory	Early impairment in attention and visual-spatial skills	Behavioral changes and executive function deficits	Executive function deficits, depression
Fluctuations	+	+++	−	+
Neuropsychiatric Features
Visual hallucinations	+	+++; persistent, and early in disease course	−
Delusions	++	+++	++
Depression	++	+++		++
Apathy	++	++	+++(late)	++
Disinhibition	+	+	+++(early)	+
Extrapyramidal Motor Symptoms	Mild and only late in disease, paratonia (gegenhalten) and axial symptoms. Absence of rest tremor	Pronounced rigidity and bradykinesia; may be similar severity to PD, rest tremor in roughly 50%	Rare but can occur in FTDP	Impaired gait, axial signs, and upper motor neuron signs
Neuropathology	Dense, neuritic plaques, neurofibrillary tangles, sparing of primary sensory-motor cortex	Cortical and subcortical lewy bodies, frequent comorbid AD changes with plaques>tangles	Lobar degeneration, sometimes with Tau+ inclusions, often lacking distinctive histology	White matter changes, cortical strokes, ±AD changes
Neuroimaging	Neocortical atrophy sparing primary sensory-motor cortices, hippocampal atrophy	Similar to AD, though sometimes with sparing of medial temporal lobes. Impaired DA activity on f-Dopa PET	Focal atrophy of frontal or temporal lobes	White matter changes, cortical infarcts
AD, Alzheimer’s disease; DLB, dementia with Lewy bodies; FTD, frontotemporal dementia; FTDP, frontotemporal dementia with Parkinsonism; PD, Parkinson’s disease; PET, positron emission tomography; VCI, vascular cognitive impairment.