Age is a risk factor for AD. The prevalence of AD doubles every five years after the age of 60.
A family history of AD is a consistent risk factor, and represents around a fourfold increase in the risk of developing the disease. It is thought that as many as 33% of all cases of AD may be familial.
A link has been established between the frequency of a specific allele, apolipoprotein E4 (ApoE4), and the occurrence of AD. The presence of the ApoE4 allele increases the probability that the patient with dementia has AD. The absence of the ApoE4 allele makes this less likely. Although there is a strong link between ApoE4 and AD, not everyone who carries the allele develops AD. Conversely, not all AD patients carry the allele. So despite the fact that ApoE4 is a risk factor for AD in some patients, it is not suitable for routine use as a diagnostic marker for AD.
Other risk factors
Gender appears to be a risk factor, women being at greater risk of developing AD than men. The higher prevalence of AD among women is probably due to a longer life expectancy. Repeated head trauma also increases the risk of developing AD. The presence of vascular disease is a potential risk factor. All individuals with Down’s syndrome develop the characteristic neuropathological features of AD by the age of 40, although many do not demonstrate the clinical symptoms of dementia.
Neuropathology of AD
The most characteristic neuropathological features (Table 5) are amyloid (senile) plaques and neurofibrillary tangles (NFTs). Amyloid protein is believed to play an important role in the pathogenesis of AD and may be critical for the formation of the amyloid or senile plaques in the brain. These plaques seem to reflect damage in the surrounding nerve endings. This damage to the neurons causes impaired neurotransmission and results in the cognitive deficits observed with AD.
Although NFTs are also a characteristic finding in the brain they are not specific to AD and are found in several other degenerative dementing disorders. NFTs contain paired helical filaments (PHFs) which are composed of abnormal microtubule-associated proteins (tau protein). In AD, abnormal phosphorylation of the tau protein results in aggregation of PHFs to form the NFTs. The definite diagnosis of AD relies on the presence of sufficient numbers of both amyloid plaques and NFTs at autopsy or via biopsy.
* Neurofibrillary tangles
* Senile (amyloid) plaques
* Neuronal loss
* Cortical and central atrophy
Many areas of cognition are compromised in AD. In the early stages, in particular, memory, language and frequently visuospatial abilities are affected.
Memory is a complex function and, in simple terms, is made up of a temporary store (short-term or primary memory) and a permanent store (long-term memory). Short-term memory describes the ability to learn and briefly retain information. This area of memory is generally not substantially affected by age. Long-term memory, particularly retrieval, the ability to learn information and retain it for longer periods, however, begins to decline at the age of 50 as part of the normal aging process. In AD, short-term memory is affected, first causing difficulties in learning and recalling new information. Patients may fail to remember a recent conversation or a telephone number long enough to repeat it. Remote (biographical) memory is usually not affected until late into the disease.
The initial, characteristic cognitive feature of AD is progressive loss of memory. This decline in memory often triggers the patient or family member to seek help from a physician.
Two important aspects of memory retrieval are affected: recall (e.g. remembering a street or person’s name) and recognition (e.g. recognizing a street or person’s name). The ability to remember general information, such as the names of capital cities or the president/premier, is also affected. Remembering how to perform tasks, procedural memory, is not altered in the early stages of AD. As the disease progresses, short-term memory is dramatically compromised, and long-term memory also fades.
Language impairment (aphasia) is a common feature of AD. Difficulty in finding words in spontaneous speech and the ability to name objects are affected first. Although the ability to construct sentences is initially retained, they become less complex. Patients may experience great difficulty in remembering and using appropriate words. As the disease progresses, word pronunciation also deteriorates.
Although decline in visuospatial awareness is part of normal aging, it may be exacerbated in AD. Patients with AD may experience difficulty driving the car, finding their way in the home or may put clothing on back-to-front. Visuospatial awareness can be tested by asking the patient to copy/draw and recognize two- and three-dimensional figures and objects.
Functional ability is usually separated into two categories: self-maintenance skills or Activities of Daily Living (ADLs), and the more complex higher-order skills, Instrumental Activities of Daily Living (IADLs). Decline in functional ability is linked to cognitive decline and can be correlated to a decline in MMSE (Table 6). Changes in functional ability are often the first indication that a dementing illness is present. Functional decline in AD causes considerable concern for both the sufferer and caregivers. IADLs are usually affected first, with ADLs affected later in the disease.
Deterioration in social and occupational activities is a characteristic clinical feature of AD. Initially in AD, the inability to carry out normal IADL tasks is diminished. Patients have problems driving the car, paying bills or functioning at work. As the disease progresses, more basic ADL tasks, the basic living skills, are affected. The ability to perform tasks; personal care, bathing, eating, etc, becomes restricted.
Changes in behavior are common in AD and include mood swings, aggression, agitation and disinhibition. These changes are distressing both for the patient and family and are often difficult to come to terms with.
At the onset of the illness, family members may report changes in personality. Patients exhibit increased irritability, a lack of enthusiasm, unhappiness, unreasonable behavior, a loss of sensitivity. Many sufferers become agitated or wander.
Symptoms of depression and anxiety as well as psychiatric phenomena such as delusions or hallucinations may often be present. Symptoms of depression and anxiety may initially accompany AD. Depression may be difficult to distinguish from apathetic states related to AD. Paranoid delusions are common, leading to, for example, accusations of theft or a fear of unknown intruders.
Developed from scientific presentations at a special IPA meeting.
Sponsored by an educational grant from Pfizer Inc and Eisai Ltd.
International Psychogeriatric Association