Alzheimer's disease and dizziness

Timothy C. Hain, MD • Most recent update: July 19, 2020

This is a focused review of AD, concentrating on the aspects that are associated with dizziness.

In 1907, Alois Alzheimer reported the first case of Alzheimer's disease (AD). Alzheimer's disease probably accounts for 50-60% of cases of dementia in elderly patients. It affects an estimated 4 million persons in the United States. Dementia as well as other degenerative and hereditary central nervous system diseases are the 15th leading cause of disability adjusted life years in the United States (JAMA 285:5:2001).

In spite of an immense amount of research and money targeted at understanding and treating AD, so far, nothing has been shown to work. Many large drug companies have recently "pulled out" of development of drugs for AD, presumably due to futility.

Fortunately, recent research has suggested that dementia is going down modestly. Derby et al (2017) reported that in a sample of 1348 individuals in the Einstein Aging study, that the incidence of dementia decreased among those born after July, 1929. They review other large studies and note that they also note a decrease in dementia rates. The Rotterdam study reported a 25% decrease in all cause dementia rates betwen 1990 and 2000. The Framingham cohort also noted a 20% decrease in dementia incidence rates since the 1970's, in those older than 60 years. This is in spite of the greatly increasing prevalence of diabetes in the same age cohort.


The presentation of AD is variable and includes impairment of memory, language, visual function, and activities of daily living.

Criteria for diagnosis (NINCDS-ADRDA)

At present, there is no blood test or brain scan that will diagnose AD, and therefore all clinical diagnoses of AD must be considered possible or probable. "Definite AD" can be diagnosed only by brain biopsy or autopsy. Recently it has been reported that improved discrimination of AD from other neurological diseases can be accomplished using a test for amyloid and tau proteins in spinal fluid. Amyloid-beta42 is low and Tau is high. CSF Tau increases early in AD and appears to be stable (Andreasen et al, 1999).

Recently, a test for cerebral amyloid using PET scanning (which is very expensive) was tested by Jack et al (2019). This test is not expected to be clinically important, as the value of adding this test to other clinical and genetic variables was "small". (Jack et al, 2019)

Takeda et al (2016) reported that tau in AD patients is "seed-competent", which seems to us to suggest that it might be a prion, and perhaps making AD similar to Creutzfeldt-Jakob/Mad Cow disease.

A partial list of other types of dementia that need to be excluded before making a diagnosis of AD includes most pathologic processes that affect the brain:

Many of these can be excluded easily from the examination combined with neuroimaging such as a CT scan or MRI.

Pick's disease (also called frontotemporal dementia or FTD) is characterized by disordered initiation, goal-setting and planning (i.e. executive function) with apathetic or disinhibited behavior. Cognitive testing may be minimally impaired. FTD, like MSA and PSP are characterized by neuronal inclusions of Tau.

Creutzfeldt-Jakob, is rare with an incidence of roughly 1/million. It follows a rapid course and can be transmitted. It is caused by small protein agents called prions. Similar agents are thought to cause "mad cow disease". Increased levels of CSF tau have also been reported in this disorder.

Vascular dementia can follow multiple strokes. There is accumulation of lesions from strokes causing a variable presentation.

Pathophysiology of AD:

Neuropathologic changes begin in persons in the late 20's and 30's, slowly progress and often manifest as mild cognitive impairment.

Amyloid plaques and neurofibrillary tangles (containing Tau) are the hallmark of the disease. Generation of amyloid-beta (AB) occurs normally throughout life. y-secretase is an enzyme that cleaves amyloid into "monomers". The "amyloid hypothesis" of AD says that AD is caused by an imbalane between production and clearance of AB, which leads to accumulation in brain regions and toxicity. Persons who develop AD are believed to have larger amounts of AB monomers and dimers. AB monomers and dimers are thought to impair processes related to thinking, especially dimers (Shankar et al, 1999)

There are rare familial variants of AD, often associated with a high frequency of apoliproprotein E4 alleles. Apolipoprotein E appears to be involved with repair processes in the CNS, and the E4 allele reduces the efficiency of repair. Other genes involved with AD are the PS1 (presenilin) gene on chromosome 14 and the APP (amyloid precursor protein) gene.

The presenilin gene is responsible for the y-secretase enzyme, that produces AB. Mutations in presenilin can result in a more aggressive form of AD.

While there was initially some enthusiasm it is no longer felt that mitochondrial gene mutations are significant in AD(Davis et al, PNAS 1997:94:4526-4531).

A common final common pathway for these toxic genes may be free radical generation and apoptosis. Still, the problem is upstream and any treatment aimed at free radicals or apoptosis is likely to fail.

How does AD cause dizziness ?

Unlike many other degenerative dementias, AD is not particularly associated with dizziness. This is because AD mainly affects the cortex and does not typically cause either low blood pressure (such as is seen in MSA), basal ganglia feature (e.g. PSP), or slow eye movements (e.g. PSP). Dizziness from AD instead typically might include falls due to:

Alzheimer's is a "anything goes" type dementia and one can certainly attribute dizziness to AD. Posterior cortical atrophy, for example, is defined as shrinkage of the visual part of the brain, due to whatever cause, but mainly Alzheimer's disease, as AD is a major cause of cerebral atrophy. Posterior cortical atrophy is described in an open journal here.


Treatment of AD

Treatment of AD is largely supportive. This is probably related to the present impossibility of reversing neural damage that has been gradually accumulating over decades. There are several cholinergic agonists on the market that have a small effect.

There are an immense number of papers concerning dubious treatments, diets, and procedures to prevent AD.

A diet high in mono-unsaturated fatty acids (such as olive oil) may protect somewhat against age-related cognitive decline (Sofrizzi et al, 1999).

Mice that were exposed to "environmental enrichment -- i.e. cages with toys and running wheels", prevented the toxic effect of human brain extracts on their thinking. Also, protection was as seen when a beta-agonist was given.

Cholinesterase inhibitors -- increase the amount of acetylcholine, and slightly improve memory and thinking.

Memantine (Namenda) -- reduces glutamate mediated excitotoxicity.

Antipsychotic agents -- reduces thought disorders

PPI drugs -- avoid.

Gomm et al (2016) reported that "regular" use of proton pump inhibitor PPI drugs increased the risk of AD with a hazard ratio of about 1.44. This was a very large study done in Germany. The authors did not prove a mechanism, but offered several hypotheses. Given this large study, and the rather large effect, in spite of not knowing the reason, we think it prudent to avoid PPI when feasible.


In mice, monthly injections of AB into APP transgenic mice cleared plaque (? immunotherapy ?) (Schenk, 1999). Passive anti-AB immunotherapy slows down cognitive decline (Lily study). In the Biogen study, amyloid plaque reduced but there was no improvement in cognitive status.