In Alzheimer's disease (AD), defects in essential metabolic processes for energy supply and phospholipid membrane function have been implicated in the pathological process. However, post-mortem investigations are generally limited to late stage disease and prone to tissue decay artifacts. In vivo assessments of high energy phosphates, tissue pH and phospholipid metabolites are possible by phosphorus MR spectroscopy (31P–MRS), but so far only small studies, mostly focusing on single brain regions, have been performed. Therefore, we assessed phospholipid and energy metabolism in multiple brain regions of 31 early stage AD patients and 31 age- and gender-matched controls using 31P–MRS imaging. An increase of phosphocreatine (PCr) was found in AD patients compared with controls in the retrosplenial cortex, and both hippocampi, but not in the anterior cingulate cortex. While PCr/inorganic phosphate and pH were also increased in AD, no changes were found for phospholipid metabolites. This study showed that PCr levels are specifically increased in regions that show early degeneration in AD. Together with an increased pH, this indicates an altered energy metabolism in mild AD.

Cerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled study investigated how 6 months of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mild-to-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest including the hippocampus. Fifty-eight patients were randomly assigned (29 in each group), of whom 22 in both groups had no magnetic resonance exclusion criteria and were medication compliant over 6 months. Mean age was 72.8±6.2 years, mean mini-mental state examination was 20.4±3.4. Nilvadipine treatment lowered systolic blood pressure (Δ=−11.5 [95% CI, −19.7 to −3.2] mm Hg; P <0.01), while whole-brain gray-matter CBF remained stable (Δ=5.4 [95% CI, −6.4 to 17.2] mL/100 g per minute; P =0.36). CBF in the hippocampus increased (left: Δ=24.4 [95% CI, 4.3–44.5] mL/100 g per minute; P =0.02; right: Δ=20.1 [95% CI, −0.6 to 40.8] mL/100 g per minute; P =0.06). There was no significant change in CBF in the posterior cingulate cortex (Δ=5.2 [95% CI, −16.5 to 27.0] mL/100 g per minute; P =0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressure and increased CBF in the hippocampus, whereas other regions showed stable or small nonsignificant increases in CBF. These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02017340.