Dementia and Memory Loss



Dementia and Memory Loss


Lawrence S. Honig



INTRODUCTION

Dementia is characterized by intellectual deterioration, with concomitant decline in independence and daily social or occupational functions.

With different dementia disorders, various cognitive domains may be dominantly affected including memory, orientation, abstraction, learning ability, visuospatial perception, language functions, constructional praxis, and higher executive functions such as planning, organizing, and sequencing activities. By past convention, now loosened, dementia was not typically diagnosed in the presence of impairment of only a single domain, requiring significant involvement of at least two domains.

In the Diagnostic and Statistical Manual of Mental Disorders (DSM) versions I through IV-TR, there was a requirement that at least one of the affected cognitive domains be memory. This requirement, designed originally for Alzheimer disease (see Chapter 50), has been dropped in the most recent DSM-5 with recognition of various dementias that do not initially or primarily involve memory, for example, frontotemporal dementia (see Chapter 51).

Dementia is diagnosed only when there is some significant decline in ability to function at home or at work. Dementia may be distinguished from mild cognitive impairment (MCI; see Chapter 49) in the requirement of significant impairment of independence in everyday activities such as occupational, social, or self-maintenance activities. The patient with MCI may have cognitive impairment in one or more domains, but this dysfunction is insufficient to cause functional impairment. For this reason, detailed analysis of the patient’s need for help from others for simple activities of daily living (e.g., toileting, food preparation, shopping, housework) is crucial.


TERMINOLOGY AND CLASSIFICATION

In the most recent DSM-5, the American Psychiatric Association has eliminated the term dementia in favor of Major Neurocognitive Disorder. However, the distinction between dementia and MCI remains, as it pertains to functional status. The DSM-5 formulation is of “major” and “minor” neurocognitive disorders, depending on the degree of functional impairment. The major neurocognitive disorders are what were termed dementias, and the minor neurocognitive disorders represent types of MCI that may be precursors to dementias (see Chapter 49). The new DSM-5 criteria permit both major and minor neurocognitive disorders to involve impairment with even a single domain but keep the distinction as to presence or absence of functional impairment. Despite the revised terminology of the DSM-5, the use of the terms dementia and MCI are likely to persist in both neurologic and lay parlances.

Dementia can be classified in various ways. The oldest system was to classify dementias as presenile (i.e., young at onset) or senile (i.e., old at onset). This is not of any present use because each of the dementing disorders can have first symptoms arise over a wide range of age at onset. Older texts also referred to treatable versus untreatable dementias, with the treatable group including conditions such as hypothyroidism or B12 deficiency and the untreatable group including Alzheimer disease and other degenerative conditions. Such a classification is not presently useful because treatment is being developed for dementing disorders previously deemed untreatable. For example, as of 2015, five different drugs are approved in the United States, per U.S. Food and Drug Administration labeling, specifically for treatment of Alzheimer disease (see Chapter 50). Another dichotomous categorization of dementia proposed separating disorders into those of genetic origin and others of “sporadic” nature. However, this also has proven to be of minimal use because most dementia disorders may occur in either inherited (familial) forms or sporadic varieties. Dividing dementias into those with principally cortical or subcortical features, or into those with or without motor signs, has not proven useful for diagnosis, prognosis, or treatment and management. Thus, the most useful categorization of dementias is now based on the pathoetiologic basis of disease (Table 11.1). With clinicopathologic correlation, it is now usually possible to provide a specific diagnosis during life with 75% to 85% accuracy. It is important to recognize that even with an excellent clinical history and examination and auxiliary testing, clinical diagnosis of the dementia pathoetiology will not have perfect sensitivity or specificity.

Some patients have subjective complaints of cognitive disturbance, which is objectively verifiable but insufficient in either severity or functional disturbance or activities of daily life to meet criteria for dementia. In these cases, a diagnosis of MCI may be made, with specification of the involved cognitive domains (memory, language, visuospatial, executive, or attention). A large proportion of persons with MCI will develop some form of dementia within 5 to 7 years, with an annual rate of conversion of MCI to dementia as high as 10% to 15%.


CAUSES OF DEMENTIA

Dementing disorders are best etiologically classified as endocrine, metabolic, cerebrovascular, inflammatory, infectious, structural, or neurodegenerative (see Table 11.1). The last category is characterized by absence of the prior-listed etiologies.


NEURODEGENERATIVE DEMENTIAS

In the United States, the most common causes of dementia of the elderly are neurodegenerative. These include Alzheimer disease, Lewy body dementia, frontotemporal dementia, and Creutzfeldt-Jakob disease (CJD).


Alzheimer Disease

Alzheimer disease (see Chapter 50), with prominent memory and language impairment, is the most frequent form of dementia, accounting in the elderly for about 80% of the total number of patients in autopsy, clinical, or population-based series (Table 11.2). Structurally, it is marked by temporal and parietal degeneration.
Molecularly, it is characterized as an “amyloidopathy” because the most specific hallmark is abnormal deposits of β-amyloid in plaques, in addition to the less specific hyperphosphorylated tau protein evident in neurofibrillary tangles.








TABLE 11.1 Dementias Categorized by Pathoetiologic Basis




























































Primary Neurodegenerative Disorders


Alzheimer disease (AD)


Lewy body disorders



Dementia with Lewy bodies (DLB)



Parkinson disease dementia (PDD)


Frontotemporal dementias (FTD)



Behavioral variant frontotemporal dementia (bvFTD)



Progressive nonfluent aphasia (PNFA)



Frontotemporal dementia with motor neuron disease (FTD-ALS, FTD-MND)



Progressive supranuclear palsy (PSP)



Corticobasal degeneration (CBD)


Huntington disease (HD)


Wilson disease (WD)


Creutzfeldt-Jakob disease (CJD) and other prion diseases


Hippocampal sclerosis


Others: British familial dementia, HDLS, others


Vascular dementias: multi-infarct dementia, Binswanger disease, CADASIL


Immune-mediated encephalitides: NMDARAE, VGKCAE, others


Demyelinating dementias: multiple sclerosis, adreno- and metachromatic leukodystrophies


Inflammatory dementias: CNS vasculitides, Behçet syndrome, systemic lupus


Infectious dementias: neurosyphilis, neuroborreliosis, HIV dementia, others


Neoplastic dementias: tumors, carcinomatous meningitis, paraneoplastic syndromes


Metabolic or endocrine dementias: B12 or rarer vitamin deficiencies, hypothyroidism


Structural dementias: hydrocephalus, brain trauma


FTD-ALS, frontotemporal dementia with amyotrophic lateral sclerosis; HDLS, hereditary diffuse leukoencephalopathy with spheroids; CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; NMDARAE, N-methyl-D-aspartate receptor antibody encephalitis; VGKCAE, voltage-gated potassium channel antibody encephalitis; CNS, central nervous system.



Lewy Body Dementia

Lewy body dementia is the second most frequent cause of dementia in the elderly (see Chapter 52), characterized clinically by parkinsonism, hallucinations, and fluctuations in level of consciousness. Pathologically, the presence of Lewy bodies with molecular composition principally alpha-synuclein has led to the term synucleinopathy.


Frontotemporal Dementias

Frontotemporal dementias represent a molecularly heterogeneous group of degenerative disorders marked by frontal and temporal degeneration (see Chapter 51). Frontotemporal degeneration often presents with onset of symptoms at younger ages, in the 50s, and accounts for 5% to 10% of cases. Manifestations typically consist of either frontal-type behavioral disturbances (e.g., disinhibition, apathy, social impropriety, obsessions) or language disturbances. The molecular pathologies of this group of disorders can be broadly divided into those involving tau and those involving TDP-43 protein (TAR DNA-binding protein 43), with less common involvement of FUS, CHMP3, or VCP proteins. Pathologic entities including Pick disease, progressive supranuclear palsy, corticobasal degeneration, tangle dominant dementia, and argyrophilic grain disease are marked by prominent tau abnormalities and all now termed tauopathies. Motor neuron disease with dementia (amyotrophic lateral sclerosis dementia), some progressive aphasic disorders, and some behavioral variant frontotemporal dementias are TDP-43 proteinopathies.








TABLE 11.2 Prevalence of Dementing Disorders in the Elderly




















Alzheimer disease*


65%-85%


Lewy body disorders


15%-30%


Frontotemporal dementias


5%-10%


Vascular dementias


2%-10%


Other dementias


5%-10%


* Note that Lewy bodies may also be present in 20%-40% of cases.
Note that concomitant Alzheimer disease is present in 65%-90% of cases.
Note that infarcts are noted in ˜35% of cases of dementia.



Less Common Neurodegenerative Dementias

Other degenerative dementias include Wilson disease (see Chapter 134), a genetic disorder marked by copper deposition in the basal ganglia, dementia, and tremor, and Huntington disease (see Chapter 82), a genetic disorder marked by bicaudate atrophy, clinical dementia, chorea, and gait disorder. Even less frequent neurodegenerative dementing disorders include CJD (see Chapter 68), British familial dementia, neuroaxonal dystrophy, certain spinocerebellar ataxias, fragile X tremor ataxia syndrome, and others.


VASCULAR DEMENTIA

Cerebrovascular disease was once considered to be a major cause of dementia of the elderly but is now recognized to be the principle cause of dementia in less than 5% of cases in the United States. Syndromes of strategic infarct dementia, multiple infarct dementia, severe ischemic white matter disease (Binswanger disease or subcortical arteriosclerotic dementia), and hemorrhagic brain disease may all cause dementia (see Chapter 53). Acute stroke is a common cause of cognitive impairment but does not present as a gradually progressive dementing illness; instead, cognitive deficits follow in the aftermath of acute focal neurologic deficits or may take a stepwise course with discrete episodes of impairment and disability.


STRUCTURAL CAUSES OF DEMENTIA

The most common structural causes of dementia are chronic subdural hematoma (see Chapter 46) and hydrocephalus (see Chapter 106). Both diagnoses are established, in part, by neuroimaging, such as computerized tomography or magnetic resonance imaging, although imaging itself is not sufficient to determine the role of hydrocephalus in dementia. Subdural hematoma
typically presents as progressive deterioration in cognition and gait over days to weeks. Headache and lateralized focal deficits may or may not be present. Hydrocephalus represents a relative increase in cerebrospinal fluid in the cranial vault, causing compressive dysfunction of descending cortical pathways and cortex itself. The symptoms classically involve gait disorder, urinary incontinence, and dementia. Risk factors for hydrocephalus include prior history of intracranial hemorrhage, head injury, or meningitis, although these may not be known. Radiologically, distinguishing ventricular enlargement due to hydrocephalus from ventricular enlargement due to brain atrophy can be challenging.

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Jul 27, 2016 | Posted by in NEUROLOGY | Comments Off on Dementia and Memory Loss

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