Cortical Dementias

By | March 6, 2016

Alzheimer’s Disease

Most cases of Alzheimer’s disease start after age 65, but an earlier onset is not infrequent. Although some authors consider “presenile” and “senile” clinical forms to be different diseases, most consider them the same disorder with varied age at onset. The characteristic general dementia syndrome has been described and includes the cortical signs (). The insidious onset and slowly worsening, relentless course are most characteristic and crucial in the diagnostic process. The early clinical phase () is now distinguished from a preclinical phase, with mild cognitive impairment being apparent only on testing, preservation of instrumental ADLs, and specific neuroimaging findings. They include 1) a “hippocampal type” of memory difficulty, which is not reliably aided by cues on memory testing and has a high number of intrusions and false recognitions; 2) language difficulties, including a fluent aphasia with anomia, paraphasic errors, and a tendency of the patient to perseverate; 3) the patient’s being able in many cases to retain the ability to recognize objects and to use them appropriately at a time when he or she can no longer name them accurately; and 4) agnosia for faces, including family faces in late stages of the disease. Gait disorder in the middle stages is also common, as well as frontal signs such as grasping and sucking reflexes, along with a change in muscular tone.

The neuropathology of this condition is its defining characteristic; its extent and severity correlate with the type and severity of the cognitive signs and symptoms. Cortical atrophy occurs, with widened sulci and ventricular enlargement. The most severe changes occur in the medial temporal lobe, including the hippocampus. Areas of association cortex in the parietotemporal lobes and, to a lesser degree, the frontal lobes are also involved. Characteristic microscopic findings are neuronal loss; synaptic loss, particularly in the cortex; senile plaques, with a core of amyloid peptide; neurofibrillary tangles, containing abnormally phosphorylated tau proteins; granulovacuolar degeneration of the neurons; and amyloid angiopathy. The location and abundance of microscopic findings determine the postmortem histological diagnosis of Alzheimer’s disease.

Several studies have supported the cholinergic deficit hypothesis in DAT, including specific degeneration of cholinergic neurons in the nucleus basalis of Meynert; decreases in acetylcholine and choline acetyltransferase concentrations in the brain; and observations about the role of cholinergic agonists and antagonists. Other hypotheses are suggested by the decrease in norepinephrine activity and, more recently, by reports of decreased levels of many neurotransmitters, including serotonin and the neuroactive peptides somatostatin and corticotropin. Evidence also indicates that the excitatory activity of L-glutamate plays a role in the pathogenesis of DAT. However, recent research suggests that vascular factors may play an important role in determining the presence and severity of the clinical symptoms of DAT.

Dementia With Lewy Bodies

Dementia with Lewy bodies is a condition of uncertain nosological status, with cortical signs suggesting DAT alongside the classic, extrapyramidal features of Parkinson’s disease. However, the typical neuropathological findings of DAT are much less common in this condition. The distinctive feature is the presence of Lewy bodies in the cortex, particularly in limbic areas, whereas in Parkinson’s disease they are typically found in subcortical regions. Some authors now include both dementia with Lewy bodies and Parkinson’s disease among the alpha-synucleinopathies on the basis of recent pathological findings. Mean age at disease onset varies between 60 and 80 years. Psychotic, hallucinatory syndromes and confusional states are com-mon and may be the presenting symptomatology. Other characteristics include relative preponderance of visuo-spatial and frontal lobe signs, clear day-to-day fluctuations in symptoms and cognitive performance, and episodes resembling acute confusional states with visual and auditory hallucinations and paranoid delusions. Depressive symptoms also occur frequently. Patients who have dementia with Lewy bodies have frequent falls and/or transient, unexplained episodes of loss of consciousness. They have a characteristic vulnerability to neuroleptics, which frequently exacerbate extrapyramidal dysfunction. Such reactions may be severe and may include acute episodes of rigidity, instability, and falls.

Frontotemporal Dementia

Frontotemporal dementia syndromes, often accompanied by cortical signs, are also the result of neurodegenerative diseases. The most characteristic features that distinguish frontotemporal dementia from DAT are personality changes and neuropsychiatric symptoms, which may be quite marked and precede the cognitive decline by several years. The psychiatric symptoms in frontotemporal dementia include marked irritability; poor judgment; defective control of impulses, including violent impulses in some cases; disinhibition; and a general disregard for the conventional rules of social conduct. Restlessness and hyperorality also have been reported. Social withdrawal or overt depression may be the first symptom in some patients.

Neuronal loss and gliosis in the frontotemporal areas define this type of neurodegenerative dementia. Pick’s disease, characterized by the presence of distinctive intra-neuronal Pick bodies and ballooned Pick cells on microscopic examination, may be diagnosed in up to 2 5% of cases. This disease and the remaining types of frontotemporal dementias tend now to be classified as tauopathies, with a large clinical spectrum including Pick’s disease, PSP, cor-ticobasal degeneration, and multisystem atrophy. PSP is often classified among subcortical dementias because of the predominance of subcortical signs. Primary progressive aphasia is an atypical dementia typified by insidious and progressive impairment in language, with relative preservation of memory and other cortical functions, once thought to be rare but now recognized as not uncommon.

 

Selections from the book: “Textbook of Psychosomatic Medicine”, 2005.