Approach to the Patient with Dementia



Approach to the Patient with Dementia


Nilüfer Ertekin-Taner

Neill R. Graff-Radford



In the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria, dementia is defined as a decline in memory and at least one other cognitive function (aphasia, apraxia, agnosia, or a decline in an executive function, such as planning, organizing, sequencing, or abstracting). This decline impairs social or occupational functioning in comparison with previous functioning. The deficits should not occur exclusively during the course of delirium and should not be accounted for by another psychiatric condition, such as depression or schizophrenia. Dementia is further defined by a possible, probable, or definite etiologic diagnosis. The DSM-IV definition of dementia harbors the caveats that it may exclude debilitating cognitive disorders with predominant nonmemory presentation. Furthermore, minimally demanding environments may mask diagnosis of dementia.


I. EPIDEMIOLOGY OF DEMENTIA

It is estimated that the worldwide prevalence of dementia in 2010 is 4.7% in people aged >60, amounting to >35 million patients. The prevalence estimates vary from 2.6% in Africa to 6.5% in the Americas. The two most common types of dementia are Alzheimer’s disease (AD) and vascular dementia (VaD), accounting for 50% to 75% and 15% to 25% of all dementia cases, respectively. The global incidence of dementia is estimated to be approximately 7.5 per 1,000 population, increasing exponentially from 1 per 1,000 person years for ages 60-64 to >70 per 1,000 person years in 90+ year olds. The number of people with dementia is expected to increase to 65.7 million in 2030 and 115.4 million in 2050, unless new therapies that delay its onset or progression are developed. Thus, the public and socioeconomic impact of dementia is a significant worldwide problem.


II. RISK FACTORS AND ETIOLOGY


A. Risk factors.

The following have been identified as risk factors for the development of dementia and/or AD in one or more studies: Nonmodifiable risk factors proposed for dementia and/or AD are increasing age, female sex, unfavorable perinatal conditions, early life development, and growth. Modifiable risk factors fall into vascular and psychosocial categories. According to the vascular hypothesis, the following are modifiable risk factors for dementia: hypertension, obesity, hyperlipidemia, diabetes mellitus, heart disease (peripheral atherosclerosis, heart failure, and atrial fibrillation), cerebrovascular disease, heavy alcohol intake, and cigarette smoking. According to the psychosocial hypothesis, the following may be the socioeconomically modifiable risk factors for dementia: low education, poor social network, low mental or physical activity. The following have been proposed as potential protective factors for dementia, although their roles are yet to be proven in clinical trials: Statins, B group vitamins, “Mediterranean diet,” nonsteroidal anti-inflammatory agents, antioxidants, omega 3 fatty acids, physical and mental exercise, and treating sleep disorders.


B. Etiology.

Table 2.1 lists many of the causes of dementia. Potentially reversible conditions were identified in 4% to 8% of dementia cases in different studies. Hydrocephalus, space-occupying lesions, psychiatric disease, medications, alcoholism, and substance abuse were the most frequent causes of nondegenerative and nonvascular dementia. Although treatment for the potentially reversible conditions may not lead to partial or full reversal of dementia, their identification and attempted treatment is crucial.
Table 2.2 lists the degenerative causes of dementia by pathologic classification. Table 2.3 includes the syndromic classification of degenerative dementias. It is important to acknowledge that the same underlying pathology may present as different clinical syndromes, and different pathologies may present as the same clinical syndrome. Despite this, the existing clinicopathologic correlations allowed for the development of diagnostic criteria for degenerative and VaDs, discussed below.








TABLE 2.1 Causes of Dementia



















































































































Degenerative (see Tables 2.2 and 2.3)


Vascular


Multiple infarction


Single stroke


Binswanger’s disease


Vasculitis


Subarachnoid hemorrhage


Amyloid angiopathy


Hereditary cerebral hemorrhage



with angiopathy-Dutch type


CADASIL


Subdural hematoma


Infectious


Meningitis (fungal, mycobacterial, and bacterial)


Syphilis


AIDS dementia


Creutzfeldt-Jakob’s disease


Post-herpes simplex encephalitis


Lyme’s disease


Whipple’s disease


Progressive multifocal



leukoencephalopathy


Autoimmune/inflammatory


Systemic lupus erythematosus


Sögren’s disease


Multiple sclerosis


Steroid responsive encephalopathy


Paraneoplastic


Tumors


Glioblastoma


Lymphoma


Metastatic tumor


Toxic/metabolic


Vitamin B12 deficiency


Thyroid deficiency


System failure: liver, renal, cardiac, and respiratory


Heavy metals


Toxins (e.g., glue sniffing)


Electrolyte abnormalities


Hypoglycemia


Parathyroid disease


Drugs


Alcohol


Traumatic


Closed head injury


Open head injury


Pugilistic brain injury


Anoxic brain injury


Psychiatric


Depression


Personality disorder


Anxiety disorder


Other


Symptomatic hydrocephalus


Italics indicate the etiologic factor is at least partially reversible or treatable.









TABLE 2.2 Degenerative Dementias: Pathologic Classification













































































Amyloid/tau


AD


Tau



Pick’s disease



Corticobasal degeneration



Progressive supranuclear palsy



Frontotemporal dementia with parkinsonism




linked to chromosome 17 (tau mutations)



Tangle-only dementia



Argyrophilic grain disease


α-synuclein



Lewy’s body disease



Parkinson’s disease dementia



Multisystem atrophy


Tau-/Ubiquitin+



TDP-43+



FTLD with ubiquitin (FTLD-U) ± motor neuron




disease (±progranulin, valosin containing protein mutations)



TDP-43-



Neuronal intermediate filament inclusion disease



Basophilic inclusion body disease



FTLD-U with CMP2B mutation


Other



Huntington’s disease



Dementia lacking distinctive histologic features



Progressive subcortical gliosis










TABLE 2.3 Degenerative Dementias: Syndromic Classification









































MCI (progressive amnestic syndrome)



Single domain




Amnestic




Non-amnestic



Multiple domain




Amnestic




Non-amnestic


Frontotemporal dementia


PPA



Progressive nonfluent aphasia



Semantic dementia and associative agnosia


Corticobasal degeneration syndrome


Posterior cortical atrophy



III. CRITERIA FOR DIAGNOSIS

The following are the diagnostic guidelines for AD, VaD, dementia with Lewy’s bodies (DLB), and frontotemporal lobar degeneration (FTLD) (the four most common causes of dementia in order). Also presented are the guidelines for diagnosis of mild cognitive impairment (MCI), which bridges the spectrum between dementia and normal cognition.


A. Alzheimer’s disease.

AD is characterized by both amyloid and tau pathology. The National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s and Related Diseases Association 1984 criteria for the diagnosis of AD have recently been modified to take into account (1) Patients with the pathophysiologic process of AD, which can be found in those with normal cognition, MCI, and AD. This pathophysiologic process designated as AD-P is thought to begin years before the diagnosis of clinical AD. (2) The diagnostic criteria of other diseases such as Lewy’s body disease and frontotemporal dementia. (3) MRI, positron emission tomography (PET) for imaging the amyloid beta protein (Aβ), 18fluorodeoxyglucose (FDG) PET, and the CSF biomarkers A/42, total tau and phophotau. (4) Other clinical syndromes that do not present with amnesia but are related to AD pathology including posterior cortical atrophy and logopenic aphasia. (5) The dominantly inherited AD causing mutations in amyloid precursor protein, presenilin-1, and presenilin-2 (APP, PSEN1, PSEN2, respectively). (6) A change in age cut-offs noting persons under 40 and over 90 may have the same AD-P. (7) Many persons with possible AD in the past are now designated MCI.

Below we present the 1984 criteria for probable and possible AD. Patients who meet the 1984 criteria for probable AD still meet criteria for probable AD. Additionally, we present the proposed new 2011 criteria for AD in III.A.8.


1. Criteria for the clinical diagnosis of probable AD.



  • Dementia established by means of clinical examination and documented with the Mini-Mental State Examination, Blessed Dementia Rating Scale, or other similar examination and confirmed with neuropsychological tests.


  • Deficits in two or more areas of cognition.


  • Progressive worsening of memory and other cognitive function.


  • No disturbance of consciousness.


  • Onset between the ages of 40 and 90 years, most often after 65 years.


  • Absence of systemic disorders or other brain diseases that in and of themselves could account for the progressive deficits in memory and cognition.


2. Supporting findings in the diagnosis of probable AD.



  • Progressive deterioration of specific cognitive functions such as aphasia, apraxia, or agnosia.


  • Impaired activities of daily living and altered patterns of behavior.


  • Family history of similar disorders, particularly if confirmed neuropathologically.


  • Laboratory results as follows:



    • Normal results of lumbar puncture (LP) as evaluated with standard techniques.


    • Normal or nonspecific EEG changes (increased slow-wave activity).


    • Evidence of cerebral atrophy at CT with progression documented by means of serial observation.


3. Other clinical features consistent with the diagnosis of probable AD, after exclusion of causes of dementia other than AD.



  • Plateaus in the course of progression of the illness.



  • Associated symptoms of depression; insomnia; incontinence; delusions; illusions; hallucinations; catastrophic verbal, emotional, or physical outbursts; sexual disorders; and weight loss.


  • Other neurologic abnormalities for some patients, especially those with advanced disease, and including motor signs such as increased muscle tone, myoclonus, or gait disorder.


  • Seizures in advanced disease.


  • CT findings normal for age.


4. Features that make the diagnosis of probable AD uncertain or unlikely.



  • Sudden, apoplectic onset.


  • Focal neurologic findings such as hemiparesis, sensory loss, visual field deficits, and incoordination early in the course of the illness.


  • Seizures or gait disturbance at the onset or early in the course of the illness.


5. Clinical diagnosis of possible AD.



  • May be made on the basis of the dementia syndrome, in the absence of other neurologic, psychiatric, or systemic disorders sufficient to cause dementia and with variations in onset, presentation, or clinical course.


  • May be made in the presence of a second systemic or brain disorder sufficient to produce dementia, which is not considered to be the principal cause of the dementia.


  • Should be used in research studies when a single, gradually progressive, severe cognitive deficit is identified in the absence of any other identifiable cause.


6. Criteria for the diagnosis of definite AD

are the clinical criteria for probable AD and histopathologic evidence obtained from a biopsy or autopsy.


7. Classification of AD for research purposes

should specify features that differentiate subtypes of the disorder such as familial occurrence, onset before 65 years of age, presence of trisomy 21, and coexistence of other relevant conditions such as Parkinson’s disease.


8. Proposed new criteria for AD.

In 2011, National Institute on Aging and the Alzheimer’s Association workgroup suggested new criteria for AD based on clinical and research evidence. All patients who met the 1984 criteria for probable AD described in III.A.1 would meet the current criteria. In addition, the following criteria are proposed:

Aug 18, 2016 | Posted by in NEUROLOGY | Comments Off on Approach to the Patient with Dementia

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